Exosomes are cell-secreted nano-sized vesicles which deliver diverse biological molecules for intercellular communication. Due to their therapeutic potential, exosomes have been engineered in numerous ways for efficient delivery of active pharmaceutical ingredients to various target organs, tissues, and cells. In vivo administered exosomes are normally delivered to the liver, spleen, kidney, lung, and gastrointestinal tract and show rapid clearance from the blood circulation after systemic injection. The biodistribution and pharmacokinetics (PK) of exosomes can be modulated by engineering various factors such as cellular origin and membrane protein composition of exosomes. Recent advances accentuate the potential of targeted delivery of engineered exosomes even to the most challenging organs including the central nervous system. Major breakthroughs have been made related to various imaging techniques for monitoring in vivo biodistribution and PK of exosomes, as well as exosomal surface engineering technologies for inducing targetability. For inducing targeted delivery, therapeutic exosomes can be engineered to express various targeting moieties via direct modification methods such as chemically modifying exosomal surfaces with covalenton-covalent bonds, or via indirect modification methods by genetically engineering exosome-producing cells. In this review, we describe the current knowledge of biodistribution and PK of exosomes, factors determining the targetability and organotropism of exosomes, and imaging technologies to monitor in vivo administered exosomes. In addition, we highlight recent advances in strategies for inducing targeted delivery of exosomes to specific organs and cells.

BACKGROUND: Tracheal intubation is closely associated with increases in intraocular pressure (IOP); however, the effects of double-lumen tube (DLT) intubation on IOP have not been validated. Systemic hypertension (HTN) is another factor that may increase IOP. In this study, we observed differences in IOP increases between DLT and single-lumen tube (SLT) intubation, and evaluated the influence of underlying HTN during rapid sequence induction.METHODS: Sixty-eight patients were allocated into one of the following group: SLT/without HTN (n = 17), SLT/HTN (n = 17), DLT/without HTN (n = 17), and DLT/HTN (n = 17). An SLT was inserted for orthopedic or gynecological surgery, and a DLT was inserted for lung surgery after rapid sequence induction using succinylcholine. IOP was measured before anesthetic induction and until 10 min after intubation using a handheld tonometer (Tono-Pen AVIA®).RESULTS: In the DLT/without HTN and DLT/HTN groups, the maximum increases in IOPs after tracheal intubation were 7.9 and 12.2 mmHg, respectively, compared to baseline. In the SLT/without HTN and SLT/HTN groups, the maximum increases were 5.0 and 4.9 mmHg, respectively, compared to baseline. In comparisons between patients with and without underlying HTN, the values of IOPs were comparable.CONCLUSIONS: Tracheal intubation with a DLT is associated with more increases in IOPs than with an SLT in rapid sequence induction. Well-controlled underlying hypertension did not increase IOP during tracheal intubation.
Female ; Gynecologic Surgical Procedures ; Humans ; Hypertension ; Intraocular Pressure ; Intubation ; Intubation, Intratracheal ; Lung ; Orthopedics ; Succinylcholine

Exosomes are cell-secreted nano-sized vesicles which deliver diverse biological molecules for intercellular communication. Due to their therapeutic potential, exosomes have been engineered in numerous ways for efficient delivery of active pharmaceutical ingredients to various target organs, tissues, and cells. In vivo administered exosomes are normally delivered to the liver, spleen, kidney, lung, and gastrointestinal tract and show rapid clearance from the blood circulation after systemic injection. The biodistribution and pharmacokinetics (PK) of exosomes can be modulated by engineering various factors such as cellular origin and membrane protein composition of exosomes. Recent advances accentuate the potential of targeted delivery of engineered exosomes even to the most challenging organs including the central nervous system. Major breakthroughs have been made related to various imaging techniques for monitoring in vivo biodistribution and PK of exosomes, as well as exosomal surface engineering technologies for inducing targetability. For inducing targeted delivery, therapeutic exosomes can be engineered to express various targeting moieties via direct modification methods such as chemically modifying exosomal surfaces with covalenton-covalent bonds, or via indirect modification methods by genetically engineering exosome-producing cells. In this review, we describe the current knowledge of biodistribution and PK of exosomes, factors determining the targetability and organotropism of exosomes, and imaging technologies to monitor in vivo administered exosomes. In addition, we highlight recent advances in strategies for inducing targeted delivery of exosomes to specific organs and cells.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) has long been recognized as a random phenomenon. Recent studies, however, suggest that activation sequence during atrial fibrillation is not entirely disorganized and organized activations as the transitional rhythm exists in the process of conversion from atrial fibrillation to atrial flutter. The purpose of this study is to characterize the process and significance of transitional rhythm during conversion of atrial fibrillation to atrial flutter. MATERIALS AND METHODS: In 9 patients with paroxysmal atrial fibrillation, 13 episodes that atrial fibrillation spontaneously converted to atrial flutter during electrophysiological study were analyzed. To map the right atrium (RA), 10 bipolar Halo catheter was positioned in the lateral free wall of the RA and multielectrode catheters were positioned in the coronary sinus, high RA, and His bundle area, respectively. Calculation of cycle length (CL) was performed with digital caliper during atrial fibrillation and atrial flutter. Direction of activation sequences was compared between transitional rhythm and following atrial flutter. RESULTS: During conversion of atrial fibrillation to atrial flutter, characteristic findings were observed as follows. 1) There was a gradual increase in atrial fibrillation cycle length before transitional rhythm. 2) A pause appeared in atrial fibrillation immediately prior to transitional rhythm, and between transitional rhythm and following atrial flutter. 3) Direction of activation sequences of the transitional rhythm to atrial flutter was concordant in 9 episodes and discordant in 4 episodes. 4) Spontaneous termination of atrial flutter (n=3) was also preceded by organized rhythm showing different sequence of activations from those of atrial flutter. CONCLUSION: A stereotypical pattern of activation sequence exists in the process of conversion of atrial fibrillation to atrial flutter. The occurrence of transitional rhythm influences the activation sequence of atrial flutter. Spontaneous termination of atrial flutter also preceded by transiently changing pattern of activation.
Atrial Fibrillation* ; Atrial Flutter* ; Bundle of His ; Catheters ; Coronary Sinus ; Heart Atria ; Humans

BACKGROUND AND PURPOSE: Left ventricular hypertrophy (LVH) is a well known cardiovascular risk factor, independent of hypertension, even in the absence of epicardial coronary artery disease. Possible mechanisms have been proposed, including increased LV mass, reduced coronary flow reserve (CFR) and diastolic filling abnormalities. However, the relations among LV hypertrophy, diastolic function, hypertension and coronary flow reserve (CFR) in patients with chest pain and normal coronary angiograms have not been well defined. SUBJECTS AND METHOD: Twenty-six patients with chest pain and normal coronary angiograms were included. LV mass, isovolumic relaxation time (IVRT), deceleration time (DT) and E/A ratio were assessed by 2-D echo-cardiography. Coronary blood flow velocity before and after intracoronary adenosine were measured using intracoronary Doppler wire (FIoWire). CFR was defined as ratio of peak flow velocity after adenosine to baseline flow velocity. Subjects were devided into 4 groups according to presence of LVH and hypertension and the parameters were compared among groups. RESULTS: FR was lower (p<0.01) in the groups with either hypertension or LVH or both than in the groups without them. The decrement in CFR was not linearly related to the degree of LVH (r=0.31, p=0.135). Although there were modest increment in IVRT and DT and decrement in E/A ratio in the groups with hypertension or LVH or both, there was no statistical significance. CONCLUSION: These findings suggest that the underlying mechanism of impaired CFR in patients with LVH or hypertension may be the consequence of primary coronary microvascular lesion rather than the process of left ventricular hypertrophy.
Adenosine ; Blood Flow Velocity ; Chest Pain* ; Coronary Artery Disease ; Deceleration ; Humans ; Hypertension ; Hypertrophy ; Hypertrophy, Left Ventricular ; Relaxation ; Risk Factors ; Thorax*

BACKGROUND AND OBJECTIVES: Atrioventricular block (AVB) is frequently seen following atrio-His (AH) interval lengthening after adenosine injection during sinus rhythm when both the fast and slow pathways are blocked in patients with dual atrioventricular nodal physiology (DAVNP). However, the condition also occurs in patients without DAVNP. Therefore, an AH jump may not indicate DAVNP if AVB is accompanied. The goal of this study was to use a low dose (6-9 mg) of adenosine to determine whether an AH jump truly represents DAVNP when the presence or absence of AVB following the AH jump is taken into consideration. SUBJECTS AND METHODS: This study included 78 patients (male:female=47:31, age 40.0+/-15.7 years, DAVNP group, n=46, control group, n=32). Adenosine (6-9 mg) was administered intravenously during sinus rhythm. The inclusion criteria of DAVNP were either induced AVNRT (n=37:common type, n=35, uncommon, n=2) or identification of AH jump (n=9) during elctrophysiology study (EPS). The control group consisted of patients without evidence of DAVNP and noninducible AVNRT on EPS. In all subjects, the electrophysiologic parameters of the AV nodal properties were tested. In the DAVNP group, intravenous adenosine during sinus rhythm resulted in an AH jump without AVB (8/46, 17.4%), an AH jump followed by AVB (9/46, 19.6%), an AH jump accompanied by induced AVNRT (1/46, 2.1%), or no significant changes in the AH interval (28/46, 60.9%). In the control group, none of the subjects showed an AH jump without AVB, however an AH jump with subsequent AVB was observed in 4 of 32 subjects (12.5%). If the finding of an AH jump without AVB alone was considered as a positive criteria of DAVNP, its specificity (87.5% to 100%) and positive predictive value (81.8% to 100%) increased compared to the criteria defined by an AH jump regardless of the presence or absence of AVB, however, its sensitivity decreased from 39.1% to 19.6%. CONCLUSION: AH jump induced by adenosine injection may not indicate DAVNP if AVB follows.
Adenosine* ; Atrioventricular Block ; Diagnosis* ; Heart Block ; Humans ; Physiology* ; Sensitivity and Specificity ; Tachycardia, Atrioventricular Nodal Reentry