Objective: To prepare and optimize tilianin loaded solid lipid nanoparticles (T-SLNs), and investigate the physicochemical properties, absorption and transport behavour of T-SLNs in vitro. Methods: T-SLNs were prepared by high shear homogenization followed by ultrasonication and optimized by central composite design and response surface methodology. In the study, the physicochemical properties of T-SLNs including size, polydispersity (PDI), Zeta potential, shape, entrapment efficiency and release profile in vitro were investigated, the absorption and transport behavour of T-SLNs in Caco-2 cell model were also measured. Results: The optimum formulation of T-SLNs consisted of: drug/lipid of 0.11, soy lecithin/lipid of 1.26, and content of tween-80 was 5.05%. The prepared T-SLNs were spherical and uniform with the mean particle diameter at (86.40 ± 0.62) nm, PDI (0.165 ± 0.080) and Zeta potential of (-24.2 ± 0.6) mV, respectively. The average EE was (89.81 ± 1.07)%, and the release in vitro showed that tilianin was released about (98.72 ± 1.57)% in 48 h. Besides, the absorption and transport assays of T-SLNs in Caco-2 cells model indicated that T-SLNs had a higher absorption and transport than tilianin. Conclusion: The method of high shear homogenization followed by ultrasonication is suitable for T-SLNs preparation. The optimal T-SLNs have a smaller particle size and high EE. Moreover, in the same concentration of tilianin, the absorption and transport amounts of T-SLNs in Caco-2 cell model were higher than tilianin.

Cardiomyopathy, Hypertrophic ; complications ; Down Syndrome ; complications ; Humans ; Infant, Newborn ; Male

Forty-seven surgically confirmed cases of brain abscess treated from 1988 to 1992 are described. The most common cause was chronic ear infection with abscesses in the cerebellum and the temporo-parietal area. Patients in the second and third decade of life were most frequently affected. Clinical manifestation at the time of admission were headaches, vomiting and fever. Bacteriology revealed a predominance of microaerophilic streptococcus and staphylococcus aureus among the aerobes and peptostreptococcus sp. among the anaerobes. Majority were sensitive to Penicillin G and Chloramphenicol. Computerized tomographic scanning was the sole diagnostic procedure done with 100% accuracy. Excision was done on well encapsulated abscesses. The non-encapsulated ones were aspirated and drained. The overall mortality rate was 15 percent.(Author)

Human ; Male ; Female ; Middle Aged ; Adult ; Adolescent ; Child ; Child Preschool ; Infant ; Infant Newborn ; Staphylococcus Aureus ; Peptostreptococcus ; Brain Abscess ; Staphylococcal Infections ; Penicillin G ; Headache ; Otitis

INTRODUCTIONParacetamol is the most common pharmaceutical agent implicated in toxic exposure in Singapore. This study aimed to describe the characteristics of paracetamol overdose in the adult population managed at a tertiary healthcare facility in Singapore.

METHODSMedical records of adult patients hospitalised with a diagnosis of paracetamol overdose at National University Hospital, Singapore, over a three-year period from January 2011 to December 2013 were retrospectively reviewed.

RESULTSA total of 177 patients had paracetamol overdose. The median age was 25 years, with a significant female predominance (71.2%). Intentional ingestion accounted for the majority (76.8%) of cases. The median dose of paracetamol ingested was 10 (interquartile range 8-15) g. Among patients who reported ingesting more than 10 g, 46.5% perceived the overdose as non-lethal. N-acetylcysteine was administered in 76.3% of patients, among whom 24.4% experienced an anaphylactoid reaction. Of the 10 (5.6%) patients who had severe hepatotoxicity, 2 (1.1%) developed acute liver failure. Most patients had resolving transaminases at discharge and none required liver transplantation. The median length of hospitalisation was three days. There were no fatalities.

CONCLUSIONParacetamol overdose occurred predominantly in young adults with intentional ingestion, suggesting that preventive measures targeted at promoting public awareness may not suffice. However, the perceived lack of lethality by many patients who ingested potentially toxic amounts of paracetamol reflects a certain knowledge gap. Healthcare providers should proactively educate consumers on the proper use of paracetamol and the consequences of its overdose.

Astragalus polysaccharides was lounded to 4-(2-aminoethylphenol), followed by labeling the APS-Tyr with fluorescein-5-isothiocyanate (FITC) at the secondary amino group. The absorption enhancement effects of low molecular weight chitosan and protamine on astragalus polysaccharides were evaluated via Caco-2 cell culture model. The results show that the fluorecent labeling compound has good stability and high sensitivity. On the other hand low molecular weight chitosan and protamine also can promoted absorption of the astragalus polysaccharides without any cytotoxity, and the absorption increase was more significant with increasing the amount of low molecular weight chitosan and protamine. At the same time, the low molecular weight chitosan has slightly better effect. The transepithelial electric resistance (TEER) of Caco-2 cells show that absorption enhancers could improve its membrane transport permeability by opening tight junctions between cells and increasing the cell membrane fluidity.
Absorption ; Astragalus Plant ; chemistry ; Biological Transport ; Caco-2 Cells ; Fluorescein-5-isothiocyanate ; chemistry ; Fluorescent Dyes ; chemistry ; Humans ; Plant Extracts ; chemistry ; pharmacokinetics ; Polysaccharides ; chemistry ; pharmacokinetics

Introduction: HbE is the commonest beta haemoglovin (Hb) variant in Southeast Asia. It causes a reduction in synthesis of beta-globin E (βE) chain. Studies indicate HbE coinherited with α-thalassaemia leads to a milder clinical phenotype. This study investigates the concomitant inheritance of α-thalassaemia in Malays with HbE. Methods: Four hundred and fourteen (414) blood samples were screened for haemoglobinopathy using primarily the first 3 steps of the BHES [(B) blood counts, blood film: (H), HPLC; (E),elstrophoresis; (S),stability)] protocol. Complete blood counts were generated on an automated blood cell analyser, HB typing with cation exchange high-performance liquid chromatography (HPLC) and Hb typing with cation exchange high-performance liquid chromatography (HPLC) and Hb electrophoresis at an alkaline pH (pH 8.5). Forty-five (10.9%) were identified as HbE trait and DNA analysis was done for deletional α-thalassaemia using a single-tube multiplex-PCR assay. Results: Among the 45 subjects with HbE trait. 4 (8.9%) were found to have alpha-thalassaemia-2 (α⁺) (α-3.7 kb deletion) and 1 (2.2%) the alpha-thalassaemia-1 (α⁰) (—SEA 20.5kb deletion) defects respectively. Discussion: These findings show that 11.1% of Malays with HbE inherit alpha-thalassaemia concurrently. The most prevalent interaction found was a double heterozygote for HbE/α-thalassaemia 2, followed by HbE/α-thalassaemia 1. Conclusion: Molecular screening of deletional α-thalassaemia identified its concurrent inheritance in 11.1% of Malays who were HbE carriers. This information will guide genetic counseling and the planning of treatment modalities in patients with HbE alpha-thalassaemia.

Adult ; Hamartoma ; pathology ; Humans ; Liver ; pathology

Colorectal Neoplasms ; genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis ; metabolism ; DNA Mismatch Repair ; Humans ; Microsatellite Instability

INTRODUCTIONLower extremity amputation prevention (LEAP) is an ongoing programme in our institution aimed at limb salvage in patients with critical limb ischaemia (CLI). Patients in the LEAP programme with reconstructible anatomy on initial Doppler imaging received either bypass surgery or percutaneous transluminal balloon angioplasty (PTA). We describe the 1-year limb salvage rates in 46 consecutive patients with CLI who received PTA in 2005.

CLINICAL PICTUREA total of 46 patients, 28 women and 18 men, between the ages of 40 and 91 years old (mean age, 70.8) received PTA in 2005. The most common presenting symptom was rest pain (n = 23), followed by pre-existing gangrene (n = 20), non-healing ulcer (n = 17) and cellulitis (n = 8). The majority of the patients (57%) had 3 to 4 risk factors. Diabetes mellitus (91%) and hypertension (80%) were the 2 most common risk factors. The patients were kept under surveillance for periods ranging from 12 to 21 months with a mean of 13.3 months, both clinically and with haemodynamic measurements [ankle-brachial index (ABI), toe pressure (TP) and digital-brachial index (DBI)].

TREATMENTThe aim of PTA is to achieve straight-line flow from the abdominal aorta down to either a patent dorsalis pedis or plantar arch with limb salvage as the ultimate goal. The patterns of the treated segments were as follows: aorto-iliac occlusions (n = 3), pure infrapopliteal disease (n = 5), femoropopliteal disease with at least 1 good infrapopliteal run-off vessel (n = 16) and combined femoropopliteal and infrapopliteal disease (n = 25). Technical success was achieved in 89% of patients (41 out of 46 patients). The most common cause of technical failure is the inability to cross long chronic total occlusions.

OUTCOMEPaired T test was performed and showed statistically significant improvement in haemodynamic markers within the technically successful group. This included increase in the mean ABI from 0.62 (preangioplasty) to 0.91 (Day 1 post-angioplasty), an increase of 0.29 [95% confidence interval (95% CI), 0.1953 to 0.3875; P <0.001]. One year post-angioplasty, the mean ABI was 0.84, an increase of 0.22 (95% CI 0.1512 to 0.3121; P <0.001). There was also significant increase in the mean DBI of 0.17 from 0.23 to 0.41 (pre-angioplasty versus Day 1 post angioplasty - 95% CI of 0.1006 to 0.2433; P <0.001). In addition, significant increase in the mean TP of 28.2 mmHg from 36.8 to 63.2 mmHg (pre-angioplasty versus Day 1 post angioplasty - 95% CI, 18.493 to 37.939; P <0.001) was also noted. Of the 23 patients who presented with rest pain, total abolishment of symptoms was achieved in 21 patients (91%). Healing of pre-existing gangrene was attained in 15 patients (66%). Five patients subsequently received minor amputation for pre-existing gangrene. Clinical improvement in all the patients who presented with non-healing ulcers (n = 17) and cellulitis (n = 8) was attained. More importantly, all healed ulcers remained healed throughout the study period. The limb salvage rates were 93% at 1 month, 87% at 3 months, 82% at 6 months and 78% at 1 year.

CONCLUSIONAngioplasty is a safe and effective limb salvage method in patients with CLI and has a high 1-year limb salvage rate.

Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon ; Female ; Humans ; Ischemia ; physiopathology ; therapy ; Leg ; blood supply ; Limb Salvage ; Male ; Middle Aged ; Survival Analysis ; Treatment Outcome

Objective:RNA interference technology (siRNA) was used to inhibit the expression of DJ-1 gene in lung squamous cell carcinoma HTB-182 cells, then, tandem affinity purification mass spectrometry (TAP-MS) was performed to screen the interacting proteins of DJ-1 in lung cancer cell line of HTB-182.Methods:The siRNA lentivirus vector targeting DJ-1 gene was constructed to infect HTB-182 cells (DJ-1 siRNA group), and the lentivirus vector control group (control siRNA group) and blank control group were established. The expression level of DJ-1 protein was detected by Western blot, and the endogenous DJ-1 protein silenced si-DJ-1-HTB-182 cells were established. The specific primers of DJ-1 were designed, and the DJ-1 expression plasmid pNTAP-DJ-1 with streptomycin binding peptide label (SBP) and calmodulin binding peptide label (CBP) was constructed. The cell line DJ-1 siRNA HTB-182 was stably transfected with liposome, and the positive clones were screened by G418. The positive clones were verified by Western blot, and the interacting proteins of DJ-1 were found by TAP-MS.Results:The protein expression of DJ-1 in DJ-1 siRNA interference group was significantly lower than that in empty plasmid group and blank control group ( P<0.05); HTB182 cell line stably expressing pNTAP-DJ-1 plasmid was successfully constructed; Three proteins interacting with DJ-1 were screened by TAP-MS: cytokeratin 1 (keratin 1), cytokeratin 10 (keratin 10) and NADPH oxidase activating protein P47 (P47 Px). Conclusions:Keratin 1, Keratin l0 and P47 Px protein may be DJ-1 interactions protein.