Life's simple 7 and cardiovascular disease risk knowledge in Hong Kong.

BACKGROUND: This study aimed at investigating the CV health and CV disease knowledge in terms of LS7 score among 3 age groups in Hong Kong. METHODS: A cross-sectional multicenter observational study was conducted to observe the CV health and disease risk knowledge in Hong Kong. Elderly subjects were recruited from 15 elderly centers, whereas young adults and the middle-aged were recruited from 6 on-campus health check sessions. Subjects' demographics, lifestyle behavior and risk knowledge were obtained through questionnaire while their body mass index, random capillary blood glucose, blood cholesterol and blood pressure were measured. LS7 score and risk knowledge score was calculated. RESULTS: The LS7 of younger adult, middle-aged and elderly were 10.6 ± 1.3, 9.3 ± 1.9 and 9.7 ± 1.7 respectively. Only 0.6% participants have attained ideal CV health and 35.9% have 5 to 7 ideal CV health metrics. Elderly performed worst in risk knowledge with a score of 8.1 ± 3.3 while young adult and middle-aged were similar (9.6 ± 1.8 and 9.7 ± 1.5). 71% of the participants correctly identified ≥9 components. Logistic regression revealed that subjects aged ≤65 years (OR 2.341, 95% CI 1.779 to 3.080) and with tertiary education (OR 2.031, 95% CI 1.527 to 2.701) were more likely to obtain optimum LS7. No association was found between having optimum LS7 and full knowledge. CONCLUSION: Only few adults in this study population had ideal CV health as defined by AHA. Knowledge has no association but young age and tertiary education has positive association with CV health.

Fluorescence excitation photography of epidermal cellular proliferation.

BACKGROUND: Fluorescence excitation provides the ability to interrogate innate molecules whose radiation emission correlates with specific functional states of tissue. OBJECTIVES: The present study demonstrates the effectiveness of a novel ultraviolet (UV) fluorescence excitation photography system in its ability to image rapidly proliferating epidermal skin lesions by capturing endogenous fluorescence emissions attributed to tryptophan. METHODS: A clinical prototype UV fluorescence excitation photography system was used to acquire images of endogenous fluorescence ascribed to tryptophan. RESULTS: Twelve human subjects and 11 ex vivo samples with various skin lesions consistently exhibited increased endogenous fluorescence at 340-nm wavelength upon excitation at 295 nm in rapid epidermal proliferations, including psoriasis, actinic keratoses and basal cell carcinoma, compared with surrounding normal skin. In contrast, nonproliferating lesions showed decreased fluorescence. CONCLUSIONS: This simple but robust point-and-shoot imaging system may offer a clinically useful, noncontact, noninvasive device for the diagnosis and detection of skin disease. As opposed to structural imaging modalities, fluorescence excitation imaging at 295/340-nm wavelengths offers high-sensitivity, wide-field functional imaging of cellular proliferation without the need for externally applied dyes or lengthy image processing. Furthermore, the image is instantly available and does not require interpretation or reconstruction.

Review of applications of fluorescence excitation spectroscopy to dermatology.

Endogenous molecules that exhibit fluorescence hold the potential to serve as reporters of tissue structure, activity and physiology. Fluorescence excitation spectroscopy is one means to measure and express tissue's innate fluorescence. This review focuses on the application of endogenous fluorescence ultraviolet excitation spectroscopy to dermatology.

Pharmacist intervention in the prevention of heart failure for high-risk elderly patients in the community.

BACKGROUND: Heart failure has become one of the major causes of hospitalization worldwide. Hypertension, diabetes mellitus and hyperlipidemia are the major causes of heart failure. In order to effectively prevent heart failure, blood pressure, blood glucose and cholesterol levels shall be closely monitored and controlled as well as medication adherence. This study aimed to investigate the role of pharmacist intervention in prevention of heart failure in high risk elderly patients in the community of Hong Kong. AIM: This study aimed to investigate the role of pharmacist intervention in prevention of heart failure in highrisk elderly patients in the community of Hong Kong. METHODS: This prospective uncontrolled study was conducted between July 2012 and April 2013 with two revisits every 3 to 4 months to review elderly patients' medication profiles as well as assess their blood pressure (BP), random capillary blood glucose (RCBG) level, cholesterol levels, signs and symptoms of heart failure and the compliance level. The results collected at the baseline data were analyzed and compared with those collected at the last follow-up visit. RESULT: A significant increase in number of subjects free of symptoms of heart failure (31.88%, p < 0.001) was found. For chronic disease management, significant reduction in LDL-cholesterol level (-0.86 ± 0.56mmol/L, p = 0.038) and triglyceride level (-1.15 ± 1.09mmol/L, p < 0.001) was observed in overall participants. Yet, no significant reduction in BP level or RCBG level was observed in overall subjects. Significant reduction in mean Morisky Medication Adherence Score (-0.54 ± 1.50, p = 0.005) indicated improvement in medication compliance in participants. CONCLUSION: The Pharmacy Outreach service has a significant role in prevention of heart failure, by means of minimizing heart failure symptoms, improving medication compliance and enhancing chronic disease management, particularly cholesterol management in community elderly patients. This study provided a reference for further investigation and evaluation of the role of pharmacists in preventing heart failure in the high-risk community elderly patients.

Cost-Effectiveness of Biosimilars vs Leflunomide in Patients With Rheumatoid Arthritis.

Importance: Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear. Objective: To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions. Design, Setting, and Participants: This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024. Interventions: The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate. Main Outcomes and Measures: Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort. Results: In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively. Conclusions and Relevance: In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

Risks of incident major osteoporotic fractures following SARS-CoV-2 infection among older individuals: a population-based cohort study in Hong Kong.

Population-based epidemiological studies on post-acute phase coronavirus 2019 (COVID-19)-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following SARS-CoV-2 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, and upper limb). COVID-19 patients were 1:1 matched to controls using propensity-score according to age, sex, vaccination status, medical comorbidities and baseline medications. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 429 459 COVID-19 patients were included, 1:1 matched to non-COVID individuals. Upon median follow-up of 11 months, COVID-19 patients had higher risks of major osteoporotic fractures (5.08 vs 3.95 per 1000 persons; HR 1.22 95%CI [1.15-1.31]), hip fractures (2.71 vs 1.94; 1.33 [1.22-1.46]), clinical vertebral fractures (0.42 vs 0.31; 1.29 [1.03-1.62]), and falls (13.83 vs 10.36; 1.28 [1.23-1.33]). Subgroup analyses revealed no significant interaction. In acute (within 30 days) and post-acute phases (beyond 30 days) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we consistently observed a significant increase in fractures and falls risks. Our study demonstrated increased risk of major osteoporotic fractures after SARS-CoV-2 infection in both acute and post-acute phases in older adults, partly due to increased fall risk. Clinicians should be aware of musculoskeletal health of COVID-19 survivors.

Our study showed that older individuals with coronavirus 2019 (COVID-19) infection are at a higher risk of suffering from major osteoporotic fractures, ie serious bone fractures related to osteoporosis, compared to those not infected. The study analyzed the health records of 429 459 patients aged 50 and older in Hong Kong who had been diagnosed with COVID-19 between January 2020 and March 2022. These patients were compared with a matched group without COVID-19, considering age, sex, vaccination status, medical comorbidities, and concomitant medications. Findings indicated that individuals who had contracted COVID-19 experienced a higher risk of major osteoporotic fractures, hip fractures, and clinical vertebral fractures. The risk of falls, a common cause of these fractures, was also higher in the COVID-19 group. This increased risk of major osteoporotic fractures and falls persists both shortly after infection and in the following months, underscoring the lasting impact of COVID-19 on the bone health of older adults. These results support the recommendations for the assessment of bone health and fall risks, and an urgent review of the requirement for interventions to reduce the risk of fragility fractures in older adult COVID-19 survivors.

Prediction of three-year outcome of renal transplantation from optimal donors versus expanded criteria donors.

BACKGROUND/AIMS: The shortage in organ supply has required the use of expanded criteria donors (ECD) for kidney transplantation. Current pre-transplant evaluations of ECD organs are based on histological, clinical or mixed criteria. This monocentric study investigates the predictivity of Karpinski's histological score on 3-year graft function in renal transplant. Ex-post classification using Nyberg's score was carried out to assess the reliability of a purely clinical score and its applicability for organ allocation. METHODS: We evaluated 407 deceased donors (251 optimal and 156 ECD) for renal transplants performed between 2001 and 2006. The differences in creatinine levels and MDRD-GFR at transplant and 1, 2 and 3 years post-transplant between optimal donors and ECD were recorded. Amongst ECD organs, the effect of different Karpinski score classes (0-1, 2, 3, 4, double transplants) on 3-year graft outcomes was analyzed. We then compared renal function over time across the Nyberg grades (A, B, C, and D). RESULTS: Karpinski scores 0-1 and 2 and double transplants were associated with improved graft function compared to scores 3 and 4. Nyberg's clinical score shows a good fit with medium-term outcome and Karpinski's score, but among the donors with a high Nyberg grade (C and D), it fails to differentiate between allocable or non-allocable organs (due to Karpinski's score ≥7). CONCLUSIONS: Our data demonstrate a correlation of histological damage at the time of transplant with 3-year graft function, but at present we are unable to provide any supposition on the possible outcome of the discarded kidneys.

Microbial interactions associated with secondary cucumber fermentation.

AIMS: To evaluate the interaction between selected yeasts and bacteria and associate their metabolic activity with secondary cucumber fermentation. METHODS AND RESULTS: Selected yeast and bacteria, isolated from cucumber secondary fermentations, were inoculated as single and mixed cultures in a cucumber juice model system. Our results confirmed that during storage of fermented cucumbers and in the presence of oxygen, spoilage yeasts are able to grow and utilize the lactic and acetic acids present in the medium, which results in increased brine pH and the chemical reduction in the environment. These conditions favour opportunistic bacteria that continue the degradation of lactic acid. Lactobacillus buchneri, Clostridium bifermentans and Enterobacter cloacae were able to produce acetic, butyric and propionic acids, respectively, when inoculated in the experimental medium at pH 4.6. Yeast and bacteria interactions favoured the survival of Cl. bifermentans and E. cloacae at the acidic pH typical of fermented cucumbers (3.2), but only E. cloacae was able to produce a secondary product. CONCLUSIONS: The methodology used in this study confirmed that a complex microbiota is responsible for the changes observed during fermented cucumber secondary fermentation and that certain microbial interactions may be essential for the production of propionic and butyric acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding the dynamics of the development of secondary cucumber fermentation aids in the identification of strategies to prevent its occurrence and economic losses for the pickling industry.

SGLT inhibitors for improving Healthspan and lifespan.

Sodium-glucose cotransporter inhibitor/inhibition (SGLTi), initially approved as a glucose-lowering therapy for type 2 diabetes, is associated with decreased risks for many of the most common conditions of aging, including heart failure, chronic kidney disease, all-cause hospitalization, atrial fibrillation, cancer, gout, emphysema, neurodegenerative disease/dementia, emphysema, non-alcoholic fatty liver disease, atherosclerotic disease, and infections. Studies also show that SGLTi improves overall life expectancy and reduces risks of cardiovascular death and cancer death. These wide-ranging health benefits are largely unexplained by the SGLTi's modest improvements in standard risk factors. SGLTi produces upregulation of nutrient deprivation signaling and downregulation of nutrient surplus signaling. This in turn promotes autophagy, which helps to optimize cellular integrity and prevent apoptotic cell death. SGLTi decreases oxidative stress and endoplasmic reticulum stress, restores of mitochondrial health, stimulates mitochondrial biogenesis, and diminishes proinflammatory and profibrotic pathways. These actions help to revitalize senescent cells, tissues, and organs. In summary, SGLTi appears to slow aging, prevent disease, and improve life expectancy, and its mechanisms of action lend strong biological plausibility to this hypothesis. Further randomized trials are warranted to test whether SGLTi, a safe and well-tolerated, once-daily pill, might improve healthspan and lifespan.

Impact of Introducing Infliximab Biosimilars on Total Infliximab Consumption and Originator Infliximab Prices in Eight Regions: An Interrupted Time-Series Analysis.

OBJECTIVE: We aimed to assess whether the introduction of the first infliximab biosimilar was associated with changes in overall infliximab consumption (originator and biosimilars) and price changes to the originator infliximab. METHODS: An interrupted time series analysis using infliximab sales data from 2010 to 2020 from the IQVIA Multinational Integrated Data Analysis System for eight selected regions: Australia, Canada, Hong Kong, Korea, India, Japan, the UK, and the USA. Quarterly measures of infliximab consumption and list prices were respectively defined as the number of standard units (SU)/1000 inhabitants and as 2020 USA dollars (USD)/SU. RESULTS: Following the introduction of infliximab biosimilars, overall infliximab consumption increased in Australia [immediate change: 0.145 SU/1000 inhabitants (P = 0.014); long-term change: 0.022 SU/1000 inhabitants per quarter (P < 0.001)], Canada [immediate change 0.415 (P = 0.008)], the UK [long-term change 0.024 (P < 0.001)], and Hong Kong [immediate change: 0.042 (P < 0.001)]. The list price of originator infliximab also decreased following biosimilar introduction in Australia [immediate change: - 187.84 USD/SU (P < 0.001); long-term change - 6.46 USD/SU per quarter (P = 0.043)], Canada [immediate change: - 145.58 (P < 0.001)], the UK [immediate change: - 34.95 (P = 0.010); long-term change: - 4.77 (P < 0.001)], and Hong Kong [long-term change: - 4.065 (P = 0.046)]. Consumption and price changes were inconsistent in India, Japan, Korea, and the USA. CONCLUSIONS: Introduction of the first infliximab biosimilar was not consistently associated with increased consumption across regions. Additional policy and healthcare system interventions to support biosimilar infliximab adoption are needed.

Monoclonal antibodies and Fc-fusion protein biologic medicines: A multinational cross-sectional investigation of accessibility and affordability in Asia Pacific regions between 2010 and 2020.

Background: Monoclonal antibody (mAb) and Fc-fusion protein (FcP) are highly effective therapeutic biologics. We aimed to analyse consumption and expenditure trends in 14 Asia-Pacific countries/regions (APAC) and three benchmark countries (the UK, Canada, and the US). Methods: We analysed 440 mAb and FcP biological products using the IQVIA-MIDAS global sales database. For each year between 2010 and 2020 inclusive, we used standard units (SU) sold per 1000 population and manufacture level price (standardised in 2019 US dollars) to evaluate consumption (accessibility) and expenditure (affordability). Changes of consumption and expenditure were estimated using compound annual growth rate (CAGR). Correlations between consumption, country's economic and health performance indicators were measured using Spearman correlation coefficient. Findings: Between 2010 and 2020, CAGRs of consumption in each region ranged from 7% to 34% and the CAGRs of expenditure ranged from 9% to 31%. The median consumption of biologics was extremely low in lower-middle-income economies (0·29 SU/1000 population) compared with upper-middle-income economies (1·20), high-income economies (40·94) and benchmark countries (109·55), although the median CAGRs of biologics consumption in lower-middle-income economies (31%) was greater than upper-middle-income (14%), high-income economies (13%) and benchmark countries (9%). Consumption was correlated with GDP per capita [Spearman's rank correlation coefficient (r) = 0·75, p < 0·001], health expenditure as a percentage of total (r = 0·83, p < 0·001) and medical doctors' density (r = 0·85, p < 0·001). Interpretation: There have been significant increases in mAb and FcP biologics consumption and expenditure, however accessibility of biological medicines remains unequal and is largely correlated with country's income level. Funding: This research was funded by NHMRC Project Grant GNT1157506 and GNT1196900; Enhanced Start-up Fund for new academic staff and Internal Research Fund, Department of Medicine, LKS Faculty of Medicine, University of Hong Kong.

Long-term health-related burden of adult congenital heart diseases in Hong Kong.

Aims: This study aimed to examine the long-term clinical and economic burden of adults with congenital heart disease (ACHD) in Hong Kong. Methods: It retrospectively analyzed 336 consecutive ACHD patients who attended the Adult Congenital Heart Clinic between January 1, 2009 and December 31, 2014. Direct medical costs and clinical outcomes over the 5 years were calculated and documented. The economic evaluation was from the hospital's perspective. Results: The median age of ACHD patients was 47 (31-62) years old, with female predominance (61.5%). Ventricular and atrial septal defects accounted for 70% and severe ACHD for 10% of the study cohort. The prevalence of arrhythmia and heart failure increased with the complexity of CHD. The total mean annual cost for managing each ACHD patient was USD 2,913. The annual cost of management of simple ACHD was USD 2,638 vs complex ACHD (USD 6,425) (p = 0.013). Conclusions: This study demonstrated severe ACHD patients accounted for higher cardiovascular morbidities in arrhythmias and heart failure with a higher cost of management.

Occurrence of Neospora caninum antibodies in capybaras (Hydrochaeris hydrochaeris) from São Paulo State, Brazil.

Capybara (Hydrochaeris hydrochaeris) is a large rodent distributed throughout tropical America. Antibodies to Neospora caninum in 213 feral capybaras from 11 counties of the State of São Paulo, Brazil, were assessed using the indirect immunofluorescent antibody test (titer >or=1:25) and found in 20 (9.4%), with titers of 1:25 in 4, 1:50 in 7, and 1:100 in 9 animals. This is the first report of occurrence of N. caninum antibodies in capybaras.

Effects of the myotoxic Lys49 phospholipase A2 from Agkistrodon contortrix laticinctus snake venom on water transport in the toad bladder epithelium: evidence for a role of microtubules and calmodulin.

ACLMT is a myotoxic Lys49 phospholipase A2 isolated from the venom of the snake Agkistrodon contortrix laticinctus. We have previously demonstrated that ACLMT affects the water transport in toad bladders through a mechanism partially mediated by an increase in the cytosolic calcium. This study aims to further investigate the sites and mechanisms involved in the effects of ACLMT on water transport in toad bladders by examining the role of microtubules and calmodulin. Water flow across the membrane was gravimetrically measured in bladder sac preparations. ACLMT increased basal water transport and inhibited water transport stimulated by vasopressin. Colchicine and trifluoperazine reduced the effect of the toxin on basal water transport and enhanced it on vasopressin-stimulated water transport. The results suggest that both microtubules and calmodulin may be involved in the effect of ACLMT on basal water transport. On the other hand, the effect of the toxin on vasopressin-stimulated water transport appears to be neither dependent on the microtubules integrity nor directly mediated by calmodulin. This study provides a deeper understanding of the effects of the Lys49 PLA2 myotoxins on membrane permeability, thus contributing to elucidate the toxicity mechanism of these myotoxins on biological tissues.

Clinical, humanistic, and economic outcomes between drug-eluting stent (DES) and bare metal stent (BMS): 18-month follow-up study.

BACKGROUND: Percutaneous coronary intervention (PCI) is one of the most performed interventions for ischemic heart diseases. In Hong Kong, the total number of patient discharges and deaths for ischemic heart diseases in 2009 was 33,363, including 4,360 deaths. There are over 5,000 cases of PCI yearly. This study aimed to compare clinical, economic, and humanistic outcomes among patients receiving drug-eluting stent (DES) or bare metal stent (BMS) in Hong Kong. METHODS: Patients who received stent implantation between September 15, 2009 and October 11, 2010 in Prince of Wales Hospital, Hong Kong, were recruited and followed for 18 months. Occurrence of major adverse cardiac events (cardiac death, non-fatal MI, TLR and TVR) was employed as the clinical outcome measurements. Improvement in quality-of-life by stent interventions was measured as quality-adjusted life-year (QALY). EQ-5D questionnaire was adopted to assess the QALY gained. Cost-utility analysis and cost-effectiveness analysis for BMS and DES were employed as the economic outcome measurement. RESULTS: Six hundred and eighty-four patients (DES = 402; BMS = 282) were included. From 0-18 months, TLR rate (2.7% vs 3.5%, p = .549) and TVR rate (3.7% vs 6.4%, p = .111) were lower in the DES group, but without statistical significance. EQ VAS (71.06 ± 14.56 vs 71.07 ± 16.57, p = .998) and utility score (0.81 ± 0.17 vs 0.78 ± 0.16, p = .162) were comparable between DES and BMS group. Overall, the cost per QALY gained was HKD + 1,178,100 and ICER was HKD + 187,000 (1USD = 7.8 HKD). CONCLUSIONS: No significant difference in TVR, TLR rates, EQ VAS, and utility score was found between the DES and BMS group. The higher cost of index procedure for the DES group was found to be partly offset by reduced cost of follow-up, offering cost-effectiveness in ACS patients, predominantly in STEMI patients. DES was recommended for STEMI patients.

Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.

T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)-specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8(+) T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.

Effect of a recombinant Lys49PLA2 myotoxin and Lys49PLA2-derived synthetic peptides from Agkistrodon species on membrane permeability to water.

The aim of this work was to study the effect of recombinant ACL myotoxin, a Lys49PLA2 from Agkistrodon contortrix laticinctus snake venom and Lys49PLA2-derived synthetic peptides corresponding to the region 115-129 of venom of the two different Agkistrodon species on water permeability in the toad urinary bladder. The water flow through the membrane was measured gravimetrically in bag preparations of the bladder. The addition of recombinant ACL myotoxin-MBP (maltose binding protein) fusion protein (10 nM) to the bathing solution significantly increased (above 60%) the water transport compared with the control hemibladders. The addition of the Lys49PLA2-derived synthetic peptides in several concentrations to the bathing solution did not affect the water transport across membrane. These results suggest that the ACL myotoxin effect on water transport is not related to the cytotoxic C-terminal region.

Effects of ACL myotoxin, a Lys49 phospholipase A(2) from Agkistrodon contortrix laticinctus snake venom, on water transport in the isolated toad urinary bladder.

ACL myotoxin (ACLMT) is a Lys49 phospholipase A(2)-like protein isolated from the venom of the snake Agkistrodon contortrix laticinctus. The aim of this work was to study the effect of ACLMT on water transport in the toad bladder. Water flow through the membrane was measured gravimetrically in bag preparations of the bladder. ACLMT (20 nM) increased the baseline water flow and partially inhibited arginine-vasopressin (AVP), 8-chlorophenylthio-cAMP (8-CPT-cAMP) and forskolin-stimulated water flow. The effect of ACLMT on baseline or AVP-stimulated water flow was prevented by lanthanum (0.1 mM) indicating that the effect of ACLMT on water transport may be mediated through an increase in intracellular calcium. The effect of ACLMT on baseline water flow was also prevented by nifedipine (0.1 mM) indicating the participation of exogenous calcium in this effect. Carbachol (0.1 mM) has been shown to enhance baseline water flow while inhibiting AVP-stimulated water flow. The effects of ACLMT and carbachol on baseline water flow and AVP-stimulated water flow were not additive, suggesting that both agents alter water transport by a similar mechanism. Indomethacin (10 microM) reduced the effect of ACLMT on forskolin-stimulated water flow, suggesting an increase in prostaglandin biosynthesis. These results suggest that the effects of ACLMT on water transport may be mediated by increasing intracellular calcium and stimulation prostaglandin biosynthesis.