Skin whitening capability of shikimic acid pathway compound.

OBJECTIVE: To examine the skin whitening capabilities of shikimic acid pathway compounds and find the most effective molecule to be used as the active ingredient for skin whitening products. MATERIALS AND METHODS: Skin whitening is the practice of using chemical substances to lighten skin tone by the lessening the concentration of melanin. The whitening efficacy of shikimic acid pathway compounds was evaluated. Eight compounds in the shikimic acid pathway were chosen for this study: benzoic acid, p-coumaric acid, vanillic acid, syringic acid, quinic acid, shikimic acid, orcinol monohydrate, and phenyl pyruvic acid. We measured the tyrosinase inhibitory capacity of the compounds in the animal model of zebrafish and also evaluated the compounds' anti-oxidant activities using the DPPH radical scavenging, and ABTS+ free radical scavenging tests. Compounds' cytotoxicity effects were also evaluated. RESULTS: Amongst eight shikimic acid pathway compounds used in this study, shikimic acid was the most potent tyrosinase-inhibitor and the most efficient compound to be used as an active ingredient for skin whitening. Shikimic acid revealed a good radical scavenging activity (RAS) with low cell toxicity. CONCLUSIONS: Promising results obtained in this study may open a new window of opportunity to introduce another compound to be used in the skin-whiting cosmetics industry.

Use of biologics for inflammatory bowel disease in Hong Kong: consensus statement.

UNLABELLED: OBJECTIVE; With the increasing use of biologics in patients with inflammatory bowel disease, the Hong Kong IBD Society developed a set of consensus statements intended to serve as local recommendations for clinicians about the appropriate use of biologics for treating inflammatory bowel disease. PARTICIPANTS: The consensus meeting was held on 9 July 2011 in Hong Kong. Draft consensus statements were developed by core members of the Hong Kong IBD Society, including local gastroenterologists and colorectal surgeons experienced in managing patients with inflammatory bowel disease. EVIDENCE: Published literature and conference proceedings on the use of biologics in management of inflammatory bowel disease, and guidelines and consensus issued by different international and regional societies on recommendations for biologics in inflammatory bowel disease patients were reviewed. CONSENSUS PROCESS: Four core members of the consensus group drafted 19 consensus statements through the modified Delphi process. The statements were first circulated among a clinical expert panel of 15 members for review and comments, and were finalised at the consensus meeting through a voting session. A consensus statement was accepted if at least 80% of the participants voted "accepted completely or "accepted with some reservation". CONCLUSIONS: Nineteen consensus statements about inflammatory bowel disease were generated by the clinical expert panel meeting. The statements were divided into four parts which covered: (1) epidemiology of the disease in Hong Kong; (2) treatment of the disease with biologics; (3) screening and contra-indications pertaining to biologics; and (4) patient monitoring after use of biologics. The current statements are the first to describe the appropriate use of biologics in the management of inflammatory bowel disease in Hong Kong, with an aim to provide guidance for local clinical practice.

Hong Kong experiences the 'Ultimate superbug': NDM-1 Enterobacteriaceae.

We report the second imported case of New Delhi metallo-beta-lactamase (NDM-1) Enterobacteriaceae encountered in Hong Kong soon after the patient's arrival in the territory for medical care. As NDM-1 is spreading throughout the world via international travel, being an international city, Hong Kong was always expected to encounter the same public health threat. This case also illustrates the importance of active surveillance of at-risk patients in preventing the spread of this 'superbug'.

Evaluation of in-house and commercial genotyping assays for molecular typing of hepatitis C virus in Hong Kong.

This study aims to evaluate genotyping assays for hepatitis C virus (HCV). An in-house nucleic acid sequencing method is performed in parallel with the Roche Linear Array HCV genotyping test on 73 HCV-positive (66 clinical samples and seven proficiency testing quality control samples) and 12 HCV-negative samples (11 clinical samples and one proficiency testing sample). The performance of the in-house method was comparable with that of the Roche assay (concordance rate: 89.4%). Discordant results included four mixed infections missed by the in-house method, two false-negatives with the Roche assay, and three discrepant results. The in-house method exhibited a higher resolution (subtype vs. genotype level) at a lower running cost (25% of the commercial assay). The in-house method was also used to genotype 375 HCV clinical isolates to determine the genotypic distribution of HCV in Hong Kong between 2005 and 2008. A total of 441 (52.8%) clinical isolates proved to be genotype 1, which shows a poorer response to interferon therapy. Genotype 6 was the next most common (32.0%). Prevalence of genotypes 2 and 3 was 7.7% and 6.6%, respectively, and prevalence of genotypes 4 and 5 was 0.9% and 0%, respectively. Although the in-house nucleic acid sequencing method failed to detect a few cases of mixed HCV infection, its high resolution and low running cost make it suitable for surveillance and outbreak investigation.

Analytical sensitivity of rapid influenza antigen detection tests for swine-origin influenza virus (H1N1).

BACKGROUND: A novel swine origin influenza virus (S-OIV) (H1N1) is spreading worldwide and threatens to become pandemic. OBJECTIVES: Determine analytical sensitivity of selected commercially available rapid influenza antigen detection tests in detecting S-OIV H1N1. STUDY DESIGN: Serial dilutions of two S-OIV isolates, one seasonal influenza A (H1N1) isolate and a nasopharyngeal aspirate from a patient with S-OIV disease were tested in five commercially available influenza antigen detection tests and by virus isolation in cell culture. Viral M gene copy number was determined by quantitative PCR methods. RESULTS: The analytical sensitivity of the five influenza antigen detection tests for S-OIV (tissue culture infectious dose 50 (TCID(50)) log(10)3.3-4.7 was comparable with that of seasonal influenza (TCID(50) log(10)4.0-4.5). CONCLUSION: The analytical sensitivity of the selected influenza A antigen detection tests for detection of S-IOV was comparable with that of seasonal influenza H1N1.

Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic susceptibility to SARS and other infections.

1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.

Interpositional arthroplasty using autogenous costal cartilage graft for temporomandibular joint ankylosis in adults.

This retrospective study evaluated 11 adult patients with TMJ ankylosis treated by interpositional arthroplasty using autogenous costal cartilage grafts between 1985 and 2003. Minimum follow-up was 2 years. Basic personal data, function of TMJ and complications of operation were recorded. Mouth opening increased during operation by a mean of 25.5mm and postoperatively by a mean of 26.2mm. The procedure failed in one case with recurrent ankylosis. The remaining 10 cases had final opening ranges in excess of 30mm. Complications included one numb lower lip. There were no instances of a facial nerve or internal maxillary artery injury. Consideration is given to the width and level of gap arthroplasty, fixation of the grafts, complications at both donor and recipient sites, postoperative physical therapy, occlusal change, and the need for coronoidectomy. This study demonstrated that autogenous costal cartilage is a suitable material for interpositional arthroplasty in adults. Complications were low. The intraoral approach and the role of postoperative physical therapy appear key elements in the success of this procedure.

Disease progression in Chinese chronic hepatitis C patients with persistently normal alanine aminotransaminase levels.

BACKGROUND: Although chronic hepatitis C virus-infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression. AIM: To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time. METHODS: Eighty-two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow-up was 8.1 years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. RESULTS: At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03-2.5, P = 0.02). CONCLUSION: Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.

48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection.

BACKGROUND/AIM: Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown. METHOD: We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated interferon alpha-2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL at week 72. RESULTS: Twenty-nine patients were treated with 48 weeks of pegylated-interferon-alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated-interferon-alpha-2a was independently associated with sustained virological response (P = 0.04 adjusted hazards-ratio 9.37). CONCLUSION: Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B.

Clopidogrel-induced hepatotoxicity after percutaneous coronary stenting.

Clopidogrel, an adenosine diphosphate receptor blocker, is widely used as an adjunctive antiplatelet therapy in acute coronary syndrome and percutaneous coronary stenting. The occurrence of hepatotoxicity is rare. We describe the occurrence of symptomatic liver disease in a 74-year-old man 5 weeks following commencement of therapy with clopidogrel. The reported cases of clopidogrel-induced hepatotoxicity are reviewed and the clinical significance of this event are discussed.

Treatment of severe acute respiratory syndrome.

The best treatment strategy for severe acute respiratory syndrome (SARS) is still unknown. Ribavirin and corticosteroids were used extensively during the SARS outbreak. Ribavirin has been criticized for its lack of efficacy. Corticosteroids are effective in lowering the fever and reversing changes in the chest radiograph but have the caveat of encouraging viral replication. The effectiveness of corticosteroids has only been suggested by uncontrolled observations, and the role of these agents in therapy remains to be established by randomized controlled studies. Both ribavirin and corticosteroids have very significant side effects. The lopinavir/ritonavir combination has been shown to reduce the intubation rate and the incidence of adverse clinical outcomes when used with ribavirin. When patients deteriorate clinically despite treatment with ribavirin and corticosteroids, rescue treatment with convalescent plasma and immunoglobulin may be beneficial. Noninvasive positive pressure ventilation is a sound treatment for SARS patients with respiratory failure if administered with due precaution in the correct environment. Interferons and other novel agents may hold promise as useful anti-SARS therapies in the future. The experience with traditional Chinese medicine is encouraging, and its use as an adjuvant should be further investigated.

Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study.

BACKGROUND: It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. METHOD: One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. RESULTS: There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. CONCLUSION: The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.

Prevention of transfusion-transmitted hepatitis E by donor-initiated self exclusion.

Safety in blood transfusion has all along been focused on blood borne viruses like HIV, hepatitis B and C. However, infective agents that are not usually transmitted through blood may also pose risk to transfusion if the donor gives blood in the early-viraemic phase. A case report of potential transfusion-transmitted hepatitis E (HEV) is described. It shows the virus can be transmissible via blood because of the presence of HEV RNA in the blood donated. Pre-donation health screening was unable to exclude this asymptomatic donor. But donor-initiated call back system which acts as an additional safety net prevented the release of the potential infective blood products.

The Quantitative Assessment of Gd-DTPA in Contrast Enhanced Magnetic Resonance Angiography.

Recently, the use of MRI contrast agents has been proven to be substantially improved sensitivity and specificity in many clinical applications. CE-MRA has higher blood signal based on the T1 and T2-shortening property of contrast agents, so that even the small vessels can be visualized. The use of contrast agents can improve lesion detection and characterization. The routinely used dose of contrast agents in the routine MRI examinations only relies on the weight of the subject. The purpose of this study is to obtain the clinically optimal dose for 3D-TOF (time-of-flight) pulse sequences for CE-MRA examinations. In the phantom study, ten test tubes were filled with saline mixed with different dose of Gd-DTPA. It is found that the optimal dose of Gd-DTPA for saline phantom by using 3D-TOF pulse sequences is 20 mM. Also, there has no differences of optimal doses between Omniscan and Magnivist contrast agents Gd-DTPA. The results show that consistent high quality CE-MRA images might be obtained by using 0.25M Gd-DTPA (half of the routine dose) with 3~4 cc/sec injection rate for all clinical cases. The benefits of this study might be to minimize dose and potential toxicity. Additionally, the decrease of the cost of contrast agents might be achieved. It is expected to provide the recommended dose of Gd-DTPA for contrast enhanced MRA in clinical routine diagnosis.

Re-emergence of fatal human influenza A subtype H5N1 disease.

Human disease associated with influenza A subtype H5N1 re-emerged in January, 2003, for the first time since an outbreak in Hong Kong in 1997. Patients with H5N1 disease had unusually high serum concentrations of chemokines (eg, interferon induced protein-10 [IP-10] and monokine induced by interferon gamma [MIG]). Taken together with a previous report that H5N1 influenza viruses induce large amounts of proinflammatory cytokines from macrophage cultures in vitro, our findings suggest that cytokine dysfunction contributes to the pathogenesis of H5N1 disease. Development of vaccines against influenza A (H5N1) virus should be made a priority.

Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study.

OBJECTIVES: To investigate the possible benefits and adverse effects of the addition of lopinavir/ritonavir to a standard treatment protocol for the treatment of severe acute respiratory syndrome. DESIGN: Retrospective matched cohort study. SETTING: Four acute regional hospitals in Hong Kong. PATIENTS AND METHODS: Seventy-five patients with severe acute respiratory syndrome treated with lopinavir/ritonavir in addition to a standard treatment protocol adopted by the Hospital Authority were matched with controls retrieved from the Hospital Authority severe acute respiratory syndrome central database. Matching was done with respect to age, sex, the presence of co-morbidities, lactate dehydrogenase level and the use of pulse steroid therapy. The 75 patients treated with lopinavir/ritonavir were divided into two subgroups for analysis: lopinavir/ritonavir as initial treatment, and lopinavir/ritonavir as rescue therapy. These groups were compared with matched cohorts of 634 and 343 patients, respectively. Outcomes including overall death rate, oxygen desaturation, intubation rate, and use of pulse methylprednisolone were reviewed. RESULTS: The addition of lopinavir/ritonavir as initial treatment was associated with a reduction in the overall death rate (2.3%) and intubation rate (0%), when compared with a matched cohort who received standard treatment (15.6% and 11.0% respectively, P<0.05) and a lower rate of use of methylprednisolone at a lower mean dose. The subgroup who had received lopinavir/ritonavir as rescue therapy, showed no difference in overall death rate and rates of oxygen desaturation and intubation compared with the matched cohort, and received a higher mean dose of methylprednisolone. CONCLUSION: The addition of lopinavir/ritonavir to a standard treatment protocol as an initial treatment for severe acute respiratory syndrome appeared to be associated with improved clinical outcome. A randomised double-blind placebo-controlled trial is recommended during future epidemics to further evaluate this treatment.

Coronavirus as a possible cause of severe acute respiratory syndrome.

BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. METHODS: We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. FINDINGS: Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. INTERPRETATION: A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.