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Biomedical subjects

S M Wong

Publications and source records attributed to S M Wong.

At least 19 recordsLinked to original sources

Enhancement of the dissolution rate and oral absorption of a poorly water soluble drug by formation of surfactant-containing microparticles.

The slow dissolution rate exhibited by poorly water-soluble drugs is a major challenge in the drug development process. Following oral administration, drugs with slow dissolution rates generally show erratic and incomplete absorption which may lead to therapeutic failure. The aim of this study was to improve the dissolution rate and subsequently the oral absorption and bioavailability of a model poorly water-soluble drug. Microparticles containing the model drug (griseofulvin) were produced by spray drying the drug in the absence/presence of a hydrophilic surfactant. Poloxamer 407 was chosen as the hydrophilic surfactant to improve the particle wetting and hence the dissolution rate. The spray dried particles were characterized and in vitro dissolution studies and in vivo absorption studies were carried out. The results obtained showed that the dissolution rate and absolute oral bioavailability of the spray dried griseofulvin/Poloxamer 407 particles were significantly increased compared to the control. Although spray drying griseofulvin alone increased the drug's in vitro dissolution rate, no significant improvement was seen in the absolute oral bioavailability when compared to the control. Therefore, it is believed that the better wetting characteristics conferred by the hydrophilic surfactant was responsible for the enhanced dissolution rate and absolute oral bioavailability of the model drug.

Animals↗

Hibiscus chlorotic ringspot virus p27 and its isoforms affect symptom expression and potentiate virus movement in kenaf (Hibiscus cannabinus L.).

Hibiscus chlorotic ringspot virus (HCRSV), a member of the genus Carmovirus, encodes p27 (27-kDa protein) and two other in-frame isoforms (p25 and p22.5) that are coterminal at the carboxyl end. Only p27, which initiates at the 2570CUG codon, was detected in transfected kenaf (Hibiscus cannabinus L.) protoplasts through fusion to a Flag tag at either its N or C terminus. Subcellular localization of a p27-green fluorescent fusion protein in kenaf epidermal cells showed that it was localized to membrane structures close to cell walls. To study the functions of these proteins, a number of start codon mutants and premature translation termination mutants were constructed. Phenotypic differences were observed between the wild-type virus and these mutants during infection. Infectivity assays on plants indicated that p27 is a determinant of symptom severity. Without p25, appearance of symptoms on systemically infected kenaf leaves was delayed by 4 to 8 days. In a timecourse analysis, Western blot assays revealed that the delay corresponded to retardation in virus systemic movement, which suggested that p25 is probably involved in virus systemic movement. Mutations disrupting expression of p22.5 did not affect symptoms or virus movement.

3' Untranslated Regions↗

Fast-dissolving microparticles fail to show improved oral bioavailability.

Oral dosage forms are the preferred means of delivering drugs for systemic absorption. However, development problems occur for drugs with poor water solubility and/or gastrointestinal permeability. It is generally believed that the in-vivo bioavailability of poorly water-soluble drugs from Class II of the Biopharmaceutics Classification System can be improved by increasing the dissolution rate. We have attempted to increase the in-vivo oral bioavailability of a model Class II drug (griseofulvin) by preparing rapidly-dissolving particles. The solvent-diffusion method was used to prepare particles with hydrophilic surfactants (Brij 76/Tween 80 surfactant blend) and in-vivo studies were conducted in rats. The griseofulvin particles produced were bipyramidal in habit with a particle size of 2.18 +/- 0.12 microm; they contained crystalline drug and a relatively large proportion (12% w/w) of hydrophilic surfactant. The latter and the small particle size ensured rapid particle dispersion and dissolution in-vitro. Thus, within 30 min of the in-vitro dissolution test, the bipyramidal particles had released approximately 70% of drug compared with approximately 10% from the starting material (particle size 12.61 +/- 1.11 microm). However, the rapid and increased drug dissolution in-vitro was not translated to rapid and enhanced absorption in-vivo, and the oral bioavailability of the model drug was found to be the same from the control and from the bipyramidal particles. The poor in-vivo performance of the bipyramidal particles showed that although the dissolution rate of a Class II drug is thought to be a good indicator of its in-vivo bioavailability, this is not always the case.

Administration, Oral↗

Cervical length at 18-22 weeks of gestation for prediction of spontaneous preterm delivery in Hong Kong Chinese women.

OBJECTIVE: To assess the value of a single cervical length measurement by transvaginal sonography (TVS) at the time of mid-trimester anomaly scan for predicting spontaneous preterm delivery (SPD) among Chinese women. METHODS: A prospective observational study was carried out involving 2880 subjects with singleton pregnancies and confirmed gestational age. Cervical length was measured at 18-22 weeks of gestation. RESULTS: The incidence of SPD < 34 weeks and < 37 weeks were 0.7% and 3.7%, respectively. Women with SPD < 34 weeks and SPD < 37 weeks had shorter median cervical lengths (32.6 mm and 36.2 mm, respectively) than those with term deliveries (37.6 mm) (P = 0.006 and 0.025, respectively). The predictive performance of cervical length was better for SPD < 34 weeks compared with < 37 weeks. A cervical length < or = 27 mm, which corresponded to the 4th centile, occurred in 36.8%, 62.5% and 100% of those with SPD < 34, < 30 and < 26 weeks, respectively. The positive likelihood ratio (LR) of a cervical length < or = 27 mm in predicting SPD < 34 weeks was 9.8. Using logistic regression, both short cervix and funneling were independent predictors for SPD < 34 weeks of gestation. The coexistence of funneling and a cervical length < or = 27 mm gave a positive predictive value (PPV) and LR of SPD < 34 weeks of 14.7% and 26.0, respectively. CONCLUSIONS: Mid-trimester cervical length is predictive of SPD in Chinese women. However, given the low PPV of a short cervical length, its clinical utility is still limited in low-risk populations.

Adult↗

Single vs. two steroid injections for carpal tunnel syndrome: a randomised clinical trial.

We investigated the efficacy of a single vs. double steroid injections in the treatment of carpal tunnel syndrome (CTS) in a randomised double-blind controlled trial. Patients with idiopathic CTS were randomised into (i) one group receiving a baseline methylprednisolone acetate injection plus a saline injection 8 weeks later and (ii) a second group receiving methylprednisolone acetate injection at baseline and at 8 weeks. The primary outcome was the Global Symptom Score (GSS). Forty patients were recruited. By 40 weeks, the mean GSS improved from 25.6 to 14.1 in the single-injection group whereas from 26.7 to 12.6 in the reinjection group, but there was no significant difference in GSS between the two groups (p = 0.26). There were also no significant differences in terms of electrophysiological and functional outcomes. The results suggest that an additional steroid injection confers no added benefit to a single injection in terms of symptom relief.

Analgesia↗

Successful treatment of surgically induced necrotizing scleritis with tacrolimus.

A 46-year-old man developed surgically induced necrotizing scleritis (SINS) 7 months following uneventful primary bare sclera pterygium excision. The patient underwent two scleral patch grafts for SINS but despite the use of cyclophosphamide and azathioprine, the scleral patch grafts failed within 1 month of surgery on both occasions. Tacrolimus was used for his third scleral patch graft. No recurrence of necrotizing scleritis was observed for 2 years. Tacrolimus may be considered as a valuable adjunctive immunosuppressant in the management of resistant necrotizing scleritis.

Graft Survival↗

Determination of complete nucleotide sequence of Hibiscus latent Singapore virus: evidence for the presence of an internal poly(A) tract.

We have sequenced the complete genome of a hibiscus-infecting tobamovirus, Hibiscus latent Singapore virus (HLSV). The experimental host range of HLSV is similar to that of another distinct species of hibiscus infecting tobamovirus, Hibiscus latent Fort Pierce virus (HLFPV). The genomic structure of HLSV is similar to other tobamoviruses in general. It consists of a 5' untranslated region (UTR), followed by ORFs encoding for a 128 kDa protein and a 186 kDa readthrough protein, a 30 kDa movement protein (MP), 18 kDa coat protein (CP) and a 3' UTR. The unique feature of HLSV is the presence of a poly(A) tract within its 3' UTR. In our previous work, we have reported MP and CP sequences of HLSV and its phylogenetic analysis. Here we report the complete nucleotide sequence of HLSV, phylogenetic analysis of the nucleotide and amino acid sequences of 128/186 kDa ORFs and the presence of a uniquely located poly(A) tract within the 3' UTR.

3' Untranslated Regions↗

Long-term outcome of carpal tunnel syndrome after conservative treatment.

The purpose of this study was to investigate the long-term prognosis of patients with carpal tunnel syndrome (CTS). We prospectively followed-up patients with CTS for 80 weeks. Thirty cases had been treated with a single injection of methylprednisolone acetate and another 30 with a 10-day course of prednisolone. At the end of the follow-up period, there were no significant differences in symptoms as measured by global symptom score and in the proportion of patients who progressed to decompressive surgery. Few patients who were not operated on (11.4%) remain asymptomatic.

Administration, Oral↗

Breakage of resistance to Cucumber mosaic virus by co-infection with Zucchini yellow mosaic virus: enhancement of CMV accumulation independent of symptom expression.

Resistance to the cucumovirus Cucumber mosaic virus (CMV) in cucumber cv. Delila was manifested as a very low level of accumulation of viral RNA and capsid protein, and an absence of CMV-induced symptoms. In addition, resistance was observed at the single cell level, with a reduction in accumulation of CMV RNAs, compared to accumulation in cells of the susceptible cucumber cv. Bet Alpha. Resistance to CMV in cv. Delila was broken by co-infection with the potyvirus Zucchini yellow mosaic virus (ZYMV). Resistance breakage in cv. Delila plants was manifested by an increase in the accumulation of (+) and (-) CMV RNA as well as CMV capsid protein, with no increase in the level of accumulation of ZYMV. Resistance breakage in the resistant cultivar by ZYMV also occurred at the single cell level. Thus, synergistic interactions known to occur between a potyvirus and a cucumovirus led to resistance breakage during a double infection. However, resistance breakage was not accompanied by an increase in disease symptoms beyond those induced by ZYMV itself. On co-inoculation with an asymptomatic variant of ZYMV-AG an enhancement of CMV infection occurred without disease manifestation. Consequently, intensification of viral RNA and capsid protein accumulation can occur without a corresponding increase in disease development, suggesting that different host genes regulate viral accumulation and disease development in the CMV-resistant cucumber plants.

Capsid Proteins↗

An unusual cause of carpal tunnel syndrome.

Tuberculosis is an uncommon cause of carpal tunnel syndrome. We report a patient with systemic lupus erythematosus who developed hand numbness. Ultrasonic, operative and microbiological findings supported the diagnosis of median nerve compression secondary to a tuberculous abscess. The symptoms resolved with surgical excision and antituberculous chemotherapy.

Adult↗

Discriminatory sonographic criteria for the diagnosis of carpal tunnel syndrome.

OBJECTIVE: Sonographic examination of the median nerve has been suggested as a useful alternative to electrophysiologic study in the diagnosis of carpal tunnel syndrome. To determine its usefulness and the best diagnostic criterion, sonograms of patients with the disease were compared with sonograms of healthy subjects in a case-control study. METHODS: Patients with carpal tunnel syndrome and asymptomatic controls who were matched for age and sex were enrolled and underwent sonography of the wrists. Eight separate sonographic criteria were analyzed in each wrist. Data from the patient group and the control group were compared to establish optimal diagnostic criteria for carpal tunnel syndrome, using receiver operating characteristic analytic techniques. RESULTS: Thirty-five patients with carpal tunnel syndrome and 35 asymptomatic controls were examined. Increased cross-sectional area of the median nerve was found to be the most predictive measure of carpal tunnel syndrome, proximal to the tunnel inlet, at the tunnel inlet, and at the tunnel outlet, with significant differences between patients and controls. Using a receiver operating characteristic curve, a cut-off value >0.098 cm(2) at the tunnel inlet provided a diagnostic sensitivity of 89% and a specificity of 83%. CONCLUSION: Sonographic measurement of the median nerve cross-sectional area is both sensitive and specific for the diagnosis of carpal tunnel syndrome.

Adult↗

Hibiscus virus S is a new subgroup II tobamovirus: evidence from its unique coat protein and movement protein sequences.

The coat protein (CP) and movement protein (MP) sequences of a new tobamovirus infecting Hibiscus rosa-sinensis L were determined. The CP gene encodes 163 amino acid (aa) residues and with a theoretical molecular weight of 18.19 kDa. The MP gene encodes 282 amino acids and its theoretical molecular weight is 30.36 kDa. The nucleotide (nt) and aa sequences of the CP were 46.88 % to 51.63 % and 45.34 % to 57.06 % identical to other tobamoviruses, respectively. The nt and aa sequence identities of MP ranged from 38.81 % to 43.90 % and 30.85 % to 37.88 %, respectively. The predicted virion origin of assembly (OAS) was located in the CP gene. Phylogenetic trees generated based on the nt and aa sequences of both CP and MP genes indicate that this new virus clusters with members of subgroup II of tobamoviruses. Although this hibiscus virus shared a high nt and aa sequence identity with Sunn-hemp mosaic virus (SHMV), Western analysis showed that it is serologically unrelated to SHMV. We propose the name Hibiscus virus S (HVS) for this Singapore isolate. This is the first report on partial nt sequence of a tobamovirus that infects hibiscus.

Blotting, Northern↗