Incidence of chemotherapy-related cardiac dysfunction in cancer patients.

BACKGROUND: Cancer patients are increasingly affected by chemotherapy-related cardiac dysfunction. The reported incidence of this condition vary significantly across different studies. HYPOTHESIS: A better comprehensive understanding of chemotherapy-related cardiac dysfunction incidence in cancer patients is imperative. Therefore, we performed a meta-analysis to establish the overall incidence of chemotherapy-related cardiac dysfunction in cancer patients. METHODS: We searched articles in PubMed and EMBASE from database inception to May 1, 2023. Studies that reported the incidence of chemotherapy-related cardiac dysfunction in cancer patients were included. RESULTS: A total of 53 studies involving 35 651 individuals were finally included in the meta-analysis. The overall pooled incidence of chemotherapy-related cardiac dysfunction in cancer patients was 63.21 per 1000 person-years (95% CI: 57.28-69.14). The chemotherapy-related cardiac dysfunction incidence increased steeply within half a year of cancer chemotherapy. Also, the trend of chemotherapy-related cardiac dysfunction incidence appeared to have plateaued after a longer duration of follow-up. In addition, chemotherapy-related cardiac dysfunction incidence rates are significantly higher among patients with age ≥50 years versus patients with age <50 years (99.96 vs. 34.48 per 1000 person-years). The incidence rate of cardiac dysfunction was higher among breast cancer patients (72.97 per 1000 person-years), leukemia patients (65.21 per 1000 person-years), and lymphoma patients (55.43 per 1000 person-years). CONCLUSION: Our meta-analysis unveiled a definitive overall incidence rate of chemotherapy-related cardiac dysfunction in cancer patients. In addition, it was found that the risk of developing this condition escalates within the initial 6 months postchemotherapy, subsequently tapering off to become statistically insignificant after a duration of 6 years.

[Identification of key points and differentiation planning strategies of Shantou, Guangdong, China]. / å¹¿ä¸œçœæ±•å¤´å¸‚ç”Ÿæ€ä¿®å¤å ³é”®ç‚¹è¯†åˆ«ä¸Žå·®å¼‚åŒ–è§„åˆ’.

Territorial ecological restoration planning is a carrier process for carrying out territorial space regulation and ecological restoration. However, current urban planning efforts only focus on ecological processes, and fail to coordinate the development of both ecology and society. Taking Shantou, a city in Guangdong Province, as an example, we focused on the identification of ecological restoration nodes and the development of differentiated planning strategies from a comprehensive ecological-social perspective. By considering ecosystem integrity, we extracted the ecological corridors and key points by identifying ecological sources and constructing resistance surfaces, constructed an ecological recreation service evaluation system from the social perspective in terms of recreational allocation and recreational value to identify key areas for recreation services, and obtained different types of ecological restoration strategies by synthesizing the results of ecology and recreation. The results showed that there were 136 ecological corridors and 77 ecological nodes in Shantou, with a total length of 380.58 km. The most important recreation areas were the coastline, several inland bays, and wetland tidal flats, with an area of 33.78 km2 and accounting for 1.6% of the total area. Low-level recreation areas was the largest, accounting for 57.3% of the total area. We proposed the composite strategy of "recreation expansion & fishery development", the connectivity strategy of "ecological construction & corridor connection", and the protection strategy of "vegetation restoration & development restriction". This study would provide a comprehensive analysis path for the ecological protection and restoration planning of coastal cities, and would help promote the practicality and maximizing the comprehensive benefits of territorial ecological restoration planning.

The role of glucocorticoids in increasing cardiovascular risk.

Introduction: Different studies provide conflicting evidence regarding the potential for glucocorticoids (GCs) to increase the risk of cardiovascular diseases. This study performed a systematic review and meta-analysis to determine the correlation between GCs and cardiovascular risk, including major adverse cardiovascular events (MACE), death from any cause, coronary heart disease (CHD), heart failure (HF), and stroke. Methods: We performed a comprehensive search in PubMed and Embase (from inception to June 1, 2022). Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Results: A total of 43 studies with 15,572,512 subjects were included. Patients taking GCs had a higher risk of MACE (RR = 1.27, 95% CI: 1.15-1.40), CHD (RR = 1.25, 95% CI: 1.11-1.41), and HF (RR = 1.92, 95% CI: 1.51-2.45). The MACE risk increased by 10% (95% CI: 6%-15%) for each additional gram of GCs cumulative dose or by 63% (95% CI: 46%-83%) for an additional 10 µg daily dose. The subgroup analysis suggested that not inhaled GCs and current GCs use were associated with increasing MACE risk. Similarly, GCs were linked to an increase in absolute MACE risk of 13.94 (95% CI: 10.29-17.58) cases per 1,000 person-years. Conclusions: Administration of GCs is possibly related with increased risk for MACE, CHD, and HF but not increased all-cause death or stroke. Furthermore, it seems that the risk of MACE increased with increasing cumulative or daily dose of GCs.

Gut microbe-derived milnacipran enhances tolerance to gut ischemia/reperfusion injury.

There are significant differences in the susceptibility of populations to intestinal ischemia/reperfusion (I/R), but the underlying mechanisms remain elusive. Here, we show that mice exhibit significant differences in susceptibility to I/R-induced enterogenic sepsis. Notably, the milnacipran (MC) content in the enterogenic-sepsis-tolerant mice is significantly higher. We also reveal that the pre-operative fecal MC content in cardiopulmonary bypass patients, including those with intestinal I/R injury, is associated with susceptibility to post-operative gastrointestinal injury. We reveal that MC attenuates mouse I/R injury in wild-type mice but not in intestinal epithelial aryl hydrocarbon receptor (AHR) gene conditional knockout mice (AHRflox/flox) or IL-22 gene deletion mice (IL-22-/-). Collectively, our results suggest that gut microbiota affects susceptibility to I/R-induced enterogenic sepsis and that gut microbiota-derived MC plays a pivotal role in tolerance to intestinal I/R in an AHR/ILC3/IL-22 signaling-dependent manner, revealing the pathological mechanism, potential prevention and treatment drugs, and treatment strategies for intestinal I/R.

Gut microbiota dysbiosis is associated with sepsis-induced cardiomyopathy in patients: A case-control study.

BACKGROUND: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. METHODS: A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). RESULTS: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. CONCLUSIONS: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.

Optimization of production process of Aeromonas veronii CA07 strain inactivated vaccine / 中国生物制品学杂志

@#Abstract：Objective To optimize the production process of inactivated vaccine of Aeromonas veronii（AV）CA07 strain. Methods The fermentation culture process of AV CA07 strain liquid was determined through the optimization of the culture time（2～16 h），medium（optimized fermentation medium，LB medium and NB medium）and fermentation conditions（in⁃ oculation amount of 1%，5%，10% and 15%；ventilation rate of 2，4，6 and 8 L／min and fermentation time of 6，8，10 and 12 h）. The optimal inactivation process was determined through the comparison of the final concentration of formalde⁃ hyde solution（0. 10%，0. 20%，0. 30% and 0. 40%），inactivation temperature（28 and 37 ℃）and inactivation time（24， 48 and 72 h）. The large⁃scale production process of inactivated vaccine of AV CA07 strain in 500 L fermentor was estab⁃ lished and the prepared vaccines were tested for safety and immunogenicity. Results The optimal inoculation amount of AV CA07 strain was 5%，ventilation rate was 4 L／min and culture time was 10 ~ 12 h. The optimal inactivation condition was adding formaldehyde solution with final concentration of 0. 30% incubating at 37 ℃ for 24 h. The number of viable bacteria in the fermentation broth of AV CA07 strain prepared in 500 L fermentor was more than 8 × 109 CFU／mL. All crucian carps immunized with the inactivated vaccine by abdomen survived. After challenge，the relative immune protection rate was more than 90%. Conclusion AV CA07 strain inactivated vaccine prepared by optimized production process showed good safety and immunogenicity.

Relationship between red blood cell distribution width-to-albumin ratio and outcome of septic patients with atrial fibrillation: a retrospective cohort study.

BACKGROUND: This retrospective cohort study aimed to investigate the association between red blood cell distribution width-to-albumin ratio (RAR) and in-hospital mortality in patients with sepsis and atrial fibrillation (AF). METHODS: Data were obtained from the Medical Information Mart for the Intensive Care Database IV database version 1.0. Multivariate Cox regression models, curve-fitting, and Kaplan-Meier analyses were performed to determine the correlation between RAR and in-hospital mortality in patients with sepsis and AF. RESULTS: This study included 3042 patients with sepsis and AF. Confounding variables were adjusted for in the Multivariable Cox regression analysis models. RAR was independently associated with in-hospital mortality (hazard ratio 1.06; 95% confidence interval 1.03-1.08; p < 0.001). A linear relationship was found between the RAR and in-hospital mortality in patients with sepsis and AF. CONCLUSION: Elevated RAR levels are associated with increased in-hospital mortality in patients with sepsis and AF. Further research is required to confirm this association.

The role of the cd99l2 gene on leukocyte interstitial migration in zebrafish.

Leukocytes play an essential role in ontogeny, tissue regeneration, and innate and adaptive immunity. The migration of leukocytes to the infected or traumatized areas is necessary for their immune response function. As an adhesion molecule, CD99L2 is crucial in the extravasation of leukocytes, however, its role in the interstitial migration of leukocytes remains unclear. In this study, the cd99l2 gene was knock-out by TALEN (transcription activator-like effector nuclease) in zebrafish and discovered that the deletion had no effect on zebrafish development. The number of granulocytes and macrophages recruited to the wounded tissue was significantly reduced in the cd99l2 mutants following caudal fin damage. Further research revealed that the expression of mfap4 was drastically decreased in the cd99l2 mutants, which may be one of the reasons that affect the migration of macrophages to the wound site. Moreover,transgenic lines with labeled vasculature, neutrophils and macrophages demonstrated that neutrophils and macrophages migrate throughout the interstitial space to the wound tissue in both wild-type and mutant zebrafish at 60 hours post-fertilization, indicating that the cd99l2 gene is involved in the interstitial migration of leukocytes. Finally, RNA transcription, protein folding, and the P450 pathway were enriched in cd99l2 mutants by RNA-seq analysis. Previous research had demonstrated that the regulation of transcription and signal transduction could be affected by adhesion molecules, which may suggest that the cd99l2 gene is involved in the cascade signaling pathway of leukocyte migration as an adhesion molecule. In conclusion, this study uncovered a novel function of the cd99l2 gene in the process of leukocyte migration in zebrafish, which is expected to provide a theoretical foundation for inflammatory and immune-related diseases.

Gut microbiota-derived indole 3-propionic acid partially activates aryl hydrocarbon receptor to promote macrophage phagocytosis and attenuate septic injury.

Sepsis is associated with a high risk of death, and the crosstalk between gut microbiota and sepsis is gradually revealed. Indole 3-propionic acid (IPA) is a gut microbiota-derived metabolite that exerts immune regulation and organ protective effects. However, the role of IPA in sepsis is not clear. In this study, the role of IPA in sepsis-related survival, clinical scores, bacterial burden, and organ injury was assessed in a murine model of cecal ligation and puncture-induced polymicrobial sepsis. Aryl hydrocarbon receptor (AhR) highly specific inhibitor (CH223191) was used to observe the role of AhR in the protection of IPA against sepsis. The effects of IPA on bacterial phagocytosis by macrophages were investigated in vivo and vitro. The levels of IPA in feces were measured and analyzed in human sepsis patients and patient controls. First, we found that gut microbiota-derived IPA was associated with the survival of septic mice. Then, in animal model, IPA administration protected against sepsis-related mortality and alleviated sepsis-induced bacterial burden and organ injury, which was blunted by AhR inhibitor. Next, in vivo and vitro, IPA enhanced the macrophage phagocytosis through AhR. Depletion of macrophages reversed the protective effects of IPA on sepsis. Finally, on the day of ICU admission (day 0), septic patients had significantly lower IPA level in feces than patient controls. Also, septic patients with bacteremia had significantly lower IPA levels in feces compared with those with non-bacteremia. Furthermore, in septic patients, reduced IPA was associated with worse clinical outcomes, and IPA in feces had similar prediction ability of 28-day mortality with SOFA score, and increased the predictive ability of SOFA score. These findings indicate that gut microbiota-derived IPA can protect against sepsis through host control of infection by promoting macrophages phagocytosis and suggest that IPA may be a new strategy for sepsis treatment.

Predicting prolonged postoperative length of stay risk in patients undergoing lumbar fusion surgery: Development and assessment of a novel predictive nomogram.

Objective: The purpose of this study was to develop and internally validate a prediction nomogram model in patients undergoing lumbar fusion surgery. Methods: A total of 310 patients undergoing lumbar fusion surgery were reviewed, and the median and quartile interval were used to describe postoperative length of stay (PLOS). Patients with PLOS > P75 were defined as prolonged PLOS. The least absolute shrinkage and selection operator (LASSO) regression was used to filter variables for building the prolonged PLOS risk model. Multivariable logistic regression analysis was applied to build a predictive model using the variables selected in the LASSO regression model. The area under the ROC curve (AUC) of the predicting model was calculated and significant test was performed. The Kappa consistency test between the predictive model and the actual diagnosis was performed. Discrimination, calibration, and the clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using the bootstrapping validation. Results: According to the interquartile range of PLOS in a total of 310 patients, the PLOS of 235 patients was ≤P75 (7 days) (normal PLOS), and the PLOS of 75 patients was > P75 (prolonged PLOS). The LASSO selected predictors that were used to build the prediction nomogram included BMI, diabetes, hypertension, duration of surgery, duration of anesthesia, anesthesia type, intraoperative blood loss, sufentanil for postoperative analgesia, and postoperative complication. The model displayed good discrimination with an AUC value of 0.807 (95% CI: 0.758-0.849, P < 0.001), a Kappa value of 0.5186 (cutoff value, 0.2445, P < 0.001), and good calibration. A high C-index value of 0.776 could still be reached in the interval validation. Decision curve analysis showed that the prolonged PLOS nomogram was clinically useful when intervention was decided at the prolonged PLOS possibility threshold of 3%. Conclusions: This study developed a novel nomogram with a relatively good accuracy to help clinicians access the risk of prolonged PLOS in lumbar fusion surgery patients. By an estimate of individual risk, surgeons and anesthesiologists may shorten PLOS and accelerate postoperative recovery of lumbar fusion surgery through more accurate individualized treatment.

Molecular characterization and functional analysis of IL-18 in snakehead (Channa argus) during Aeromonas schubertii and Nocardia seriolae infections.

As a proinflammatory cytokine of the interleukin-1 (IL-1) family, IL-18 plays important roles in host protection against bacterial, viral, and fungal infection. We cloned the open reading frame of snakehead (Channa argus) IL-18 (shIL-18) and found that it contained 609 base pairs and encoded 202 amino acid residues. The shIL-18 included a conserved IL-1-like family signature and two potential IL-1ß-converting enzyme cutting sites; one was conserved in all analyzed IL-18s, but the other was unique to shIL-18. Unlike other IL-18s, shIL-18 also contained a predicted signal peptide. In this study, shIL-18 was constitutively expressed in all tested tissues, and its expression was induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo and by lipoteichoic acid, lipopolysaccharides, and polyinosinic-polycytidylic acid in head kidney leukocytes in vitro. Moreover, recombinant shIL-18 upregulated the expression of interferon-γ, IL-1ß, and tumor necrosis factor-α1 and -α2 and promoted the proliferation of leukocytes. Taken together, these results showed that IL-18 played crucial roles in host defense against bacterial infection in fish, as it does in mammals.

Single-walled carbon nanotubes as delivery vehicles enhance the immunoprotective effect of an immersion DNA vaccine against infectious spleen and kidney necrosis virus in mandarin fish.

As a high mortality disease, Infectious spleen and kidney necrosis virus (ISKNV) can cause massive economic damage on mandarin fish farming industry in China, which seriously hindered the development of mandarin fish farming industry. In this research, SWCNTs (single-walled carbon nanotubes) as a candidate for DNA vaccine carrier was vaccinated by immersion (1, 2, 5, 10, 20 mg/L) in juvenile mandarin fish. In muscle, spleen and kidney tissues, the results showed that transcription and expression of MCP gene can be detected in pcDNA-MCP and SWCNTs-pcDNA-MCP groups after bath immunization. The immune response (immune-related genes expression, serum antibody production, enzyme activities and C3 content) was significantly enhanced in fish which vaccinated with SWCNTs-pcDNA-MCP in comparison with those vaccinated with pcDNA-MCP alone. After 14 d challenge, the RPS (relative percentage survival) can be enhanced which using SWCNTs as a carrier in SWCNTs-pcDNA-MCP (82.4%) group at 20 mg/L (the highest vaccine dose) than the naked pcDNA-MCP (54.2%) group. This study reveals that functionalized SWCNTs could be a promising immersion DNA vaccine carrier in aquaculture.

Immersion vaccination of Mandarin fish Siniperca chuatsi against infectious spleen and kidney necrosis virus with a SWCNTs-based subunit vaccine.

Infectious spleen and kidney necrosis virus (ISKNV) cause a high mortality disease which lead to significant economic loss on mandarin fish in China. There is no effective drug or vaccine against this fatal disease at present. Meanwhile, many drugs and vaccines had no effect in many cases account of several impenetrable barriers (cell, skin and gastrointestinal tract). Here we reported an immersion subunit vaccine system (SWCNTs-MCP) encoding MCP gene of ISKNV based on single-walled carbon nanotubes (SWCNTs). To evaluate its efficacy against ISKNV, we found a stronger and longer duration immune response (serum antibody production, enzyme activities and immune-related genes expression) can be induced in fish vaccinated with SWCNTs-MCP in comparison with those vaccinated with MCP alone. Importantly, SWCNTs can increase the immune protective effect of naked subunit vaccine by ca. 23.8%. Thereby, this study demonstrates that SWCNTs as a promising carrier for subunit vaccine might be used to vaccinate large-scale juvenile mandarin fish by bath administration approach.

Role of angiotensin II type 2 receptor during electrophysiological remodeling of left ventricular hypertrophic myocardium in spontaneously hypertensive rats.

The objective was to investigate the role of angiotensin II type 2 receptor during electrophysiological remodeling of left ventricular hypertrophic myocardium in spontaneously hypertensive rats (SHRs). A total of 36, aged 10 weeks, male SHRs were divided into three groups: control, valsartan, and valsartan + PD123319 groups (n = 12 in each). The systolic blood pressure, left ventricular mass index, ventricular effective refractory period, and ventricular fibrillation threshold (VFT) were also measured after 8 weeks. At the same time, INa, ICaL, Ito, and membrane capacitance were measured in left ventricular myocytes by whole-cell patch-clamp. The VFT of valsartan was higher than that of control (valsartan vs. CONTROL: 17.4 ± 0.6 mA vs. 15.8 ± 0.5 mA, P < .05). The VFT of valsartan was higher than that of valsartan + PD123319 (valsartan vs. valsartan + PD123319: 17.4 ± 0.6 mA vs. 16.6 ± 0.9 mA, P < .05). The density of Ito of valsartan was higher than that of control (valsartan vs. CONTROL: 14.7 ± 0.42 pA/pF vs. 11.2 ± 0.15 pA/pF, P < .05). The density of Ito of valsartan was higher than that of valsartan + PD123319 (valsartan vs. valsartan + PD123319: 14.7 ± 0.42 pA/pF vs. 13.6 ± 0.30 pA/pF, P < .05). The density of ICaL of valsartan was lower than that of control (valsartan vs. CONTROL: -4.6 ± 0.2 pA/pF vs. -6.9 ± 0.1 pA/pF, P < .05). The density of ICaL of valsartan was lower than that of valsartan + PD123319 (valsartan vs. valsartan + PD123319: -4.6 ± 0.2 pA/pF vs. -5.4 ± 0.1 pA/pF, P < .05). These results demonstrated that the stimulation of angiotensin II type 2 receptor improved electrophysiological remodeling of left ventricular hypertrophic myocardium in SHR.

Microwave-Assisted Regioselective Synthesis of 3-Functionalized Indole Derivatives via Three-Component Domino Reaction.

A microwave-assisted regioselective synthesis of 3-functionalized indole derivatives via a three-component domino reaction of anilines, arylglyoxal monohydrates, and cyclic 1,3-dicarbonyl compounds is described. The main advantages of this protocol are short reaction times, practical simplicity, its metal-free nature, the availability of starting materials, green solvents, and high regioselectivity.

Ruthenium-Catalyzed Carbonylation of Oxalyl Amide-Protected Benzylamines with Isocyanate as the Carbonyl Source.

An efficient synthesis of isoindolin-1-ones from oxalyl amide-protected benzylamines, through ruthenium-catalyzed intramolecular C(sp2)-H carbonylation, has been developed. Variously substituted benzylamines could be well tolerated in this new protocol, affording the corresponding products in moderate to excellent yields. This approach constitutes the first example of Ru(II)-catalyzed C(sp2)-H carbonylation with isocyanate as a novel commercially available carbonyl source.

Pd-Catalyzed regioselective sequential meta-, ortho-C-H functionalization of arenes: a predictable approach to the synthesis of polysubstituted ß-arylethylamines.

With the assistance of the same bidentate directing group, the first example of sequential, controllable C-H functionalization of ß-arylethylamines at different positions for the construction of polysubstituted arenes is reported. Pd-Catalyzed highly regioselective ortho-C-H functionalization reactions of meta-aryl substituted arylethylamines are performed, including alkynylation, iodination, acetoxylation and amination, which led to a concise approach to the synthesis of polysubstituted ß-arylethylamine derivatives.

An efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives under catalyst-free conditions.

A concise, efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives via a three-component reaction of 4-oxo-4H-chromene-3-carbaldehydes, malononitrile or cyanoacetates, and aromatic amines under catalyst-free conditions in an environmentally friendly medium (ethanol-water, 3:1 v/v) is described. This synthesis involves a group-assisted purification process, which avoids traditional recrystallization and chromatographic purification methods.

Design of a hydroxyapatite-binding antimicrobial peptide with improved retention and antibacterial efficacy for oral pathogen control.

Controlling and reducing the formation of pathogenic biofilm on tooth surface is the key to the prevention and treatment of the biofilm-associated oral diseases. Antimicrobial peptides (AMPs), considered as possible future alternatives for conventional antibiotics, have been extensively studied for the control of bacterial infection. Due to the rapid dilution and degradation by human saliva, AMP preparations designed for oral use with longer retention and higher efficacy are in urgent need. To this end, a hydroxyapatite (HAp)-binding antimicrobial peptide (HBAMP), which is based on the fusion of a specific HAp-binding heptapeptide (HBP7) domain and a broad-spectrum antimicrobial peptide (KSLW) domain, has been developed in our laboratory. HBAMP was supposed to form a contact-active antibacterial interface on tooth surface to inhibit the formation of biofilms. In this study, we investigated its binding behaviour, antibacterial activity against bacteria in both planktonic and sessile states, enzymatic stability in human saliva, and cytocompatibility to human gingival fibroblasts (HGFs). Our findings suggest that HBAMP could adsorb on tooth surface to provide effective antibacterial activity with improved retention. This study provides a proof-of-concept on using conjugated molecules to promote antibacterial efficacy by synergistically actions of HBAMP free in solution and bound on tooth surface.