Enhanced dissolution of sildenafil citrate as dry foam tablets

Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5?kg, friability test <1% with a disintegration time <5?min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.     

Extraintestinal manifestation of inflammatory bowel disease in Asian patients: A multinational study

Background/aimAlthough inflammatory bowel disease (IBD) incidence has increased over the past two decades in Asia, data on extraintestinal manifestations (EIMs) of IBD in Asian patients are limited. We aimed to evaluate the prevalence and clinical characteristics of EIMs in Asian IBD patients.MethodsIn total, 1,764 patients (1,130 with ulcerative colitis [UC] and 634 with Crohn's disease [CD]) were recruited from 10 tertiary centers in Asia. The medical records of IBD patients were retrospectively reviewed for the presence, clinical characteristics, chronological order, and therapeutic management of EIMs.ResultsEIMs were reported in 199 (11.3%) patients, of which 17 (1.0%) patients had multiple EIMs. EIMs were more prevalent in CD patients (P = 0.02). Multiple logistic regression analysis revealed that female sex (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.15–3.55), stricture (OR 2.49, 95% CI 1.41–4.39) and female sex (OR 2.57, 95% CI 1.52–4.34), extensive colitis (OR 2.63, 95% CI 1.57–4.41) were associated with EIMs in CD and UC patients respectively. EIMs appeared in 8% of patients before IBD diagnosis; 95% of cases with EIM could be managed via first-line therapy.ConclusionEIM prevalence is lower among Asian IBD patients than among patients from Western countries; however, the risk factors for EIM were similar between both populations.     

The presence and distribution of gonadotropin-releasing hormone-liked factor in the central nervous system of the black tiger shrimp, Penaeus monodon

The distribution and presence of gonadotropin-releasing hormone (GnRH) in the central nervous system (CNS) of Penaeus monodon were examined by immunocytochemistry, high performance liquid chromatography (HPLC), and radioimmunoassay (RIA). We demonstrated the existence of octopus (oct)GnRH-liked immunoreactivity (ir-octGnRH) and lamprey (l)GnRH-III-liked immunoreactivity (ir-lGnRH-III) in cell bodies of medium-sized neurons of the anterior part (protocerebrum) of the supraesophageal ganglion (brain). In addition, only the ir-octGnRH was detected in the nerve fibers located in the brain and segmental ganglia (subesophageal, thoracic, and abdominal ganglia). Moreover, some branches of these fibers also innervated the neurons in the middle (deutrocerebrum), posterior (tritocerebrum) brain and segmental ganglia. There was no ir-lGnRH-I and ir-salmon (s)GnRH detected in the shrimp CNS. The results from HPLC and RIA showed ir-GnRH in the CNS using anti-lGnRH-III, but not with anti-mammalian (m)GnRH. The data from immunocytochemistry, HPLC and RIA suggest that ir-GnRH in shrimp may be more similar to octGnRH and lGnRH-III than the other forms. These findings support the hypothesis that GnRH-liked factor(s) may be an ancient peptide that also exists in this decapod crustacean.     

A newly recognized polyosteolysis/hyperostosis syndrome

We report a newly recognized bone disorder consisting of polyostotic expansile osteolysis affecting long bones and iliac bones; hyperostosis of the skull, thoracic cage, and medial portion of both clavicles; pectus carinatum; gigantiform synovial masses of the elbows and knees; atrial septal defect; cardiomegaly; unilateral cryptorchidism; and mental deficiency. Affected bones can be grouped into four general types of skeletal pathology: (1) expansile osteolysis, (2) osteolysis without expansion, (3) expansion without osteolysis, and (4) hyperostosis. Some bones remained unaffected. We have named the condition "polyosteolysis/hyperostosis syndrome." It is clearly at variance with any previously reported bone disorder, including familial expansile osteolysis, juvenile Paget disease, and McCune-Albright syndrome (and polyostotic fibrous dysplasia). Because our patient shared some features in common with juvenile Paget disease, we thought that mutational analysis of TNFRSF11B was indicated, even though our patient had some manifestations not found in juvenile Paget disease. Direct sequencing failed to identify a TNFRSF11B mutation. Because the parents of our propositus were first cousins suggests that polyosteolysis/hyperostosis syndrome may possibly have autosomal recessive inheritance.     

Feasibility Study on Computer-Aided Screening for Diabetic Retinopathy

Purpose

To conduct a feasibility study of computer-aided screening for diabetic retinopathy by developing a computerized program to automatically detect retinal changes from digital retinal images.

Methods

The study was carried out in three steps. Step 1 was to collect baseline retinal image data of 600 eyes of normal subjects with normal fundi and data of 300 eyes of diabetic patients with diabetic retinopathy. All data were recorded by digital fundus camera. Step 2 was to analyse all retinal images for normal and abnormal features. By this method, the automated computerized screening program was developed. The program preprocesses colour retinal images and recognizes the main retinal components (optic disc, fovea, and blood vessels) and diabetic features such as exudates, haemorrhages, and microaneurysms. All of the accumulated information is interpreted as normal, abnormal, or unknown. Step 3 was to evaluate the sensitivity and specificity of the computerized screening program by testing the program on diabetic patients and comparing the program's results with the results of screening by retinal specialists.

Results

Diabetic patients (182 patients, 336 eyes) were examined by retinal specialists; 221 eyes had a normal fundus and 115 eyes had nonproliferative diabetic retinopathy. Digital retinal images were taken of these 336 eyes and interpreted by the automated screening program. The program had a sensitivity and specificity of 74.8% and 82.7%, respectively.

Conclusions

The automated screening program was able to differentiate between the normal fundus and the diabetic retinopathy fundus. The program may be beneficial for use in screening for diabetic retinopathy. Further development of the program may provide higher sensitivity.?Jpn J Ophthalmol 2006;50:361–366 © Japanese Ophthalmological Society 2006     

Differential effects of hydroxyacetophenone analogues on the transcytotic vesicular pathway in rat liver

Insertion of transporter proteins into the apical canalicular membrane via vesicular transport is one of several choleretic mechanisms. Based on different choleretic activities of hydroxyacetophenone analogues including 4-mono; 2,6-di and 2,4,6-trihydroxy-acetophenone (MHA, DHA and THA), the present study aims to determine if these compounds stimulated vesicular transport in hepatocytes. Hydroxyacetophenone was continuously infused into the duodenum of the bile fistula rat. Bile flow rate was allowed to stabilize and then followed by an intraportal injection of horseradish peroxidase, a marker of the transcytotic vesicle pathway. MHA which stimulates bile acid independent flow, showed a dose-dependent increase in both the early (paracellular) and late (transcellular) peak of horseradish peroxidase excretion in bile. THA, which stimulates both bile acid dependent flow and bile acid independent flow, did not alter the pattern of horseradish peroxidase excretion into bile. However, DHA, which is more hydrophobic and increases only bile acid dependent flow, decreased the late peak. The stimulating effects of MHA on bile flow and horseradish peroxidase excretion were markedly inhibited by colchicine, suggesting that its choleretic action involves stimulation of exocytosis, as well as increase in paracellular permeability. In contrast, the lack of a stimulatory effect of THA and DHA on biliary horseradish peroxidase excretion suggested that their choleretic action is not associated with vesicular exocytosis. These results demonstrate a variable effect of hydroxyacetophenones on the transcytotic vesicular pathway reflecting different choleretic mechanisms and therapeutic potential.