Efficacy of fosfomycin compared to second generation cephalosporin flumarin as antimicrobial prophylaxis for transrectal ultrasound-guided prostate biopsy: a single center retrospective study.

BACKGROUND: Fluoroquinolone has been the historic choice of antimicrobial prophylaxis for transrectal ultrasound (TRUS) guided prostate biopsy. However, increased fluoroquinolone resistance and recent restrictions of its use for antimicrobial prophylaxis has led to the emergence of alternative agents for antimicrobial prophylaxis for TRUS guided prostate biopsy including fosfomycin and cephalosporins. This study aimed to compare the efficacy of fosfomycin and a second-generation cephalosporin flumarin as alternative antimicrobials for TRUS-guided prostate biopsy in terms of the incidence of infectious complications after TRUS-guided prostate biopsy. METHODS: A retrospective chart review of all patients who underwent TRUS-guided prostate biopsy between November 2009 to January 2023 was undertaken. Comparison of baseline characteristics and the incidence of infectious complications was done between those who received fosfomycin as antimicrobial prophylaxis for TRUS-guided prostate biopsy and those who received flumarin. Multivariate logistic regression analysis was conducted to identify risk factors for infectious complications after TRUS-guided prostate biopsy. RESULTS: Of 2,900 patients identified as eligible candidates for analysis, 333 (11.5%) received fosfomycin and 2,567 (88.5%) received flumarin. The overall rate of infectious complications was approximately 3% lower in patients who received fosfomycin, although such difference did not reach statistical significance (5.7% vs. 8.6%, p = 0.074). Multivariate logistic regression analysis showed that history of operation done under general anaesthesia within six months of the biopsy (odds ratio [OR]: 2.216; 95% confidence interval [CI]: 1.042-4.713; p = 0.039) and history of prior antimicrobial use within six months (OR: 1.457; 95% CI: 1.049-2.024; p = 0.025) were significant risk factors for infectious complications after TRUS-guided prostate biopsy. CONCLUSION: Fosfomycin was comparable to second-generation cephalosporin flumarin in preventing infectious complications after TRUS-guided prostate biopsy. Coupled with its properties such as ease of administration, low adverse effects, low resistance rate, and low collateral damage, fosfomycin might be an attractive alternative antimicrobial prophylaxis for TRUS-guided prostate biopsy.

Effect of Sedation Anesthesia With Intravenous Propofol on Transrectal Ultrasound-Guided Prostate Biopsy Outcomes.

BACKGROUND: Sedation anesthesia during transrectal ultrasound (TRUS)-guided prostate biopsy is known to decrease patient pain and anxiety, but little is known whether it affects the procedure's prostate cancer detection and complication rates. This study aimed to determine the effect of sedation anesthesia with intravenous (IV) propofol on TRUS-guided prostate biopsy outcomes. METHODS: A retrospective analysis of 2,119 patients who underwent TRUS-guided prostate biopsy between November 2009 and February 2019 was undertaken. The patients were divided into two groups: patients who underwent sedation anesthesia with IV propofol and patients who underwent local anesthesia with intrarectal lidocaine gel instillation. Cancer detection and complication rates were compared between the two groups. Univariate and multivariate binary logistic regression and multinomial logistic regression analyses were conducted to investigate the effects of sedation anesthesia with IV propofol on prostate cancer detection and complication rates. RESULTS: The cancer detection rate of patients in the sedation group was 34.0%, whereas it was 29.2% in the local group (P = 0.024). Multivariate logistic regression analysis regarding factors associated with cancer detection rate after TRUS-guided prostate biopsy in patients with prostate specific antigen (PSA) < 10 showed that IV propofol usage, age, PSA density and core length were significant factors. Multivariate logistic regression analysis regarding factors associated with complications (voiding dysfunction, bleeding and infection) showed that IV propofol usage, age and prostate size were significant factors for voiding dysfunction. CONCLUSION: Sedation anesthesia with IV propofol during TRUS-guided prostate biopsy was associated with a higher cancer detection rate than local anesthesia with intrarectal lidocaine gel instillation. Cancer detection rate could be an important factor to consider when selecting for the optimal anesthesia for TRUS-guided prostate biopsy.

Effects of an alpha-1d adrenoreceptor antagonist (naftopidil) on bladder dysfunction after radiotherapy in female rats.

PURPOSE: Storage-phase bladder dysfunction can develop after pelvic radiotherapy. As the alpha-1d adrenoreceptor (a1d-AR) is dominant in the human detrusor, we aimed to investigate the effect of an a1d-AR antagonist on bladder dysfunction after pelvic radiotherapy in a rat model. MATERIALS AND METHODS: Twenty-four female Wistar rats were used. Eight rats (14-15 weeks, 250-300 g) were randomized to three groups (normal reference group, radiation alone group and radiation plus naftopidil group). An 18-Gy dose of radiotherapy was applied to the radiation alone and radiation plus naftopidil groups. Naftopidil (20 mg/kg) was administered daily to the radiation plus naftopidil group. Four weeks after radiation, all rats underwent cystometry and were killed for reverse transcription polymerase chain reaction to detect mRNAs [a1d-AR, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF)], Western blot to detect proteins (a1d-AR, extracellular-signal-regulated kinase, BDNF and VEGF) and immunohistochemistry. RESULTS: Compared to the radiation alone group, (1) the decrease in the mRNA and protein expression of a1d-AR and VEGF was ameliorated, (2) the increase in the expression of BDNF mRNA and proteins such as extracellular-signal-regulated kinase and BDNF was suppressed, (3) submucosal thickness and vascularity on immunohistochemistry were improved, and (4) the baseline intravesical pressure and intercontraction interval in cystometry were ameliorated in the radiation plus naftopidil group. CONCLUSION: Administration of an a1d-AR antagonist could improve storage-phase bladder dysfunction after radiotherapy not only by upregulating a1d-AR, which might decrease bladder compliance, but also by enhancing vascularity, which might protect the urinary bladder from chronic ischemic inflammation.

Role of sex hormones in cervical changes in a cervical excision-related preterm delivery mouse model.

Progesterone and oestrogen play important roles during parturition; however, their roles in the uterine cervix during preterm labour and delivery are unknown. We evaluated the serum progesterone and oestrogen levels and changes in their receptors (PR and ER) in the cervix in a cervical excision-associated preterm delivery mouse model. Adult female C57BL/6 mice were divided into four groups: sham, cervical excision (Ex), lipopolysaccharide (LPS) and Ex + LPS. Mating was permitted at 3 weeks post-Ex. On gestation day 16, mice were administered LPS intrauterine (100 µg/100 µL/mouse) or physiological saline (100 µL) via laparotomy. Uterine cervices and blood were sampled immediately postpartum. As a result, epithelial PR and muscular ERα were down- and upregulated, respectively, in the proximal cervix in Ex + LPS group compared to in the sham group. These results indicate that unique sex hormone effects are exerted on the uterine cervix during cervical excision-associated spontaneous preterm labour and delivery.Impact statementWhat is already known on this subject? Preterm and term parturition require the withdrawal of progesterone and the activation of oestrogen in the uterine body and systemic levels. However, we have little understanding of the role of the sex hormones in the uterine cervix.What do the results of this study add? Increased ERα-to-PR expression ratio in the proximal cervix was associated with preterm labour and delivery. ERα expression in the smooth muscle layer of the proximal cervix was higher and PR expression in the proximal cervix epithelium was lower during preterm labour and delivery.What are the implications of these findings for clinical practice and/or further research? This study revealed the differences between the roles of sex hormones and their receptors in epithelial and muscle layers of proximal and distal cervices in preterm labour and delivery.

Critical causes in severe bleeding requiring angioembolization after percutaneous nephrolithotomy.

BACKGROUND: To identify the risk factors for severe bleeding requiring angioembolization among patients who received transfusions after PCNL, particularly those who underwent anatomically incorrect renal puncture. METHODS: A total of 53 patients, who received transfusions after PCNL and simultaneously had a postoperative CT scan performed between November 2009 and May 2019 at two teaching hospitals, were retrospectively reviewed. The patients were divided into two groups: those who underwent angioembolization and those who did not. Patient, stone and procedural factors were compared between the two groups. Puncture correctness was evaluated using postoperative CT scans. Puncture was defined as being a correct puncture if the fornix or papilla of the posterior calyx was punctured and the trajectory of the tract was within 20 degrees posterior to the frontal plane of the kidney (i.e., within Brödel's line). RESULTS: 21 patients underwent angioembolization after PCNL. Incorrect puncture was seen in 14/21 (66.7%) patients who underwent angioembolization after PCNL, whereas it was seen in 11/32 (34.4%) patients who did not undergo angioembolization (p = 0.021). On multivariable regression analysis, puncture correctness was found to be the only significant factor, with an OR of 3.818, 95% CI of 1.192-12.231 and p value of 0.024. CONCLUSIONS: Incorrect renal puncture was related to severe bleeding requiring angioembolization after PCNL. Our results emphasize the importance of the basic principle of renal puncture for PCNL.

Anterograde irrigation - assisted ureteroscopic lithotripsy in patients with percutaneous nephrostomy.

In complicated urinary tract infection with ureteral calculi, urinary diversion is inevitable. So, stenting or percutaneous drainage can be an option. In hemodynamically unstable patients, percutaneous drainage is superior to ureteral stenting (1). Once acute infection is controlled, definite treatment of the stone is necessary. According to a guideline, semirigid ureteroscopy is recommended for lower and mid - ureter stone and flexible ureteroscopy for upper ureter stone (2). Semi - rigid ureteroscopy can migrate stone to kidney, especially in upper ureter stone, lowering stone free rate (3). Not only flexible ureteroscopy creates additional costs but also is barely available in developing countries (4, 5). So, the authors would like to introduce anterograde irrigation - assisted ureteroscopic lithotripsy in patients with percutaneous nephrostomy. Retrograde irrigation was connected and flowed minimally enough to secure visual field. Once stone is noted, another saline irrigation, which is placed above 40 cm over the patient is connected to nephrostomy. Retrograde irrigation is disconnected from ureteroscope and the previous connected channel on ureteroscope is opened. Actual pressure detected by barometer from the opened channel of ureteroscope is usually about 30 cmH2O while anterograde irrigation is administered in maximal flow, which means fully opened anterograde irrigation is not hazardous to kidney. There was no complication in 17 patients submitted to this method. Video shows advantages of our practice: clear visual field; reduced risk of stone migration into kidney; induced spontaneous passage of fragments without using instrumentation; and decreased operation time. In short, most of surgeons, even unexperienced, can perform an excellent procedure with less time consuming using our method.

Protective effects of carbenoxolone, an 11ß-HSD1 inhibitor, against chemical induced dry eye syndrome.

Dry eye syndrome (DES) is a disorder of the eye due to tear deficiency or excessive evaporation that causes damage to the eye and is associated with discomfort and dryness. 11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) is an enzyme that converts inactive cortisone to active cortisol. Recently, 11ß-HSD1 has been expressed in human and rodent eyes and has been recognized as a target of glaucoma. In this study, the therapeutic effects and underlying mechanisms of topical carbenoxolone, an 11ß-HSD1 inhibitor, were investigated in benzalkonium chloride (BAC)-treated human conjunctival epithelial cells and a rat DES model. In the in vitro study, carbenoxolone dose-dependently inhibited cell death and 11ß-HSD1 activity in BAC-treated human conjunctival epithelial cells. For the in vivo study, carbenoxolone or a solvent was administered to the BAC-induced DES model twice daily. BAC-treated rat eyes showed significant increases in ocular surface damage, a reduction of tears, decrease corneal thickness, corneal basement membrane destruction, apoptosis in the conjunctival epithelium, and expression of pro-inflammatory cytokines (TNF-α and IL-6) and 11ß-HSD1. These effects of BAC were reversed by topical carbenoxolone treatment. These results demonstrate that carbenoxolone can prevent DES by inhibiting pro-inflammatory cytokine expression and cell death of the corneal and conjunctival epithelium via inhibition of both 11ß-HSD1 activity and expression in the eyes of BAC-treated rats. It is suggested that topical 11ß-HSD1 inhibitors may provide a new therapeutic window in the prevention and/or treatment of DES.

Anti-inflammatory effect of a selective 11ß-hydroxysteroid dehydrogenase type 1 inhibitor via the stimulation of heme oxygenase-1 in LPS-activated mice and J774.1 murine macrophages.

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) converts inactive cortisone to the active cortisol. 11ß-HSD1 may be involved in the resolution of inflammation. In the present study, we investigate the anti-inflammatory effects of 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), a selective 11ß-HSD1 inhibitor, in lipopolysaccharide (LPS)-activated C57BL/6J mice and macrophages. LPS increased 11ß-HSD1 activity and expression in macrophages, which was inhibited by KR-66344. In addition, KR-66344 increased survival rate in LPS treated C57BL/6J mice. HO-1 mRNA expression level was increased by KR-66344, and this effect was reversed by the HO competitive inhibitor, ZnPP, in macrophages. Moreover, ZnPP reversed the suppression of ROS formation and cell death induced by KR-66344. ZnPP also suppressed animal survival rate in LPS plus KR-66344 treated C57BL/6J mice. In the spleen of LPS-treated mice, KR-66344 prevented cell death via suppression of inflammation, followed by inhibition of ROS, iNOS and COX-2 expression. Furthermore, LPS increased NFκB-p65 and MAPK phosphorylation, and these effects were abolished by pretreatment with KR-66344. Taken together, KR-66344 protects against LPS-induced animal death and spleen injury by inhibition of inflammation via induction of HO-1 and inhibition of 11ß-HSD1 activity. Thus, we concluded that the selective 11ß-HSD1 inhibitor may provide a novel strategy in the prevention/treatment of inflammatory disorders in patients.

Acute bacterial prostatitis and abscess formation.

BACKGROUND: The purpose of this study was to identify risk factors for abscess formation in acute bacterial prostatitis, and to compare treatment outcomes between abscess group and non-abscess group. METHODS: This is a multicenter, retrospective cohort study. All patients suspected of having an acute prostatic infection underwent computed tomography or transrectal ultrasonography to discriminate acute prostatic abscesses from acute prostatitis without abscess formation. RESULTS: A total of 31 prostate abscesses were reviewed among 142 patients with acute prostatitis. Univariate analysis revealed that symptom duration, diabetes mellitus and voiding disturbance were predisposing factors for abscess formation in acute prostatitis. However, diabetes mellitus was not related to prostate abscess in multivariate analysis. Patients with abscesses <20 mm in size did not undergo surgery and were cured without any complications. In contrast, patients with abscesses >20 mm who underwent transurethral resection had a shorter duration of antibiotic treatment than did those who did not have surgery. Regardless of surgical treatment, both the length of hospital stay and antibiotic treatment were longer in patients with prostatic abscesses than they were in those without abscesses. However, the incidence of septic shock was not different between the two groups. A wide spectrum of microorganisms was responsible for prostate abscesses. In contrast, Escherichia coli was the predominant organism responsible for acute prostatitis without abscess. CONCLUSION: Imaging studies should be considered when patients with acute prostatitis have delayed treatment and signs of voiding disturbance. Early diagnosis is beneficial because prostatic abscesses require prolonged treatment protocols, or even require surgical drainage. Surgical drainage procedures such as transurethral resection of the prostate were not necessary in all patients with prostate abscesses. However, surgical intervention may have potential merits that reduce the antibiotic exposure period and enhance voiding function in patients with prostatic abscess.

Identification of a novel 11ß-HSD1 inhibitor from a high-throughput screen of natural product extracts.

Selective inhibitors of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) have considerable potential as a treatment for metabolic syndrome including type 2 diabetes mellitus and obesity. To identify 11ß-HSD1 inhibitors, we conducted high-throughput screening (HTS) of active natural product extracts from the Korea Chemical Bank, including Tanshinone I, Tanshinone IIA, and flavanone derivatives, and 2- and 3-phenyl-4H-chromen-4-one. Then Tanshinone IIA and its derivatives were targeted for the development of a lead compound according to the HTS results. However, the mechanism for anti-adipogenic effect through 11ß-HSD1 enzyme inhibition by Tanshinone IIA is not clear. Tanshinone IIA (2a) concentration-dependently inhibited 11ß-HSD1 activity in human and mouse 11ß-HSD1 overexpressed cells and 3T3-L1 adipocytes. Tanshinone IIA (2a) also inhibited 11ß-HSD1 enzyme activities in murine liver and fats. Furthermore, Tanshinone IIA (2a)-suppressed adipocyte differentiation of cortisone-induced adipogenesis in 3T3-L1 cells was associated with the suppression of the cortisone-induced adipogenesis-specific markers mRNA and protein expression. In 3T3-L1 preadipocytes, Tanshinone IIA (2a)-inhibited cortisone induced reactive oxygen species formation in a concentration-dependent manner. Thus, these results support the therapeutic potential of Tanshinone IIA (2a) as a 11ß-HSD1 inhibitor in metabolic syndrome patients.

CONSUMERS' INTENTION TO ATTEND SOCCER EVENTS: APPLICATION AND EXTENSION OF THE THEORY OF PLANNED BEHAVIOR.

The purpose of this study was to identify important factors of consumers' intention to attend professional soccer events among Saudi Arabian soccer fans. To explore the decision-making process of this relatively understudied population, the theory of planned behavior was used as theoretical background. Particularly, this study measured the effect of attitude, subjective norm, perceived behavioral control (time and money), and game importance on intention to attend, and examined the moderating role of commitment. Structural equation modeling (SEM) using 231 Saudi university students (M = 21.9 yr., SD = 1.21) indicate that attitude and game importance were significantly related to attendance intention. The effect of subjective norms was significant only for the low commitment group and game importance was more important for the low than the high commitment group.

Water Vapor Therapy and Zonal Anatomy of the Prostate.

Water vapor therapy using Rezum has been recently introduced as a minimally invasive surgery for benign prostatic hyperplasia and is being increasingly performed. However, there is a lack of real-time images showing this practice and how convective water vapor acts in the prostate gland. In real-time ultrasonography, convective water vapor rapidly spreads throughout the ipsilateral transitional zone and is mostly limited within the transitional zone. For educational purposes, we would like to present a case to help readers understand water vapor therapy by visualizing convective water vapor using real-time ultrasound.

Pirfenidone improves voiding function by suppressing bladder fibrosis in underactive bladder rats.

Underactive bladder (UAB), characterized by a complex set of symptoms with few treatment options, can significantly reduce the quality of life of affected people. UAB is characterized by hyperplasia and fibrosis of the bladder wall as well as decreased bladder compliance. Pirfenidone is a powerful anti-fibrotic agent that inhibits the progression of fibrosis in people with idiopathic pulmonary fibrosis. In the current study, we evaluated the efficacy of pirfenidone in the treatment of bladder fibrosis in a UAB rat model. UAB was induced by crushing damage to nerve bundles in the major pelvic ganglion. Forty-two days after surgery, 1 mL distilled water containing pirfenidone (100, 300, or 500 mg/kg) was orally administered once every 2 days for a total of 10 times for 20 days to the rats in the pirfenidone-treated groups. Crushing damage to the nerve bundles caused voiding dysfunction, resulting in increased bladder weight and the level of fibrous related factors in the bladder, leading to UAB symptoms. Pirfenidone treatment improved urinary function, increased bladder weight and suppressed the expression of fibrosis factors. The results of this experiment suggest that pirfenidone can be used to ameliorate difficult-to-treat urological conditions such as bladder fibrosis. Therefore, pirfenidone treatment can be considered an option to improve voiding function in patient with incurable UAB.

Application of Bipolar Cauterization During Standard Percutaneous Nephrolithotomy.

Introduction: We aimed to evaluate the efficacy of bipolar cauterization for tract site bleeding during standard percutaneous nephrolithotomy (PCNL). Methods and Materials: We defined tract site bleeding as when the visual field across the parenchymal tract starts to bleed while the sheath of a balloon dilator is being withdrawn just before the operation is completed. Among 181 patients, 90 patients showed no significant bleeding, and 91 patients required further procedures to resolve tract site bleeding. In cases of unresolved tract site bleeding, either nephrostomy placement (n = 60) or cauterization (n = 31) was performed. The outcomes of three groups (no procedure group, nephrostomy group and cauterization group) were compared. Results: The median decrease in hemoglobin at 2-hour intervals postoperatively was -1.75, -1.0, and -0.2 in the nephrostomy, cauterization, and no procedure groups, respectively (P < .001). There were 25 patients (41.7%) who received transfusions in the nephrostomy group, whereas only 1 patient (3.2%) received a transfusion in the cauterization group (P < .001). Conclusion: The bipolar cauterization of bleeding points at the end of PCNL could efficiently decrease tract site bleeding and reduce the need for transfusion. Clinical Research Information Service (https://cris.nih.go.kr/cris; No. KCT0008303).

Symmetry Breaking of Human Pluripotent Stem Cells (hPSCs) in Micropattern Generates a Polarized Spinal Cord-Like Organoid (pSCO) with Dorsoventral Organization.

Axis formation and related spatial patterning are initiated by symmetry breaking during development. A geometrically confined culture of human pluripotent stem cells (hPSCs) mimics symmetry breaking and cell patterning. Using this, polarized spinal cord organoids (pSCOs) with a self-organized dorsoventral (DV) organization are generated. The application of caudalization signals promoted regionalized cell differentiation along the radial axis and protrusion morphogenesis in confined hPSC colonies. These detached colonies grew into extended spinal cord-like organoids, which established self-ordered DV patterning along the long axis through the spontaneous expression of polarized DV patterning morphogens. The proportions of dorsal/ventral domains in the pSCOs can be controlled by the changes in the initial size of micropatterns, which altered the ratio of center-edge cells in 2D. In mature pSCOs, highly synchronized neural activity is separately detected in the dorsal and ventral side, indicating functional as well as structural patterning established in the organoids. This study provides a simple and precisely controllable method to generate spatially ordered organoids for the understanding of the biological principles of cell patterning and axis formation during neural development.

Analysis of population structure among Korean and Japanese Legionella pneumophila isolates using hsp60 sequences.

The population structure of Korean (150 strains) and Japanese (92 strains) Legionella pneumophila isolates along with 18 reference strains were investigated using hsp60 sequence (1647 bp) analysis. Twelve clonal subgroups (hsP-I to hsP-X and hsF-I and hsF-II) were designated on the hsp60 tree, inferred from representative sequences using the neighbor-joining method. Some of the isolates showed unique subgroups depending on the source of isolates, including hsP-I, hsF-I, and hsF-II from cooling tower water, and subgroups hsP-VIII and hsP-X from circulating hot water bath. These subgroups may be useful for epidemiological studies to chase or specify sources of infection in Korea and Japan.

Effect of a three-dimensional (3D) printed kidney model on patient understanding of the percutaneous nephrolithotomy procedure: a preliminary study.

Three-dimensional (3D) printed anatomical models can provide cognitive anatomical information. We aimed to study the effect of a 3D printed kidney model on patient understanding of kidney anatomy and the percutaneous nephrolithotomy (PCNL) procedure as well as the overall patient satisfaction with the model. Seven patients who underwent PCNL were enrolled in the study. Personalized 3D printed kidney models were constructed based on the patients' computed tomography images. Patients completed two questionnaires regarding their understanding and satisfaction with the use of the 3D printed kidney model before and after using the model during informed consent. The mean age of the study population was 58.0 years. Comparison of patient understanding and satisfaction between the two questionnaires showed a general trend toward better understanding and improved satisfaction with use of 3D printed kidney models. Statistically significant results were seen for understanding of kidney anatomy, stone size, procedure, and satisfaction (p values 0.046, 0.025, 0.046, and 0.046, respectively). Five of the seven patients (71.4%) answered that the model was very useful. However, none of the patients answered that the cost was appropriate. In the current study, patients showed improved understanding of the kidney anatomy and the PCNL procedure and higher satisfaction with using the 3D printed kidney model during informed consent. With further studies using larger patient numbers and decreased production cost, using 3D printed kidney models has the potential to be a useful adjunct for patient understanding during PCNL.

Inhibitory effect of leptin on rosiglitazone-induced differentiation of primary adipocytes prepared from TallyHO/Jng mice.

The effects of leptin on rosiglitazone-induced adipocyte differentiation were investigated in the primary adipocytes prepared from subcutaneous fat of TallyHO/Jng (TallyHO) mouse, a recently developed model animal for type 2 diabetes mellitus (T2DM). The treatment of leptin inhibited the rosiglitazone-induced adipocyte differentiation with a decreased expression of peroxisome proliferator-activated receptor γ (PPARγ) a key adipogenic transcription factor, both in mRNA and protein levels. Leptin (10 nM) was sufficient to inhibit the adipocyte differentiation, which seemed to come from increased expression of leptin receptor genes in the fat of TallyHO mice. The inhibition of adipogenesis by leptin was restored by the treatment of inhibitors for extracellular-signal-regulated kinase (ERK) (PD98059) and signal transducer and activator of transcription-1 (STAT1) (fludarabine). Furthermore, in vivo intraperitoneal administration of PD98059 and fludarabine increased the PPARγ expression in the subcutaneous fat of TallyHO mice. These data suggest that leptin could inhibit the PPARγ expression and adipocyte differentiation in its physiological concentration in TallyHO mice.