Surgical treatment of constrictive pericarditis at a single center: 10 years of experience.

BACKGROUND: Constrictive pericarditis (CP) is a pericardial disease characterized by the pericardium becoming calcified or fibrotic as a result of chronic inflammation, which impairs diastolic filling by compressing the cardiac chambers. Pericardiectomy is a promising surgical option for treating CP. In this study, we reviewed over 10 years of preoperative, perioperative, and short-term postoperative follow-ups of patients who underwent pericardiectomy for constrictive pericarditis at our clinic. METHODS: Between January 2012 and May 2022, 44 patients were diagnosed with constrictive pericarditis. Twenty-six patients underwent pericardiectomy for CP. Median sternotomy is the surgical approach of choice because it provides easy access for complete pericardiectomy. RESULTS: The patient median age was 56 (min: 32, max: 71), and 22 out of 26 patients (84.6%) were male. Twenty-one patients (80.8%) complained of dyspnea, which was the most common reason for admission. Twenty-four patients (92.3%) were scheduled for elective surgery. Cardiopulmonary bypass (CPB) was used during the procedure in six patients (23%). The duration of intensive care stay was two days (min: 1, max: 11), and the total hospitalization was six days (min: 4, max: 21). No in-hospital mortality was observed. CONCLUSION: The median sternotomy approach provides a critical advantage in terms of performing a complete pericardiectomy. Although CP is a chronic condition, early diagnosis and planning of pericardiectomy before irreversible deterioration of cardiac function leads to a notable reduction in mortality and morbidity.

A rare case of septic pulmonary embolism in co-existence with infective endocarditis and COVID-19.

Infective endocarditis (IE) symptoms including fever, fatigue, dyspnea and myalgia are similar in COVID-19 findings. Therefore, the diagnosis of IE may be missed in patients with COVID-19. Co-existence with IE in COVID-19 is rarely reported. However, to our knowledge, only one case of septic pulmonary embolism in COVID-19 and IE was reported. Here, we describe a case of septic embolism due to tricuspid endocarditis caused by intravenous drug use in patients with COVID-19. In this fatal case, the use of prophylactic anticoagulants due to COVID-19 probably caused the tendency to hemorrhagic cerebrovascular complications. Our report emphasizes the complexity of anticoagulant prophylaxis in patients with COVID-19 which may cause hypercoagulopathy in co-existence with IE.

Development of a microfluidic platform to maintain viability of micro-dissected tumor slices in culture.

One of the issues limiting the development of personalized medicine is the absence of realistic models that reflect the nature and complexity of tumor tissues. We described a new tissue culture approach that combines a microfluidic chip with the microdissected breast cancer tumor. "Tumor-on-a-chip" devices are suitable for precision medicine since the viability of tissue samples is maintained during the culture period by continuously feeding fresh media and eliminating metabolic wastes from the tissue. However, the mass transport of oxygen, which arguably is the most critical nutrient, is rarely assessed. According to our results, transportation of oxygen provides satisfactory in vivo oxygenation within the system. A high level of dissolved oxygen, around 98%-100% for every 24 h, was measurable in the outlet medium. The microfluidic chip system developed within the scope of this study allows living and testing tumor tissues under laboratory conditions. In this study, tumors were generated in CD-1 mice using MDA-MB-231 and SKBR-3 cell lines. Microdissected tumor tissues were cultured both in the newly developed microfluidic chip system and in conventional 24-well culture plates. Two systems were compared for two different types of tumors. The confocal microscopy analyses, lactate dehydrogenase release, and glucose consumption values showed that the tissues in the microfluidic system remained more viable with respect to the conventional well plate culturing method, up to 96 h. The new culturing technique described here may be superior to conventional culturing techniques for developing new treatment strategies, such as testing chemotherapeutics on tumor samples from individual patients.

High-altitude illness: Management approach.

In high altitudes, usually above 2500 m, travelers are faced with decreased partial pressure of oxygen along with decreased barometric pressure. High-altitude illness, a syndrome of acute mountain sickness, high-altitude cerebral edema and high-altitude pulmonary edema, occurs due to the hypobaric hypoxia when there is inadequate acclimatization. This review provides detailed information about pathophysiology, clinical features, prevention and treatment strategies for high-altitude illness according to the current literature.

Analysis of the effects of COHb, lactate, and troponin levels on the clinical process and outcome in patients who were admitted to the emergency service due to carbon monoxide poisoning.

OBJECTIVE: The aim of the present study was to determine the demographic, medical, and treatment characteristics of patients followed up with the diagnosis of carbon monoxide (CO) poisoning in emergency care and also to determine the relationship of these patients' clinical process and outcome between carboxyhemoglobin (COHb), lactate, and troponin levels. METHODS: The present study was conducted retrospectively between 01/01/2013 and 01/01/2016 by examining 450 patients who were referred to the emergency service for CO poisoning. The ages; sexualities; manners of application; clinical findings; levels of blood COHb, lactate, and troponin; applied oxygen treatment method; and outcome of patients were evaluated. Data analysis was done by Shapiro-Wilk, Student's t, Mann-Whitney U, and chi-square tests. RESULTS: A total of 450 patients were included in the study. The median age of the patients was 35 (interquartile range (IQR) 26.75-45.00) years. In the study where data are not homogeneously distributed, the median levels of COHb, lactate, and troponin were 11.80% (IQR 3-23), 1.60 (IQR 1.10-2.5) mmol/l, and 0.00 (IQR 0.000-0.003) ng/ml, respectively. The levels of lactate were detected to be statistically high in patients who had syncope and who received hyperbaric oxygen treatment (p<0.05). In addition, the levels of lactate and troponin were significantly higher in patients who were hospitalized (p<0.05). CONCLUSION: The levels of COHb, lactate, and troponin can provide an insight to the clinician about hospitalization and the type of treatment.

Pharmacologic anisocoria due to nebulized ipratropium bromide: A diagnostic challenge.

Anisocoria may be physiological or seen in fatal conditions, such as intracranial hemorrhage. Newly developing anisocoria may cause confusion and diagnostic difficulty in the emergency department (ED). A 35-year-old female was admitted to the ED with an asthma attack and dyspnea. On examination, the patient was observed to have bilateral rhonchi and was treated with nebulized albuterol (salbutamol) and ipratropium bromide. After the treatment, the dyspnea improved, and mydriasis developed in the left eye (left pupil diameter 9 mm, right 4 mm). An examination revealed that the left pupil was dilated and unreactive to light, but there was no neurological finding. Afterwards, the patient reported that, during the treatment, some aerosol had leaked from the left side of the mask and may have come into contact with her left eye. Given this information, a pilocarpine test was performed, and the patient was diagnosed with pharmacologic anisocoria. The pupil returned to normal within 24 h. Ipratropium bromide is a drug frequently used in patients presenting to the ED with dyspnea. During treatment, nebulized ipratropium may leak from the edge of the facial mask into the ipsilateral eye and may cause mydriasis. A pilocarpine test can be used to differentiate pharmacological anisocoria from other causes, such as third nerve palsy and Adie's pupil. Through the awareness of emergency physicians and the use of the pilocarpine test, a diagnosis can be made without engaging in time-consuming and costly analyses. In addition, this complication can be prevented using masks that better fit the face, as well as protective goggles or eye patches, during treatment.

A new therapeutic combination for osteosarcoma: Gemcitabine and Clofazimine co-loaded liposomal formulation.

Osteosarcoma is the most common cancer in bone. Drug resistance is a challenge of current treatments that needs to be improved with novel treatment strategies. In this research, a new dual drug delivery system was developed with Gemcitabine (GEM) and Clofazimine (CLF) co-loaded liposome formulations. GEM is a well-known anticancer agent and CLF is a leprostatic and anti-inflammatory drug recently recognized as effective on cancer. GEM and CLF co-loaded liposomal formulation was achieved with compartmentalization as hydrophilic GEM being in core and lipophilic CLF sequestering in lipid-bilayer. Liposomes had high encapsulation efficiency (above 90%, GEM and above 80%, CLF). CLF release was enhanced while GEM release was slowed down in co-loaded liposomes compared to single cases. GEM/CLF co-loaded liposomes significantly enhanced cytotoxicity than GEM or CLF loaded liposomes on osteosarcoma cell line. CLF and GEM had synergistic effect (CI < 1). Results of flow cytometry showed higher apoptotic cell ratio, caspase-3 activity, mitochondrial membrane depolarized cells' ratio for GEM/CLF co-loaded liposome treatments than other liposomes. Cytotoxicity of CLF on bone cancer cells and also its synergistic effect with GEM on osteosarcoma is reported for the first time with this study. CLF's loading with GEM into liposome was also a new approach for enhancement of anticancer effect on Saos-2 cells. Therefore, GEM/CLF co-loaded liposomal delivery system is proposed as a novel approach for treatment of osteosarcoma.

Structure-based design, synthesis and anticancer effect of cyclic Smac-polyarginine peptides.

The second mitochondria-derived activator of caspase (Smac/DIABLO) is a pro-apoptotic protein that released from mitochondria into the cytosol when cells undergo apoptosis. Smac promotes caspase activation by binding the inhibitors of apoptosis proteins (IAP), particularly XIAP and eliminating their inhibitory activity. Although the seven N-terminal amino acids AVPIAQK (SmacN7) of Smac protein is able to elicit an anticancer response by itself, it is neither cell-permeable nor stable in the cellular environment. Thus, the use of SmacN7 derivatives and mimetics is an alluring field for cancer therapy. In this study, heptamer Smac peptide was fused to a well-known octaarginine cell-penetrating peptide for promoting its intracellular access. Both therapeutic Smac part and cell-penetrating octaarginine parts of the peptide sequence constrained in a cyclic structure so as to enhance the apoptosis-inducing potential of the SmacN7 peptide. Biological assays interestingly showed that cyclic peptides P4, P5 and P7 gave rise to a significant level of cytotoxicity and apoptosis mediated cell death in multiple myeloma tumor cells (MM) comparing to linear peptide.

In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma.

Drug repurposing has been proved to be an effective strategy to meet the urgent need for novel anticancer agents for multiple myeloma (MM) treatment. In this work, we aimed to investigate the anticancer effect and mechanism of tricyclic antidepressant nortriptyline (NTP) on the U266 MM cell line. The in vitro inhibitory effect of NTP at various doses and time points was studied. The combination potential of cisplatin-NTP was also investigated. Cell cycle analysis and three flow cytometric apoptosis assays were performed. NTP showed dose- and time-dependent inhibitory effects on the U266 MM cell line. NTP had greater inhibitory effect than cisplatin (IC50 26 µM vs. 40 µM). The cisplatin-NTP combination is antagonistic. In addition to G2/M phase cell cycle arrest, NTP induced apoptosis as indicated by mitochondrial membrane potential and caspase-3 and annexin V assays. NTP has inhibitory and apoptotic effects on U266 MM cells. The cisplatin-NTP combination indicated strong antagonism, which may have significant clinical relevance since antidepressants are commonly employed in adjuvant therapy for cancer patients. Based on these findings, the therapeutic potential of NTP for MM treatment should be investigated with in-depth mechanistic studies and in vivo experiments.

Peptidomic characterization and bioactivity of Protoiurus kraepelini (Scorpiones: Iuridae) venom.

Protoiurus kraepelini is a scorpion species found in parts of Turkey and Greece. In this study, the peptide profile of its venom was determined for the first time. The electrophoretic profile of the crude venom showed a protein distribution from 2 to 130 kDa. MALDI-TOF MS analysis of the venom peptide fraction yielded 27 peptides between 1059 and 4623 Da in mass. Several ion channelblocking and antimicrobial peptides were identified by peptide mass fingerprinting analysis. Cytotoxic and antimicrobial effects of the venom were also demonstrated on Jurkat cells and Escherichia coli, respectively. As the first peptidomic characterization study on P. kraepelini venom, this report lays the foundation for detailed future studies that may lead to the discovery of novel bioactive peptides.

Circulating LL37 targets plasma extracellular vesicles to immune cells and intensifies Behçet's disease severity.

Behçet's disease (BD) activity is characterised by sustained, over-exuberant immune activation, yet the underlying mechanisms leading to active BD state are poorly defined. Herein, we show that the human cathelicidin derived antimicrobial peptide LL37 associates with and directs plasma extracellular vesicles (EV) to immune cells, thereby leading to enhanced immune activation aggravating BD pathology. Notably, disease activity was correlated with elevated levels of circulating LL37 and EV plasma concentration. Stimulation of healthy PBMC with active BD patient EVs induced heightened IL1ß, IFNα, IL6 and IP10 secretion compared to healthy and inactive BD EVs. Remarkably, when mixed with LL37, healthy plasma-EVs triggered a robust immune activation replicating the pathology inducing properties of BD EVs. The findings of this study could be of clinical interest in the management of BD, implicating LL37/EV association as one of the major contributors of BD pathogenesis. Abbreviations: BD: Behçet's disease; EV: extracellular vesicle; BB: binding buffer; AnV: annexin V; autologEV: autologous extracellular vesicles; alloEV: allogeneic extracellular vesicles.

Anti-cancer effect of clofazimine as a single agent and in combination with cisplatin on U266 multiple myeloma cell line.

Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high morbidity. Clofazimine (CLF) is an FDA-approved leprostatic, anti-tuberculosis, and anti-inflammatory drug that was previously shown to have growth suppression effect on various cancer types such as hepatocellular, lung, cervix, esophageal, colon, and breast cancer as well as melanoma, neuroblastoma, and leukemia. The objective of this study was to evaluate the anticancer effect and mechanism of CLF on U266 MM cell line. CLF (10µM, 24h) treatment resulted up to 72% growth suppression on a panel of hematological cell lines. Dose-response study conducted on U266 MM cell line revealed an IC50 value of 9.8±0.7µM. CLF also showed a synergistic inhibition effect in combination with cisplatin. In mechanistic assays, CLF treatment caused mitochondrial membrane depolarization, change in cell membrane asymmetry and increase in caspase-3 activity; indicating to an intrinsic apoptosis mechanism. This study provides new evidence for the anticancer effect of CLF on U266 cell line. Further in vivo and clinical studies are warranted to evaluate its therapeutic potential for MM treatment.

Determination of the chest wall thicknesses and needle thoracostomy success rates at second and fifth intercostal spaces: a cadaver-based study.

INTRODUCTION: The purposes of this study were to measure the chest wall thicknesses (CWTs) at second intercostal space (ICS) mid-clavicular line (MCL) and fifth ICS MAL directly, and compare the actual success rates of needle thoracostomies (NTs) by inserting a 5-cm-long syringe needle. Predictive values of weight, body mass index (BMI) and CWT were also analyzed. MATERIALS AND METHODS: This study included 199 measurements of 50 adult fresh cadavers from both hemithoraces. Five-centimeter-long syringe needles were inserted and secured. Penetration into the pleural cavity was assessed, and CWTs at 4 locations were measured. Achieved power of this study for the primary aim of CWT comparison from 2nd and 5th ICSs was .94. RESULTS: Overall mean CWTs at 2nd ICS MCL and 5th ICS MAL were measured as 2.46 ± 0.78 and 2.89 ± 1.09, respectively, and 5th ICS MAL was found to be statistically thicker (P = .002). The success rate of NT at 2nd ICS MCL was 87% (95% CI, 80-94), and that at 5th ICS MAL was 78% (95% CI, 70-86; P = .3570). Only 6 (17.1%) of 35 failed NTs had a CWT greater than 5-cm. Needle thoracostomy has failed in 29 (14.9%) of 194 locations, despite a CWT less than 5-cm. Below a weight of 72 kg, BMI of 23 kg/m2, or CWT of 2.4 cm, all NTs were successful. DISCUSSION AND CONCLUSIONS: In this report, we present the largest cadaver-based cohort to date to the best of our knowledge, and we observed a statistically nonsignificant 9% more NT success rate at 2nd ICS at a power of 88% and statistically significant more success rate in males at 5th ICS was (47.7%). We also observed thinner CWTs and higher success rates than previous imaging-based studies. A BMI of 23 kg/m2 or less and weight of 72 kg or less seem to accurately rule-out NT failure in cadavers, and they seem to be better predictors at the bedside.

Assessment of ventricular wall motion with focused echocardiography during cardiac arrest to predict survival.

OBJECTIVES: Our primary goal is to investigate the hypothesis that in patients with a detectable ventricular wall motion (VWM) in cardiac ultrasonography (US) during cardiopulmonary resuscitation (CPR), survival rate is significantly more than in patients without VWM in US. MATERIAL AND METHODS: In our prospective, single center study, 129 adult cardiac arrest (CA) patients were enrolled. Cardiac US according to Focus Assessed Transthoracic Echo (FATE) protocol was performed before CPR. Presence of VWM was recorded on forms along with demographic data, initial rhythm, CA location, presence of return of spontaneous circulation (ROSC) and time until ROSC was obtained. RESULTS: 129 patients were included. ROSC was obtained in 56/77 (72.7%) patients with VWM and 3/52 (5.8%) patients without VWM which is statistically significant (p > 0.001). Presence of VWM is 95% (95% CI: 0.95-0.99) sensitive and 70% (95% CI: 0.58-0.80) specific for ROSC. 43/77 (55.8%) patients with VWM and 1 (1.9%) of 52 patients without VWM survived to hospital admission which was statistically significant (p < 0.001). Presence of VWM was 100% (95% CI: 0.87-1.00) sensitive and 54% (95% CI: 0.43-0.64) specific for survival to hospital admission. CONCLUSION: No patient without VWM in US survived to hospital discharge. Only 3 had ROSC in emergency department and only 1 survived to hospital admission. This data suggests no patient without VWM before the onset of CPR survived to hospital discharge and this may be an indication to end resuscitative efforts early in these patients.

Epidermal growth factor receptor-targeted immunoliposomes for delivery of celecoxib to cancer cells.

Cyclooxygenase-2 (COX-2) is highly expressed in many different cancers. Therefore, the inhibition of the COX-2 pathway by a selective COX-2 inhibitor, celecoxib (CLX), may be an alternative strategy for cancer prevention and therapy. Liposomal drug delivery systems can be used to increase the therapeutic efficacy of CLX while minimizing its side effects. Previous studies have reported the encapsulation of CLX within the non-targeted long circulating liposomes and functional effect of these formulations against colorectal cancer cell lines. However, the selectivity and internalization of CLX-loaded liposomes can further be improved by grafting targeting ligands on their surface. Cetuximab (anti-epidermal growth factor receptor - EGFR - monoclonal antibody) is a promising targeting ligand since EGFR is highly expressed in a wide range of solid tumors. The aim of this study was to develop EGFR-targeted immunoliposomes for enhancing the delivery of CLX to cancer cells and to evaluate the functional effects of these liposomes in cancer cell lines. EGFR-targeted ILs, having an average size of 120nm, could encapsulate 40% of the CLX, while providing a sustained drug release profile. Cell association studies have also shown that the immunoliposome uptake was higher in EGFR-overexpressing cells compared to the non-targeted liposomes. In addition, the CLX-loaded-anti-EGFR immunoliposomes were significantly more toxic compared to the non-targeted ones in cancer cells with EGFR-overexpression but not in the cells with low EGFR expression, regardless of their COX-2 expression status. Thus, selective targeting of CLX with anti-EGFR immunoliposomes appears to be a promising strategy for therapy of tumors that overexpress EGFR.

Characterization of Leiurus abdullahbayrami (Scorpiones: Buthidae) venom: peptide profile, cytotoxicity and antimicrobial activity.

BACKGROUND: Scorpion venoms are rich bioactive peptide libraries that offer promising molecules that may lead to the discovery and development of new drugs. Leiurus abdullahbayrami produces one of the most potent venoms among Turkish scorpions that provokes severe symptoms in envenomated victims. METHODS: In the present study, the peptide profile of the venom was investigated by electrophoretic methods, size-exclusion and reversed-phase chromatography and mass spectroscopy. Cytotoxic and antimicrobial effects were evaluated on a breast cancer cell line (MCF-7) and various bacterial and fungal species. RESULTS: Proteins make up approximately half of the dry weight of L. abdullahbayrami crude venom. Microfluidic capillary electrophoresis indicated the presence of 6 to 7 kDa peptides and proved to be a highly practical peptidomics tool with better resolution when compared to conventional polyacrylamide gel electrophoresis. Mass spectroscopy analysis helped us to identify 45 unique peptide masses between 1 to 7 kDa with a bimodal mass distribution peaking between molecular weights of 1 to 2 kDa (29%) and 3 to 4 kDa (31%). L. abdullahbayrami crude venom had a proliferative effect on MCF-7 cells, which may be explained by the high concentration of polyamines as well as potassium and calcium ions in the arachnid venoms. Antimicrobial effect was stronger on gram-negative bacteria. CONCLUSIONS: This work represents the first peptidomic characterization of L. abdullahbayrami venom. Considering the molecular weight-function relationship of previously identified venom peptides, future bioactivity studies may lead to the discovery of novel potassium and chloride ion channel inhibitors as well as new antimicrobial peptides from L. abdullahbayrami venom.

Characterization of Leiurus abdullahbayrami (Scorpiones: Buthidae) venom: peptide profile, cytotoxicity and antimicrobial activity

Background Scorpion venoms are rich bioactive peptide libraries that offer promising molecules that may lead to the discovery and development of new drugs.Leiurus abdullahbayrami produces one of the most potent venoms among Turkish scorpions that provokes severe symptoms in envenomated victims.Methods In the present study, the peptide profile of the venom was investigated by electrophoretic methods, size-exclusion and reversed-phase chromatography and mass spectroscopy. Cytotoxic and antimicrobial effects were evaluated on a breast cancer cell line (MCF-7) and various bacterial and fungal species.Results Proteins make up approximately half of the dry weight of L. abdullahbayrami crude venom. Microfluidic capillary electrophoresis indicated the presence of 6 to 7 kDa peptides and proved to be a highly practical peptidomics tool with better resolution when compared to conventional polyacrylamide gel electrophoresis. Mass spectroscopy analysis helped us to identify 45 unique peptide masses between 1 to 7 kDa with a bimodal mass distribution peaking between molecular weights of 1 to 2 kDa (29%) and 3 to 4 kDa (31%). L. abdullahbayrami crude venom had a proliferative effect on MCF-7 cells, which may be explained by the high concentration of polyamines as well as potassium and calcium ions in the arachnid venoms. Antimicrobial effect was stronger on gram-negative bacteria.Conclusions This work represents the first peptidomic characterization of L. abdullahbayrami venom. Considering the molecular weight-function relationship of previously identified venom peptides, future bioactivity studies may lead to the discovery of novel potassium and chloride ion channel inhibitors as well as new antimicrobial peptides fromL. abdullahbayrami venom.(AU)

Characterization of Leiurus abdullahbayrami (Scorpiones: Buthidae) venom: peptide profile, cytotoxicity and antimicrobial activity

Background Scorpion venoms are rich bioactive peptide libraries that offer promising molecules that may lead to the discovery and development of new drugs.Leiurus abdullahbayrami produces one of the most potent venoms among Turkish scorpions that provokes severe symptoms in envenomated victims.Methods In the present study, the peptide profile of the venom was investigated by electrophoretic methods, size-exclusion and reversed-phase chromatography and mass spectroscopy. Cytotoxic and antimicrobial effects were evaluated on a breast cancer cell line (MCF-7) and various bacterial and fungal species.Results Proteins make up approximately half of the dry weight of L. abdullahbayrami crude venom. Microfluidic capillary electrophoresis indicated the presence of 6 to 7 kDa peptides and proved to be a highly practical peptidomics tool with better resolution when compared to conventional polyacrylamide gel electrophoresis. Mass spectroscopy analysis helped us to identify 45 unique peptide masses between 1 to 7 kDa with a bimodal mass distribution peaking between molecular weights of 1 to 2 kDa (29%) and 3 to 4 kDa (31%). L. abdullahbayrami crude venom had a proliferative effect on MCF-7 cells, which may be explained by the high concentration of polyamines as well as potassium and calcium ions in the arachnid venoms. Antimicrobial effect was stronger on gram-negative bacteria.Conclusions This work represents the first peptidomic characterization of L. abdullahbayrami venom. Considering the molecular weight-function relationship of previously identified venom peptides, future bioactivity studies may lead to the discovery of novel potassium and chloride ion channel inhibitors as well as new antimicrobial peptides fromL. abdullahbayrami venom.

Thermodynamics and kinetics of association of antibiotics with the aminoglycoside acetyltransferase (3)-IIIb, a resistance-causing enzyme.

The thermodynamic and kinetic properties of interactions of antibiotics with the aminoglycoside acetyltransferase (3)-IIIb (AAC) are determined with several experimental methods. These data represent the first such characterization of an enzyme that modifies the 2-deoxystreptamine ring common to all aminoglycoside antibiotics. Antibiotic substrates for AAC include kanamycin A, kanamycin B, tobramycin, sisomicin, neomycin B, paromomycin, lividomycin A, and ribostamycin. Kinetic studies show that kanamycin group aminoglycosides have higher k(cat) values than members of the neomycin group. Only small aminoglycosides without intraring constraints show substrate inhibition. Isothermal titration calorimetry (ITC) and fluorescence measurements are consistent with a molecular size-dependent stoichiometry where binding stoichiometries are 1.5-2.0 for small antibiotics and 1.0 for larger. Antibiotic-enzyme interaction occurs with a favorable enthalpy (DeltaH < 0) and a compensating unfavorable entropy (TDeltaS < 0). The presence of coenzyme A significantly increases the affinity of the antibiotic for AAC. However, the thermodynamic properties of its ternary complexes distinguish this enzyme from other aminoglycoside-modifying enzymes (AGMEs). Unlike other AGMEs, the enthalpy of binding becomes more favored by 1.7-10.0-fold in the presence of the cosubstrate CoASH, while the entropy becomes 2.0-22.5-fold less favored. The overall free energy change is still only 1.0-1.9 kcal/mol from binary to ternary for all antibiotics tested, which is similar to those for other aminoglycoside-modifying enzymes. A computationally derived homology model provides structural support for these conclusions and further indicates that AAC is likely a member of the GCN5-related acetyltransferase family of proteins.