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1.
QJM ; 117(2): 125-132, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-37824396

ABSTRACT

BACKGROUND: It is unclear how the coronavirus disease 2019 (Covid-19) pandemic has affected multimorbidity incidence among those with one pre-existing chronic condition, as well as how vaccination could modify this association. AIM: To examine the association of Covid-19 infection with multimorbidity incidence among people with one pre-existing chronic condition, including those with prior vaccination. DESIGN: Nested case-control study. METHODS: We conducted a territory-wide nested case-control study with incidence density sampling using Hong Kong electronic health records from public healthcare facilities and mandatory Covid-19 reports. People with one listed chronic condition (based on a list of 30) who developed multimorbidity during 1 January 2020-15 November 2022 were selected as case participants and randomly matched with up to 10 people of the same age, sex and with the same first chronic condition without having developed multimorbidity at that point. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of multimorbidity. RESULTS: In total, 127 744 case participants were matched with 1 230 636 control participants. Adjusted analysis showed that there were 28%-increased odds of multimorbidity following Covid-19 [confidence interval (CI) 22% to 36%] but only 3% (non-significant) with prior full vaccination with BNT162b2 or CoronaVac (95% CI -2% to 7%). Similar associations were observed in men, women, older people aged 65 or more, and people aged 64 or younger. CONCLUSIONS: We found a significantly elevated risk of multimorbidity following a Covid-19 episode among people with one pre-existing chronic condition. Full vaccination significantly reduced this risk increase.


Subject(s)
COVID-19 , Male , Humans , Female , Aged , COVID-19/epidemiology , COVID-19/prevention & control , Multimorbidity , Case-Control Studies , BNT162 Vaccine , Chronic Disease
2.
Hong Kong Med J ; 29(3): 224-232, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37303104

ABSTRACT

INTRODUCTION: The number of poisoning cases involving attention deficit hyperactivity disorder (ADHD) medications has reportedly risen with their increased use. However, there is limited relevant evidence from Asia. We analysed the characteristics of poisoning events involving these medications in Hong Kong. METHODS: We retrieved data regarding ADHD medication-related poisoning cases from the Hong Kong Poison Information Centre and conducted a descriptive analysis of the demographic information and poisoning information including sources of cases, exposure reason, exposure location, and outcome. The HKPIC data were linked with the Hospital Authority Clinical Data Analysis and Reporting System (CDARS) via de-identified Accident and Emergency numbers of public hospitals to investigate clinical characteristics. We also retrieved ADHD medication prescription records from the CDARS, then compared trends between poisoning cases and ADHD medication use. RESULTS: We identified 72 poisoning cases involving ADHD medications between 2009 and 2019, of which approximately 70% occurred in the affected individual's residence; most were intentional poisoning events (65.3%). No statistically significant association was observed between ADHD medication prescription trends and poisoning events involving ADHD medications. Of the 66 cases (91.7%) successfully linked to CDARS, 40 (60.6%) occurred in individuals with ADHD (median age: 14 years); 26 (39.4%) occurred in individuals who lacked ADHD (median age: 33 years) but displayed higher rates of other mental disorders including depression and anxiety. CONCLUSION: No significant correlation was evident between ADHD medication prescriptions and poisoning events involving ADHD medications. However, medication management and caregiver education must be emphasised to prevent potential poisoning events.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Humans , Adolescent , Adult , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/epidemiology , Central Nervous System Stimulants/therapeutic use , Hong Kong/epidemiology , Anxiety Disorders/drug therapy
3.
Int J Biol Macromol ; 237: 123982, 2023 May 15.
Article in English | MEDLINE | ID: mdl-36907297

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged since the early 1960s. The increasing resistance of pathogens to currently used antibiotics requires the urgent discovery of new antimicrobials effective in combating drug-resistant bacteria. From past to present, medicinal plants are useful to cure human diseases. Corilagin (ß-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), commonly found in Phyllanthus species, exerts potentiating effect on ß-lactams against MRSA. However, its biological effect may not be fully utilized. Therefore, incorporating microencapsulation technology with the delivery of corilagin would be more effective in utilizing the potential effect on biomedical applications. This work reports the development of a safe micro-particulate system which combined agar with gelatin as wall matrix materials for topical delivery of corilagin in order to eliminate the potential toxicity of the crosslinker formaldehyde. The optimal parameters for microsphere preparation were identified and the particle size of optimal microspheres was 20.11 µm ± 3.58. Antibacterial studies revealed that micro-trapped corilagin (minimum bactericidal concentration, MBC = 0.5 mg/mL) possessed a higher potency against MRSA than free corilagin (MBC = 1 mg/mL). The in vitro skin cytotoxicity showed the safety of the corilagin-loaded microspheres for topical applications, with approximately 90 % of HaCaT cell viability. Our results demonstrated the potential of corilagin-loaded gelatin/agar microspheres for the applicable bio-textile products to treat drug-resistant bacterial infections.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Humans , Staphylococcus aureus , Gelatin/pharmacology , Agar/pharmacology , Microspheres , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology
4.
J Prev Alzheimers Dis ; 9(4): 715-724, 2022.
Article in English | MEDLINE | ID: mdl-36281676

ABSTRACT

BACKGROUND: Hypertension is a recognized risk factor for dementia. However, evidence for using antihypertensive agents to reduce the risk of Alzheimer's disease in people with hypertension is inconclusive. OBJECTIVE: To examine the association between antihypertensive agents and the incidence of Alzheimer's disease in adults with hypertension and normal cognition. DESIGN: We conducted a systemic review and performed meta-analyses using Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Web of science and Scopus, from inception to 18th February 2022. SETTING: Cohort and case-control studies. PARTICIPANTS: Adults ≥ 40 years with hypertension and normal cognition. INTERVENTION: Antihypertensive agents. MEASUREMENTS: We performed two separate meta-analyses, pooling the adjusted relative risk (RR) of non-antihypertensive comparator and antihypertensive comparator study design. RESULTS: We included nine studies, totalling 1,527,410 individuals. Meta-analysis of non-antihypertensive user comparator studies found that the use of antihypertensive agents is associated with a reduced risk of incident Alzheimer's disease (RR= 0.94, 95% CI 0.90-0.99; p=0.01). Meta-analysis of antihypertensive comparator studies found evidence that angiotensin II receptor blocker users are associated with a reduction in the risk of Alzheimer's disease compared to other antihypertensive agents (RR= 0.78, 95% CI 0.68-0.88; p< 0.001). CONCLUSION: Our review provides evidence that the use of antihypertensive agents is associated with a lower incidence of Alzheimer's disease. The use of angiotensin II receptor blockers may provide the most benefit among antihypertensive agents. Lowering raised blood pressure may not be the only mechanism for cognitive protection and further investigation of the effects of angiotensin II on cognition is indicated.


Subject(s)
Alzheimer Disease , Hypertension , Humans , Antihypertensive Agents/therapeutic use , Alzheimer Disease/epidemiology , Alzheimer Disease/prevention & control , Alzheimer Disease/complications , Angiotensin II , Hypertension/complications , Hypertension/drug therapy , Hypertension/prevention & control , Angiotensin Receptor Antagonists/therapeutic use
5.
Drug Chem Toxicol ; 45(2): 834-838, 2022 Mar.
Article in English | MEDLINE | ID: mdl-32538189

ABSTRACT

There are an estimated 1 billion cases of superficial fungal infection globally. Fungal pathogens form biofilms within wounds and delay the wound healing process. Miconazole and terbinafine are commonly used to treat fungal infections. They induce the accumulation of reactive oxygen species (ROS) in fungi, resulting in the death of fungal cells. ROS are highly reactive molecules, such as oxygen (O2), superoxide anion (O2•-), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). Although ROS generation is useful for killing pathogenic fungi, it is cytotoxic to human keratinocytes. To the best of our knowledge, the effect of miconazole and terbinafine on HaCaT cells has not been studied with respect to intracellular ROS stimulation. We hypothesized that miconazole and terbinafine have anti-wound healing effects on skin cells when used in antifungal treatment because they generate ROS in fungal cells. We used sulforhodamine B protein staining to investigate cytotoxicity and 2',7'-dichlorofluorescein diacetate to determine ROS accumulation at the 50% inhibitory concentrations of miconazole and terbinafine in HaCaT cells. Our preliminary results showed that topical treatment with miconazole and terbinafine induced cytotoxic responses, with miconazole showing higher cytotoxicity than terbinafine. Both the treatments stimulated ROS in keratinocytes, which may induce oxidative stress and cell death. This suggests a negative correlation between intracellular ROS accumulation in keratinocytes treated with miconazole or terbinafine and the healing of fungi-infected skin wounds.


Subject(s)
Hydrogen Peroxide , Miconazole , Humans , Hydrogen Peroxide/pharmacology , Keratinocytes , Miconazole/metabolism , Miconazole/toxicity , Reactive Oxygen Species/metabolism , Terbinafine/metabolism , Terbinafine/toxicity
6.
Clin Drug Investig ; 41(9): 817-823, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34368943

ABSTRACT

BACKGROUND AND OBJECTIVE: Ketamine is an N-methyl-D-aspartate receptor (NMDA) antagonist used widely as an intravenous analgesic for treatment of acute pain. Its use as oral and sublingual analgesics is not well studied. This study aims to compare the clinical efficacy and tolerability of oral (PO) versus sublingual (SL) ketamine lozenges in adult patients with moderate-to-severe breakthrough pain. METHODS: The study had a randomized, double-blind crossover design in 23 inpatients requiring ketamine as rescue analgesics when pain scores exceeded 4/10 on the Numerical Rating Scales. Each participant received either SL 50 mg ketamine lozenge and PO placebo lozenge or SL placebo lozenge and PO 50 mg ketamine lozenge in two treatment periods with a minimum 24-h washout. Pain scores and adverse effects were documented half hourly for the first 2 h, then one hourly for the next 2 h after treatment. The time to first effect and time to meaningful pain relief were recorded. Patients reported their satisfaction and a global impression of change (GIC) at the end of each treatment period. Data were analysed using random effects regression models. RESULTS: Sixteen subjects completed both days, 7 completed 1 day. Time to first effect was 13.1 min PO versus 6.6 min SL (p = 0.069), time to meaningful pain relief was 29.4 min PO versus 10.8 min SL (p = 0.02). Pain scores were not significantly different at all time points post-treatment. Satisfaction and GIC scores were similar for both groups. Overall, adverse events occurred more often with SL administration (p = 0.02). CONCLUSIONS: Sublingual administration of ketamine led to a faster onset of pain relief (but also a higher adverse event rate), but in all other aspects treatment with ketamine given sublingually and orally produced similar analgesic effects. ACTRN: ACTRN12621000240842, 08/03/2021, retrospectively registered.


Subject(s)
Acute Pain , Ketamine , Acute Pain/diagnosis , Acute Pain/drug therapy , Administration, Sublingual , Adult , Analgesics/therapeutic use , Analgesics, Opioid/therapeutic use , Double-Blind Method , Humans , Ketamine/therapeutic use , Pain Management , Treatment Outcome
7.
Emerg Microbes Infect ; 9(1): 2190-2199, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32940572

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Patient Outcome Assessment , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Host-Pathogen Interactions/immunology , Humans , Organ Specificity , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Time Factors
8.
J Orthop Translat ; 24: 58-65, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32695605

ABSTRACT

OBJECTIVE: To analyze the effectiveness of exercise interventions on falls and fall-related fracture prevention among community-dwelling elderlies. METHODS: Literature search was conducted in Pubmed and Embase. Keywords used for literature search were "fracture" AND "fall" AND "exercise". Randomized controlled trials involving community-dwelling elderlies older than 60 years old with physical exercises as intervention were included. A systematic review and meta-analysis was performed. The primary outcomes were falls and fractures. RESULTS: Twelve studies were included and 4784 participants were involved with a mean age of 75.4. The most common exercise interventions were strength and balance exercises. The results of meta-analysis of 11 studies showed that exercise intervention had beneficial effect on fall prevention (RR = 0.71, 95% CI, 0.62-0.82; I2 = 24%, p < 0.0001). The effect was better when exercise intervention applied to women participants (RR = 0.64, 95% CI, 0.49-0.83; I2 = 28%, p = 0.00009) compared to men and women participants (RR = 0.75, 95% CI, 0.64-0.89; I2 = 24%, p = 0.001). The results of meta-analysis of seven studies showed that physical exercise had significant effect on fracture prevention (RR = 0.54, 95% CI, 0.35-0.83; I2 = 25%, p = 0.005). However, the effect was significant when exercise intervention applied to women participants only (RR = 0.37, 95% CI, 0.20-0.67; I2 = 0%, p = 0.001) but not significant when exercise intervention applied to both genders (RR = 0.80, 95% CI, 0.58-1.09; I2 = 0%, p = 0.15). CONCLUSION: Exercise interventions, especially the combination of strength and balance training, were effective in preventing falls. Resistance exercises and jumping exercises were effective for fracture prevention among community-dwelling older population. The effectiveness of exercise interventions on fracture prevention have more significant effect on women. Further studies are needed to test the effectiveness of exercise interventions in men. TRANSLATIONAL POTENTIAL: The use of effective exercises or biophysical interventions including vibration therapy can be incorporated into Fracture Liaison Services to prevent future fall and fracture.

9.
Chem Biol Interact ; 320: 109023, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-32097615

ABSTRACT

Antimicrobial resistance remains a serious problem that results in high mortality and increased healthcare costs globally. One of the major issues is that resistant pathogens decrease the efficacy of conventional antimicrobials. Accordingly, development of novel antimicrobial agents and therapeutic strategies is urgently needed to overcome the challenge of antimicrobial resistance. A potential strategy is to kill pathogenic microorganisms via the formation of reactive oxygen species (ROS). ROS are defined as a number of highly reactive molecules that comprise molecular oxygen (O2), superoxide anion (O2•-), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). ROS exhibit antimicrobial actions against a broad range of pathogens through the induction of oxidative stress, which is an imbalance between ROS and the ability of the antioxidant defence system to detoxify ROS. ROS-dependent oxidative stress can damage cellular macromolecules, including DNA, lipids and proteins. This article reviews the antimicrobial action of ROS, challenges to ROS hypothesis, work to solidify ROS-mediated antimicrobial lethality hypothesis, recent developments in antimicrobial agents using ROS as an antimicrobial strategy, safety concerns related to ROS, and future directions in ROS research.


Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , DNA, Bacterial/drug effects , Reactive Oxygen Species/metabolism , Animals , Humans , Oxidative Stress
10.
Crit Rev Microbiol ; 44(1): 40-78, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28423970

ABSTRACT

Antimicrobial resistance of disease-related microorganisms is considered a worldwide prevalent and serious issue which increases the failure of treatment outcomes and leads to high mortality. Considering that the increased resistance to systemic antimicrobial therapy often needs of the use of more toxic agents, topical antimicrobial therapy emerges as an attractive route for the treatment of infectious diseases. The topical antimicrobial therapy is based on the absorption of high drug doses in a readily accessible skin surface, resulting in a reduction of microbial proliferation at infected skin sites. Topical antimicrobials retain the following features: (a) they are able to escape the enzymatic degradation and rapid clearance in the gastrointestinal tract or the first-pass metabolism during oral administration; (b) alleviate the physical discomfort related to intravenous injection; (c) reduce possible adverse effects and drug interactions of systemic administrations; (d) increase patient compliance and convenience; and (e) reduce the treatment costs. Novel antimicrobials for topical application have been widely exploited to control the emergence of drug-resistant microorganisms. This review provides a description of antimicrobial resistance, common microorganisms causing skin and soft tissue infections, topical delivery route of antimicrobials, safety concerns of topical antimicrobials, recent advances, challenges and future prospective in topical antimicrobial development.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Skin Diseases, Bacterial/drug therapy , Soft Tissue Infections/drug therapy , Administration, Topical , Bacteria/drug effects , Bacteria/genetics , Bacteria/metabolism , Drug Resistance, Bacterial , Humans , Skin Diseases, Bacterial/microbiology , Soft Tissue Infections/microbiology
11.
Eur J Med Chem ; 124: 537-543, 2016 Nov 29.
Article in English | MEDLINE | ID: mdl-27598239

ABSTRACT

Two complexes dichloro(9,9-dihexyl-4,5-diazafluorene)platinum(II) (Pt-DHF) and dichloro(9,9-dihexyl-4,5-diazafluorene)palladium(II) (Pd-DHF) were synthesized and their in vivo antitumour activity was investigated using an athymic nude mice model xenografted with human Hep3B carcinoma cells. Pt-DHF- and Pd-DHF-treated groups showed significant tumour growth inhibition (with about 9-fold and 3-fold tumour growth retardation) when compared with the vehicle control group. The liver toxicology effects on the animals of the two compounds were investigated. Pt-DHF and Pd-DHF-treated groups had a lower alanine transaminase and aspartate transaminase values than those of the vehicle treated group as the animals from the vehicle control group had very heavy hepatoma burden. We assume that both complexes could be further investigated as effective antitumour agents and it is worthwhile to study their underlying working mechanism.


Subject(s)
Coordination Complexes/chemical synthesis , Organoplatinum Compounds/chemical synthesis , Organoplatinum Compounds/pharmacology , Palladium/chemistry , Platinum/chemistry , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Disease Models, Animal , Enzyme Activation/drug effects , Heterografts , Humans , Liver/drug effects , Liver Neoplasms/drug therapy , Mice , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/therapeutic use , Palladium/pharmacology , Palladium/therapeutic use , Platinum/pharmacology , Platinum/therapeutic use
12.
Child Care Health Dev ; 42(5): 750-8, 2016 09.
Article in English | MEDLINE | ID: mdl-27349854

ABSTRACT

BACKGROUND: Migrant children refer to rural children who accompany one or both parents to urban area. Empirical evidence showed that compared with their urban counterparts, migrant children had poorer developmental, emotional and psychological health. METHOD: A sample of 1306 migrant children were recruited to examine the characteristics of migrant children and investigate the effects of identity integration, support and socioeconomic factors (e.g. age, gender, type of school, family socioeconomic status, city type) on their subjective wellbeing. RESULTS: Children with higher levels of identity integration, social support, family socioeconomic status, who attended public school and who lived in the third-tiered city of Weihai demonstrated better subjective wellbeing. Social support remained a strong predictor for subjective wellbeing, despite a significant mediating effect of identity integration. CONCLUSIONS: These results highlight the need for policymakers and practitioners alike to address individual factors pertaining to psychological adjustments, as well as social determinants of subjective wellbeing in the context of migration.


Subject(s)
Child Welfare/statistics & numerical data , Social Identification , Social Support , Transients and Migrants/psychology , Adolescent , Child , Child Health , China , Female , Humans , Male , Schools/statistics & numerical data , Social Class , Socioeconomic Factors , Urban Health/statistics & numerical data
13.
Biomed Pharmacother ; 80: 145-150, 2016 May.
Article in English | MEDLINE | ID: mdl-27133051

ABSTRACT

Tumour growth is closely related to the development of new blood vessels to supply oxygen and nutrients to cancer cells. Without the neovascular formation, tumour volumes cannot increase and undergo metastasis. Antiangiogenesis is one of the most promising approaches for antitumour therapy. The exploration of new antiangiogenic agents would be helpful in antitumour therapy. Quinoline is an aromatic nitrogen compound characterized by a double-ring structure which exhibits a benzene ring fused to pyridine at two adjacent carbon atoms. The high stability of quinoline makes it preferable in a variety of therapeutic and pharmaceutical applications, including antitumour treatment. This work is to examine the potential antiangiogenic activity of the synthetic compound 2-Formyl-8-hydroxy-quinolinium chloride. We found that 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of human umbilical vein endothelial cells in vitro. Using the diethylnitrosamine-induced hepatocarcinogenesis model, 2-Formyl-8-hydroxy-quinolinium chloride showed strong antiangiogenic activity. Furthermore, 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of large Hep3B xenografted tumour from the nude mice. We assume that 2-Formyl-8-hydroxy-quinolinium chloride could be a potential antiangiogenic and antitumour agent and it is worthwhile to further study its underlying working mechanism.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Hydroxyquinolines/pharmacology , Quinolinium Compounds/pharmacology , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinogenesis/pathology , Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Cell Death/drug effects , Cell Proliferation/drug effects , Diethylnitrosamine , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Hydroxyquinolines/chemistry , Hydroxyquinolines/therapeutic use , Liver Neoplasms/blood supply , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Mice, Inbred C57BL , Mice, Nude , Quinolinium Compounds/chemistry , Quinolinium Compounds/therapeutic use , Tumor Burden/drug effects , Xenograft Model Antitumor Assays
14.
Springerplus ; 5: 271, 2016.
Article in English | MEDLINE | ID: mdl-27006880

ABSTRACT

BACKGROUND: Candida susceptibility commonly occurs in breast cancer patients. Of which, Candida albicans is considered as a common pathogen causing candidiasis. Martinella iquitosensis (Bignoniaceae) is one of the species belonged to Martinella, distributed widely in Amazon basin. Its root extract yielded two complex substituted tetrahydroquinolines, Martinelline and Martinellic acid which were the first natural non-peptide bradykinin receptor antagonists identified. FINDINGS: In this study, a novel martinelline type analogue, named 2,3,3a,4,5,9b-hexahydro-8-phenoxy-4-(pyridin-2-yl)furo[3,2-c]quinoline, was synthesized and its preliminary anticancer activity and antifungal potential were investigated. This compound showed potential anticancer activity against MDAMB-231 breast cancer cells. Meanwhile it could enhance the fungistatic activity of miconazole against Candida albicans. CONCLUSIONS: These findings provide an implication for the continue investigation and development of martinelline type analogues as therapeutic agents in the future.

15.
J Clin Microbiol ; 53(9): 2942-50, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26135875

ABSTRACT

Persons with hepatitis C virus (HCV) genotype 1a (GT1a) infections harboring a baseline Q80K polymorphism in nonstructural protein 3 (NS3) have a reduced virologic response to simeprevir in combination with pegylated interferon-alfa and ribavirin. We aimed to develop, validate, and freely disseminate an NS3 clinical sequencing assay to detect the Q80K polymorphism and potentially other HCV NS3 drug resistance mutations. HCV RNA was extracted from frozen plasma using a NucliSENS easyMAG automated nucleic acid extractor, amplified by nested reverse transcription-PCR, and sequenced using Sanger and/or next-generation (MiSeq) methods. Sanger chromatograms were analyzed using in-house software (RECall), and nucleotide mixtures were called automatically. MiSeq reads were iteratively mapped to the H77 reference genome, and consensus NS3 sequences were generated with nucleotides present at >20% called as mixtures. The accuracy, precision, and sensitivity for detecting the Q80K polymorphism were assessed in 70 samples previously sequenced by an external laboratory. A comparison of the sequences generated by the Sanger and MiSeq methods with those determined by an external lab revealed >98.5% nucleotide sequence concordance and zero discordant calls of the Q80K polymorphism. The results were both highly repeatable and reproducible (>99.7% nucleotide concordance and 100% Q80K concordance). The limits of detection (>2 and ∼5 log10 IU/ml for the Sanger and MiSeq assays, respectively) are sufficiently low to allow genotyping in nearly all chronically infected treatment-naive persons. No systematic bias in the under- or overamplification of minority variants was observed. Coinfection with other viruses (e.g., HIV and hepatitis B virus [HBV]) did not affect the assay results. The two independent HCV NS3 sequencing assays with the automated analysis procedures described here are useful tools to screen for the Q80K polymorphism and other HCV protease inhibitor drug resistance mutations.


Subject(s)
Antiviral Agents/pharmacology , Genotyping Techniques/methods , Hepatitis C, Chronic/virology , Mass Screening/methods , Mutation, Missense , Simeprevir/pharmacology , Viral Nonstructural Proteins/genetics , Drug Resistance , Hepacivirus/genetics , Hepacivirus/isolation & purification , Humans , Mutant Proteins/genetics , Reproducibility of Results , Sensitivity and Specificity
16.
Int J Mol Med ; 35(2): 503-10, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25482299

ABSTRACT

Aspergillus niger (A. niger) is a common species of Aspergillus molds. Cutaneous aspergillosis usually occurs in skin sites near intravenous injection and approximately 6% of cutaneous aspergillosis cases which do not involve burn or HIV-infected patients are caused by A. niger. Biomaterials and biopharmaceuticals produced from microparticle-based drug delivery systems have received much attention as microencapsulated drugs offer an improvement in therapeutic efficacy due to better human absorption. The frequently used crosslinker, glutaraldehyde, in gelatin-based microencapsulation systems is considered harmful to human beings. In order to tackle the potential risks, agarose has become an alternative polymer to be used with gelatin as wall matrix materials of microcapsules. In the present study, we report the eco-friendly use of an agarose/gelatin-based microencapsulation system to enhance the antifungal activity of gallic acid and reduce its potential cytotoxic effects towards human skin keratinocytes. We used optimal parameter combinations, such as an agarose/gelatin ratio of 1:1, a polymer/oil ratio of 1:60, a surfactant volume of 1% w/w and a stirring speed of 900 rpm. The minimum inhibitory concentration of microencapsulated gallic acid (62.5 µg/ml) was significantly improved when compared with that of the original drug (>750 µg/ml). The anti-A. niger activity of gallic acid -containing microcapsules was much stronger than that of the original drug. Following 48 h of treatment, skin cell survival was approximately 90% with agarose/gelatin microcapsules containing gallic acid, whereas cell viability was only 25-35% with free gallic acid. Our results demonstrate that agarose/gelatin-based microcapsules containing gallic acid may prove to be helpful in the treatment of A. niger-induced skin infections near intravenous injection sites.


Subject(s)
Antifungal Agents/pharmacology , Aspergillosis/drug therapy , Aspergillus niger/growth & development , Dermatomycoses/drug therapy , Gallic Acid/pharmacology , Gelatin/pharmacology , Sepharose/pharmacology , Antifungal Agents/chemistry , Capsules , Cells, Cultured , Drug Evaluation, Preclinical , Gallic Acid/chemistry , Gelatin/chemistry , Humans , Keratinocytes/cytology , Keratinocytes/metabolism , Sepharose/chemistry
17.
J Microencapsul ; 31(8): 754-8, 2014.
Article in English | MEDLINE | ID: mdl-24963963

ABSTRACT

l-ascorbic acid is an abundant water-soluble nutrient found in vegetables and fruits. It enhances the cell proliferation, which is helpful in wound healing process. However, it is relatively unstable and easily degraded under external environments including acidity, alkalinity, evaporation, heat, oxidization, light or moisture. Its storage remains challenged. This study reported the development of l-ascorbic acid microcapsules using the natural protein, gelatin, and the natural polysaccharide, agar, as the wall protection carrier. The physical properties including entrapment efficiency, particle size, surface morphology, chemical compositions and release profile were identified. The cell proliferation of l-ascorbic acid microcapsules was stronger than the free drug. Significant cell growth in microencapsulated l-ascorbic acid-treated human epithelial HaCaT cells was observed when compared with untreated control. Since cell proliferation and wound repair are closely related, it is believed that l-ascorbic acid microcapsules would effectively increase the potential effect of wound healing activity in human skin.


Subject(s)
Antioxidants/pharmacology , Ascorbic Acid/pharmacology , Cell Proliferation/drug effects , Epithelial Cells/metabolism , Wound Healing/drug effects , Ascorbic Acid/chemistry , Capsules , Cell Line , Epithelial Cells/cytology , Humans
18.
J Biomech ; 47(10): 2430-5, 2014 Jul 18.
Article in English | MEDLINE | ID: mdl-24811044

ABSTRACT

We hypothesize that both compression and elongation stress-strain data should be considered for modeling and simulation of soft tissue indentation. Uniaxial stress-strain data were obtained from in vitro loading experiments of porcine liver tissue. An axisymmetric finite element model was used to simulate liver tissue indentation with tissue material represented by hyperelastic models. The material parameters were derived from uniaxial stress-strain data of compressions, elongations, and combined compression and elongation of porcine liver samples. in vitro indentation tests were used to validate the finite element simulation. Stress-strain data from the simulation with material parameters derived from the combined compression and elongation data match the experimental data best. This is due to its better ability in modeling 3D deformation since the behavior of biological soft tissue under indentation is affected by both its compressive and tensile characteristics. The combined logarithmic and polynomial model is somewhat better than the 5-constant Mooney-Rivlin model as the constitutive model for this indentation simulation.


Subject(s)
Liver/physiology , Animals , Anisotropy , Compressive Strength , Computer Simulation , Elasticity , Finite Element Analysis , Imaging, Three-Dimensional , Materials Testing , Models, Statistical , Stress, Mechanical , Swine , Tensile Strength
19.
Depress Res Treat ; 2014: 127632, 2014.
Article in English | MEDLINE | ID: mdl-24600517

ABSTRACT

Introduction. Despite the fact that maternal perinatal mental health problems have been extensively studied and addressed to be a significant health problem, the literature on paternal perinatal mental health problems is relatively scarce. The present study aims at determining the prevalence of paternal perinatal depression and identifying the risk factors and the relationship between antenatal and postpartum depression. Methodology. 622 expectant fathers were recruited from regional maternal clinics. The expectant fathers were assessed using standardized and validated psychological instruments on 3 time points including early pregnancy, late pregnancy, and six weeks postpartum. Results. Results showed that a significant proportion of expectant fathers manifested depressive symptoms during the perinatal period. Paternal antenatal depression could significantly predict higher level of paternal postpartum depression. Psychosocial risk factors were consistently associated with paternal depression in different time points. Conclusions. The present study points to the need for greater research and clinical attention to paternal depression given that it is a highly prevalent problem and could be detrimental to their spouse and children development. The present findings contribute to theoretical basis of the prevalence and risk factors of paternal perinatal depression and have implications of the design of effective identification, prevention, and interventions of these clinical problems.

20.
Colloids Surf B Biointerfaces ; 117: 277-83, 2014 May 01.
Article in English | MEDLINE | ID: mdl-24657927

ABSTRACT

Gelatin/Collagen-based matrix and reservoir nanoparticles require crosslinkers to stabilize the formed nanosuspensions, considering that physical instability is the main challenge of nanoparticulate systems. The use of crosslinkers improves the physical integrity of nanoformulations under the-host environment. Aldehyde-based fixatives, such as formaldehyde and glutaraldehyde, have been widely applied to the crosslinking process of polymeric nanoparticles. However, their potential toxicity towards human beings has been demonstrated in many previous studies. In order to tackle this problem, D-glucose was used during nanoparticle formation to stabilize the gelatin/collagen-based matrix wall and reservoir wall for the deliveries of Calendula officinalis powder and oil, respectively. In addition, therapeutic selectivity between malignant and normal cells could be observed. The C. officinalis powder loaded nanoparticles significantly strengthened the anti-cancer effect towards human breast adenocarcinoma MCF7 cells and human hepatoma SKHep1 cells when compared with the free powder. On the contrary, the nanoparticles did not show significant cytotoxicity towards normal esophageal epithelial NE3 cells and human skin keratinocyte HaCaT cells. On the basis of these evidences, D-glucose modified gelatin/collagen matrix nanoparticles containing C. officinalis powder might be proposed as a safer alternative vehicle for anti-cancer treatments.


Subject(s)
Calendula/chemistry , Collagen/chemistry , Drug Delivery Systems , Gelatin/chemistry , Glucose/chemistry , Nanoparticles/chemistry , Plant Extracts/pharmacology , Animals , Antineoplastic Agents/pharmacology , Cell Death/drug effects , Cell Survival/drug effects , Humans , Keratinocytes/cytology , Keratinocytes/drug effects , MCF-7 Cells , Nanoparticles/ultrastructure , Particle Size , Plant Oils/pharmacology , Powders , Spectroscopy, Fourier Transform Infrared , Sus scrofa
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