Development of reverse-transcription loop-mediated isothermal amplification assays for point-of-care testing of human influenza virus subtypes H1N1 and H3N2

Influenza A virus (IAV) is the most widespread pathogen causing human respiratory infections. Although polymerase chain reaction (PCR)–based methods are currently the mostcommonly used tools for IAV detection, PCR is not ideal for point-of-care testing. In thisstudy, we aimed to develop a more rapid and sensitive method than PCR-based tools todetect IAV using loop-mediated isothermal amplification (LAMP) technology. We designedreverse-transcriptional (RT)–LAMP primers targeting the hemagglutinin gene. RNAs fromreference H1N1 and H3N2 showed specific RT-LAMP signals with the designed primers.We optimized the reaction conditions and developed universal reaction conditions for bothLAMP assays. Under these conditions, the detection limit was 50 copies for both RT-LAMPassays. There was no non-specific signal to 19 non-IAV respiratory viruses, such as influenza B virus, coronaviruses, and respiratory syncytial viruses. Regarding the reaction time, apositive signal was detected within 25 min after starting the reaction. In conclusion, ourRT-LAMP assay has high sensitivity and specificity for the detection of the H1 and H3 subtypes, making it suitable for point-of-care IAV testing.

Molecular Epidemiology of Ciprofloxacin-Resistant Escherichia coli Isolated from Community-Acquired Urinary Tract Infections in Korea

Background@#Escherichia coli is the predominant causative pathogen for community-acquired urinary tract infections (UTIs), and the increase in fluoroquinolone-resistant E. coli is of great concern in Korea. The objectives of this study were to investigate the genotypic characteristics and molecular epidemiology of ciprofloxacin-resistant (CIP-R) E. coli isolated from community-acquired UTIs in Korea. @*Materials and Methods@#E. coli samples isolated from the blood or urine were collected from patients with community-acquired acute pyelonephritis aged 15 years and more who were admitted to 12 Korean hospitals from 1st April 2010 to 29th February 2012. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase and plasmidmediated quinolone resistance determinants were performed for CIP-R E. coli isolates. @*Results@#A total of 569 E. coli isolates were collected, and 122 (21.4%) isolates were CIP-R isolates. The most prevalent sequence type (ST) was ST131 (28.7%, 35/122), followed by ST393 (14.7%, 18/122), ST1193 (13.1%, 16/122), ST38 (9.0%, 11/122), and ST405 (8.2%, 10/122). The antimicrobial resistance rates of ST131 to cefepime (22.9%, 8/35), ST38 to gentamicin (100%, 11/11), and ST405 to cefotaxime (66.7%, 6/9) were significantly higher than the resistance rates of all other STs combined. Notably, 40% (4/10) of ST405 clones produced extendedspectrum β-lactamases and were co-resistant to trimethoprim/sulfamethoxazole. aac(6′)-1b-cr (20%, 7/35) and CTX-M-14 (40%, 4/10) were more frequently observed in ST131 and ST405 compared with other clones, respectively. @*Conclusions@#Among the CIP-R uropathogenic E. coli isolates in this study, ST131, ST38, and ST405 were specifically associated with antimicrobial resistance.

Usefulness of Blood Cultures and Radiologic Imaging Studies in the Management of Patients with Community-Acquired Acute Pyelonephritis

BACKGROUND: The objective of this study was to examine the usefulness of blood cultures and radiologic imaging studies for developing therapeutic strategies in community-acquired acute pyelonephritis (CA-APN) patients. MATERIALS AND METHODS: We prospectively collected the clinical data of CA-APN patients who visited 11 hospitals from March 2010 to February 2011. RESULTS: Positive urine and blood cultures were obtained in 69.3% (568/820) and 42.7% (277/648), respectively, of a total of 827 CA-APN patients. Blood culture identified the urinary pathogen in 60 of 645 (9.3%) patients for whom both urine and blood cultures were performed; the organisms isolated from urine were inconsistent with those from blood in 11 and only blood cultures were positive in 49 patients. Final clinical failure was more common in the bacteremic patients than the non-bacteremic ones (8.0% vs. 2.7%, P = 0.003), as was hospital mortality (3.6% vs. 0.3%, P = 0.003). Likewise, durations of hospitalization and fever were significantly longer. Bacteremia was independent risk factor for mortality (OR 9.290, 1.145-75.392, P = 0.037). With regard to radiologic studies, the detection rate of APN was 84.4% (445/527) by abdominal computed tomography and 40% (72/180) by abdominal ultrasonography. Eighty-one of 683 patients (11.9%) were found to have renal abscess, perinephric abscess, urolithiasis, hydronephorosis/hydroureter or emphysematous cystitis, which could potentially impact on clinical management. Patients with Pitt score ≥ 1, flank pain or azotemia were significantly more likely to have such structural abnormalities. CONCLUSION: Blood cultures are clinically useful for diagnosis of CA-APN, and bacteremia is predictive factor for hospital mortality. Early radiologic imaging studies should be considered for CA-APN patients with Pitt scores ≥1, flank pain or azotemia.

Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Clinical and Microbiologic Characteristics of Clostridium difficile Infection Caused by Binary Toxin Producing Strain in Korea

BACKGROUND: Binary toxin-producing Clostridium difficile infections (CDI) are known to be more severe and to cause higher case fatality rates than those by binary toxin-negative isolates. There has been few data of binary toxin-producing CDI in Korea. Objective of the study is to characterize clinical and microbiological trait of CDI cause by binary-toxin producing isolates in Korea. MATERIALS AND METHODS: From September 2008 through January 2010, clinical characteristics, medication history and treatment outcome of all the CDI patients were collected prospectively. Toxin characterization, PCR ribotyping and antibiotic susceptibility were performed with the stool isolates of C. difficile. RESULTS: During the period, CDI caused by 11binary toxin-producing isolates and 105 toxin A & toxin B-positive binary toxin-negative isolates were identified. Comparing the disease severity and clinical findings between two groups, leukocytosis and mucoid stool were more frequently observed in patients with binary toxin-positive isolates (OR: 5.2, 95% CI: 1.1 to 25.4, P = 0.043; OR: 7.6, 95% CI: 1.6 to 35.6, P = 0.010, respectively), but clinical outcome of 2 groups did not show any difference. For the risk factors for acquisition of binary toxin-positive isolates, previous use of glycopeptides was the significant risk factor (OR: 6.2, 95% CI: 1.4 to 28.6, P = 0.019), but use of probiotics worked as an inhibitory factor (OR: 0.1, 95% CI: 0.0 to 0.8; P = 0.026). PCR ribotypes of binary toxinproducing C. difficile showed variable patterns: ribotype 130, 4 isolates; 027, 3 isolates; 267 and 122, 1 each isolate and unidentified C1, 2 isolates. All 11 binary toxin-positive isolates were highly susceptible to clindamycin, moxifloxacin, metronidazole, vancomycin and piperacillin-tazobactam, however, 1 of 11 of the isolates was resistant to rifaximin. CONCLUSIONS: Binary toxin-producing C. difficile infection was not common in Korea and those isolates showed diverse PCR ribotypes with high susceptibility to antimicrobial agents. Glycopeptide use was a risk factor for CDI by those isolates.

Epidemiology and Clinical Characteristics of Clostridium difficile Infection in a Korean Tertiary Hospital

In order to investigate the incidence, clinical and microbiologic characteristics of Clostridium difficile infection (CDI) in Korea, a prospective observational study was performed. From September 2008 through January 2010, all patients whose stool was tested for toxin assay A&B and/or C. difficile culture were studied for clinical characteristics. Toxin types of the isolates from stool were tested. The mean incidence of CDI per 100,000 patient-days was 71.6 by month (range, 52.5-114.0), and the ratio of CDI to antibiotic-associated diarrhea was 0.23. Among 200 CDI patients, 37.5% (75/200) was severe CDI based on severity score. Clinical outcome of 189 CDI was as followed; 25.9% (49/189) improved without treatment, 84.3% (118/140) achieved clinical cure and attributed mortality was 0.7% (1/140) with the treatment. Recurrence rate was 21.4% (30/140) and cure without recurrence was 66.4% (93/140). The most common type of toxin was toxin A-positive/toxin B-positive strain (77.5%), toxin A-negative/toxin B-positive strains or binary toxin-producing strains comprised 15.4% or 7.1%, respectively. In conclusion, the incidence of CDI in Korea is a little higher than other reports during the non-epidemic setting. We expect that the change of epidemiology and clinical severity in CDI can be evaluated based on these results.

Prevalence and Characterization of Plasmid-Medicated Quinolone Resistance Genes among Clinical Isolates of Extended-Spectrum Cephalosporin Resistant Enterobacter cloacae

BACKGROUND: Extended-spectrum cephalosporins (ESCs)-resistant Enterobacter cloacae is one of the pathogens of nosocomial infection the incidence of which is on the rise. Moreover, plasmid-mediated quinolone resistance genes (PMQR genes) that reduce quinolone sensitivity have been shown to be widely distributed among clinical isolates of Enterobacteriaceae. This study was carried out to observe the distribution of PMQR genes in clinical isolates of E. cloacae resistant to ESCs. MATERIALS AND METHODS: Fourty-three ESCs-resistant E. cloacae strains from the blood collected during the span of 7 years, from 1994 to 2001, at Seoul National University Children's Hospital (SNUCH) were included in this study. Isoelectric focusing and enzyme specific PCR were performed to characterize beta-lactamase. The presence of qnrA, qnrB, qnrC, qnrS, qepA, and aac(6')-Ib-cr was determined by PCR, restriction enzyme analyses of PCR products, and DNA sequencing. Minimal inhibitory concentration (MIC) of several quinolones was measured by agar dilution method. RESULTS: The PMQR genes were detected in 9 (21%) of 43 ESCs-resistant E. cloacae isolates. Among them, five isolates were positive for qnrB2, and each two isolates harbored qnrB4 or qnrB5, respectively. qnrA, qnrC, qnrS or qepA was not identified. aac(6')-Ib was detected in 27 isolates, but aac(6')-Ib-cr was not found. Among the 9 qnrB-positive isolates, 5 produced SHV-12, 3 were derepressed mutants, and 1 produced pI 7.5 beta-lactamase. MIC ranges and percent resistances of nalidixic acid, ofloxacin, levofloxacin, and moxifloxacin for the PMQR genes-positive isolates were higher than PMQR genes-negative isolates. CONCLUSION: In this study, ESCs-resistant E. cloacae showed a high prevalence of PMQR genes, and qnrB was the only PMQR gene identified.

Prevalence and Characterization of Plasmid-Medicated Quinolone Resistance Genes among Clinical Isolates of Extended-Spectrum Cephalosporin Resistant Enterobacter cloacae

BACKGROUND: Extended-spectrum cephalosporins (ESCs)-resistant Enterobacter cloacae is one of the pathogens of nosocomial infection the incidence of which is on the rise. Moreover, plasmid-mediated quinolone resistance genes (PMQR genes) that reduce quinolone sensitivity have been shown to be widely distributed among clinical isolates of Enterobacteriaceae. This study was carried out to observe the distribution of PMQR genes in clinical isolates of E. cloacae resistant to ESCs. MATERIALS AND METHODS: Fourty-three ESCs-resistant E. cloacae strains from the blood collected during the span of 7 years, from 1994 to 2001, at Seoul National University Children's Hospital (SNUCH) were included in this study. Isoelectric focusing and enzyme specific PCR were performed to characterize beta-lactamase. The presence of qnrA, qnrB, qnrC, qnrS, qepA, and aac(6')-Ib-cr was determined by PCR, restriction enzyme analyses of PCR products, and DNA sequencing. Minimal inhibitory concentration (MIC) of several quinolones was measured by agar dilution method. RESULTS: The PMQR genes were detected in 9 (21%) of 43 ESCs-resistant E. cloacae isolates. Among them, five isolates were positive for qnrB2, and each two isolates harbored qnrB4 or qnrB5, respectively. qnrA, qnrC, qnrS or qepA was not identified. aac(6')-Ib was detected in 27 isolates, but aac(6')-Ib-cr was not found. Among the 9 qnrB-positive isolates, 5 produced SHV-12, 3 were derepressed mutants, and 1 produced pI 7.5 beta-lactamase. MIC ranges and percent resistances of nalidixic acid, ofloxacin, levofloxacin, and moxifloxacin for the PMQR genes-positive isolates were higher than PMQR genes-negative isolates. CONCLUSION: In this study, ESCs-resistant E. cloacae showed a high prevalence of PMQR genes, and qnrB was the only PMQR gene identified.

Impact of Piperacillin/Tazobactam Use to Intestinal Colonization of Extended- spectrum-lactamase Producing Escherichia coli and Klebsiella pneumoniae

BACKGROUND: Being able to hydrolyze the majority of b-lactam antibiotics that are currently in use, extended-spectrum b-lactamases (ESBLs) pose a serious clinical problem. In order to solve this problem, it is recommended to use beta-lactam/beta-lactamase inhibitor instead of extended-spectrum cephalosporins. This study investigated the relationship between piperacillin/tazobactam use and ESBL-producing Klebsiella pneumoniae and Escherichia coli in stool colony. MATERIALS AND METHODS: A prospective study was performed in hemato-oncology department patients of Hanyang University Hospital. During the pre-intervention period of 3 months (Feb. 2005 to Apr. 2005), antibiotics were prescribed liberally. During the intervention period of 6 months (May. 2005 to Oct. 2005), use of the 3rd (4th) generation cephalosporins and carbapenems were restricted and piperacillin/tazobactam was recommended. All enrolled patients performed stool culture or rectal swab culture. ESBL confirmed by Double disk synergy test and commercial identification kit. Between the pre-intervention and intervention groups, acquisition rates of ESBL producing organisms were compared. RESULTS: 50 cases were enrolled in pre-intervention period and 112 cases were enrolled in intervention period. In intervention period, use of 3rd (4th) generation cephalosporins and carbapenems decreased from 27 daily define dose/1,000patient/days to 6.82 DDD/1,000patient/days, but use of piperacillin/tazobactam increased from 1.98 DDD/1,000patient/days to 5.66 DDD/1,000patient/days. The intestinal acquisition rate of ESBL producing organism decreased from 30% to 12%. There was no difference in overall mortality of infectious disease between two phase. CONCLUSION: Use of piperacillin/tazobactam instead of extended-spectrum cephalosporins reduces intestinal acquisition rate of ESBL producing K. pneumoniae and E. coli. Therefore, in order to decrease the number of ESBL producing organism, we recommend using piperacillin/tazobactam instead of using extended-spectrum cephalosporins.

Impact of Piperacillin/Tazobactam Use to Intestinal Colonization of Extended- spectrum-lactamase Producing Escherichia coli and Klebsiella pneumoniae

BACKGROUND: Being able to hydrolyze the majority of b-lactam antibiotics that are currently in use, extended-spectrum b-lactamases (ESBLs) pose a serious clinical problem. In order to solve this problem, it is recommended to use beta-lactam/beta-lactamase inhibitor instead of extended-spectrum cephalosporins. This study investigated the relationship between piperacillin/tazobactam use and ESBL-producing Klebsiella pneumoniae and Escherichia coli in stool colony. MATERIALS AND METHODS: A prospective study was performed in hemato-oncology department patients of Hanyang University Hospital. During the pre-intervention period of 3 months (Feb. 2005 to Apr. 2005), antibiotics were prescribed liberally. During the intervention period of 6 months (May. 2005 to Oct. 2005), use of the 3rd (4th) generation cephalosporins and carbapenems were restricted and piperacillin/tazobactam was recommended. All enrolled patients performed stool culture or rectal swab culture. ESBL confirmed by Double disk synergy test and commercial identification kit. Between the pre-intervention and intervention groups, acquisition rates of ESBL producing organisms were compared. RESULTS: 50 cases were enrolled in pre-intervention period and 112 cases were enrolled in intervention period. In intervention period, use of 3rd (4th) generation cephalosporins and carbapenems decreased from 27 daily define dose/1,000patient/days to 6.82 DDD/1,000patient/days, but use of piperacillin/tazobactam increased from 1.98 DDD/1,000patient/days to 5.66 DDD/1,000patient/days. The intestinal acquisition rate of ESBL producing organism decreased from 30% to 12%. There was no difference in overall mortality of infectious disease between two phase. CONCLUSION: Use of piperacillin/tazobactam instead of extended-spectrum cephalosporins reduces intestinal acquisition rate of ESBL producing K. pneumoniae and E. coli. Therefore, in order to decrease the number of ESBL producing organism, we recommend using piperacillin/tazobactam instead of using extended-spectrum cephalosporins.

The effects of tetracycline-HCl on SLA implant surface structure / 대한치주과학회지

The present study was performed to evaluate the effects of Tetracycline-HCl on the microstructure change of SLA implant surface according to application time. In the Tetracycline-HCl group, 6 implants were rubbed with sponges soaked 50mg/ml Tetracycline-HCl solution for 0.5min., 1min., 1.5min., 2min., 2.5min. and 3min. In the saline group, another 6 implants conditioned with sponges soaked saline using same methods. One implant wasn't conditioned anything. Then, the changes of surface roughness values were evaluated by optical interferometer & specimens were processed for scanning electron microscopic observation. The results of this study were as follows: 1. In both Tetracycline-HCl group & saline group, there are no significant differences between surface roughness values before & after surface detoxification. And in scanning electron microscopic observation, there are slightl9y changes of implant surface structures but this changes were not significant by comparison with no treatment implant surface. 2. In the changes of surface roughness values & the scanning electron microscopic observation, there were no significant differences between saline & Tetracycline-HCl groups. In conclusion, the detoxification with 50mg/ml Tetracycline-HCl within 3 minutes can be applied for treatment of peri-implantitis in SLA surface implants, without surface microstructure changes.

Mutant Prevention Concentration of Polymyxin B for the Clinical Isolates of Pseudomonas aeruginosa

BACKGROUND: Infection caused by multi-drug resistant (MDR) Gram-negative organisms such as Pseudomonas and Acinetobacter species is one of emerging important problems in modern hospitals. To treat multi-drug resistant non-fermenting Gram-negatives, polymyxins which were used in 1960s, but abandoned because of grave toxicities such as renal toxicity are reused. The objective of this study was to estimate the probability of resistance development of the clinical isolates of Pseudomonas aeruginosa to polymyxins. METHODS AND MATERIALS: Twenty-nine multidrug-resistant P. aeruginosa isolates were collected from Dankook University Hospital and Seoul National University Hospital in 2000 and tested for antimicrobial susceptibility test, minimal inhibitory concentration (MIC), mutant prevention concentration (MPC) and mutant frequency to ciprofloxacin and polymyxin B. RESULTS: The MIC50 and MIC90 of polymyxin B for the isolates were 2 and 2 microgram/mL, and those of ciprofloxacin were 0.5 and 4 microgram/mL, respectively. Thirteen of 29 isolates developed polymyxin B-resistant mutants but all 29 isolates, ciprofloxacin-resistant mutants. The MPC50 and MPC90 of polymyxin B were 32 and 64 microgram/mL, and those values of ciprofloxacin were 4 and 64 microgram/mL. Mutation frequencies of polymyxin B ranged from 2 x 10(-9) to 2 x 10(-7), and those of ciprofloxacin from 4 x 10(-10) to 5 x 10(-7). CONCLUSIONS: Mutation frequencies of polymyxin B were similar to those of ciprofloxacin, suggesting appreciable development of resistant mutants with wide usage of polymyxins.

Mutant Prevention Concentration of Polymyxin B for the Clinical Isolates of Pseudomonas aeruginosa

BACKGROUND: Infection caused by multi-drug resistant (MDR) Gram-negative organisms such as Pseudomonas and Acinetobacter species is one of emerging important problems in modern hospitals. To treat multi-drug resistant non-fermenting Gram-negatives, polymyxins which were used in 1960s, but abandoned because of grave toxicities such as renal toxicity are reused. The objective of this study was to estimate the probability of resistance development of the clinical isolates of Pseudomonas aeruginosa to polymyxins. METHODS AND MATERIALS: Twenty-nine multidrug-resistant P. aeruginosa isolates were collected from Dankook University Hospital and Seoul National University Hospital in 2000 and tested for antimicrobial susceptibility test, minimal inhibitory concentration (MIC), mutant prevention concentration (MPC) and mutant frequency to ciprofloxacin and polymyxin B. RESULTS: The MIC50 and MIC90 of polymyxin B for the isolates were 2 and 2 microgram/mL, and those of ciprofloxacin were 0.5 and 4 microgram/mL, respectively. Thirteen of 29 isolates developed polymyxin B-resistant mutants but all 29 isolates, ciprofloxacin-resistant mutants. The MPC50 and MPC90 of polymyxin B were 32 and 64 microgram/mL, and those values of ciprofloxacin were 4 and 64 microgram/mL. Mutation frequencies of polymyxin B ranged from 2 x 10(-9) to 2 x 10(-7), and those of ciprofloxacin from 4 x 10(-10) to 5 x 10(-7). CONCLUSIONS: Mutation frequencies of polymyxin B were similar to those of ciprofloxacin, suggesting appreciable development of resistant mutants with wide usage of polymyxins.

Differential changes in the expression of cyclic nucleotide phosphodiesterase isoforms in rat brains by chronic treatment with electroconvulsive shock

Electroconvulsive shock (ECS) has been suggested to affect cAMP signaling pathways to exert therapeutic effects. ECS was recently reported to increase the expression of PDE4 isoforms in rat brain, however, these studies were limited to PDE4 family in the cerebral cortex and hippocampus. Thus, for comprehensive understanding of how ECS regulates PDE activity, the present study was performed to determine whether chronic ECS treatment induces differential changes in the expression of all the PDE isoforms in rat brains. We analyzed the mRNA expression of PDE isoforms in the rat hippocampus and striatum using reverse transcription polymerase chain reaction. We found chronic ECS treatment induced differential changes in the expression of PDE isoform 1, 2, 3, 4, 5 and 7 at the rat hippocampus and striatum. In the hippocampus, the expression of PDE1A/B (694%), PDE4A (158%), PDE4B (323 %), and PDE4D (181%) isoforms was increased from the controls, but the expression of PDE2 (62.8%) and PDE7 (37.8%) decreased by chronic ECS treatment. In the striatum, the expression of PDE1A/B (179%), PDE4A (223%), PDE4B (171%), and PDE4D (327%) was increased by chronic ECS treatment with the concomitant decrease in the expression of PDE2 (78.4%) and PDE3A (67.1%). In conclusion, chronic ECS treatment induces differential changes in the expression of most PDE isoforms including PDE1, PDE2, PDE3, PDE4, PDE5, and PDE7 in the rat hippocampus and striatum in an isoform- and brain region-specific manner. Such differential change is suggested to play an important role in regulation of the activity of PDE and cAMP system by ECS.