Modulation of cue-induced firing of ventral tegmental area dopamine neurons by leptin and ghrelin.

BACKGROUND/OBJECTIVES: The rewarding value of palatable foods contributes to overconsumption, even in satiated subjects. Midbrain dopaminergic activity in response to reward-predicting environmental stimuli drives reward-seeking and motivated behavior for food rewards. This mesolimbic dopamine (DA) system is sensitive to changes in energy balance, yet it has thus far not been established whether reward signaling of DA neurons in vivo is under control of hormones that signal appetite and energy balance such as ghrelin and leptin. SUBJECTS/METHODS: We trained rats (n=11) on an operant task in which they could earn two different food rewards. We then implanted recording electrodes in the ventral tegmental area (VTA), and recorded from DA neurons during behavior. Subsequently, we assessed the effects of mild food restriction and pretreatment with the adipose tissue-derived anorexigenic hormone leptin or the orexigenic hormone ghrelin on VTA DA reward signaling. RESULTS: Animals showed an increase in performance following mild food restriction (P=0.002). Importantly, food-cue induced DA firing increased when animals were food restricted (P=0.02), but was significantly attenuated after leptin pretreatment (P=0.00). While ghrelin did affect baseline DA activity (P=0.025), it did not affect cue-induced firing (P⩾0.353). CONCLUSIONS: Metabolic signals, such as leptin, affect food seeking, a process that is dependent on the formation of cue-reward outcomes and involves midbrain DA signaling. These data show that food restriction engages the encoding of food cues by VTA DA neurons at a millisecond level and leptin suppresses this activity. This suggests that leptin is a key in linking metabolic information to reward signaling.

Androgenetic alopecia is associated with increased arterial stiffness in asymptomatic young adults.

BACKGROUND: Association of androgenetic alopecia (AGA) with increased incidence of hypertension, a strong risk factor for coronary artery disease, has been suggested. However, there are no data on arterial stiffness measures of asymptomatic young adults with AGA. OBJECTIVE: In this study, we aimed to investigate the association of the AGA with arterial stiffness assessed by cardio-ankle vascular index (CAVI), in asymptomatic young men. METHODS: A total of 162 asymptomatic men aged between 18 and 45 years were consecutively enrolled to the study. Subjects were considered to have AGA if they have ≥3 grade vertex alopecia according to Hamilton-Norwood scale. Arterial stiffness was assessed by CAVI and defined as abnormal if CAVI is ≥8. RESULTS: Frequency of abnormal CAVI was higher in patients with AGA (29.3% vs. 10.0%, P = 0.003). Subjects with AGA had higher mean CAVI than subjects without AGA (7.56 ± 0.93 vs. 7.15 ± 0.79, P = 0.004). Binary logistic regression analysis demonstrated that presence of AGA (OR, 5.6; 95% CI, 1.7-20.0, P = 0.006), age (OR, 1.1; 95% CI, 1.0-1.2, P = 0.03) and diastolic blood pressure (OR, 1.1; 95% CI, 1.0-1.3, P = 0.005) were independently associated with abnormal CAVI. CONCLUSION: We concluded that, AGA might be an indicator of arterial stiffness in asymptomatic young adults.

Link between aortic valve sclerosis and myocardial no-reflow in ST-segment elevation myocardial infarction.

OBJECTIVE: The"no-reflow" phenomenon is associated with a worse prognosis at follow-up for patients with acute ST-segment elevation myocardial infarction (STEMI). Predicting and preventing no-reflow is therefore a crucial step in improving the prognosis of STEMI patients. The purpose of this study was to investigate the association between aortic valve sclerosis (AVS) and myocardial no-reflow in patients with STEMI. PATIENTS AND METHODS: Patients with a first-time diagnosis of STEMI were enrolled consecutively. No-reflow was defined as a final TIMI 3 flow with a myocardial blush of grade < 2, temporary epicardial coronary no-reflow, and distal coronary occlusion. AVS was defined by echocardiography as thickening and calcification of the normal trileaflet aortic valve without obstruction to the left ventricular outflow. RESULTS: No-reflow developed in 41 patients. In univariate analysis, age, male gender, smoking, culprit lesion Syntax score (SX score), and hypertension were significantly associated with no-reflow. Multivariate binary logistic regression analyses demonstrated age [95 % confidence interval (CI), 1.024-1.096; p=0.001), AVS (95 % CI, 1.002-1.100; p=0.039], culprit lesion SX score (95 % CI, 1.08-1.021 p=0.008), and symptom-to-balloon time (95 % CI, 1.020-1.097; p=0.002) as independent determinants of myocardial no-reflow. CONCLUSION: AVS was significantly and independently associated with myocardial no-reflow in STEMI patients.

Aortic valve sclerosis in acute coronary syndrome patients : potential value in predicting coronary artery lesion complexity.

OBJECTIVE: The purpose of the present study was to investigate the relation between aortic valve sclerosis (AVS) and coronary artery lesion complexity as assessed using the SYNTAX score (SxScore) in acute coronary syndrome (ACS) patients. PATIENTS AND METHODS: A total of 164 patients with a first time diagnosis of acute coronary syndrome were consecutively enrolled. AVS was defined by echocardiography as thickening and calcification of the normal trileaflet aortic valve without obstruction to the left ventricular outflow. The SxScore was calculated using dedicated computer software. RESULTS: There were significantly higher SxScores in subjects with AVS than those without AVS (18 ± 6 vs 12 ± 5, p = 0.02). In the univariate analysis, age (p = 0.03) and presence of AVS (p = 0.007) were significantly associated with higher SxScores. Logistic regression analysis demonstrated AVS [95 % confidence interval (CI) 0.17-0.86, p = 0.017] and age (95 % CI 1.01-1.21, p = 0.028) as independent determinants of higher SxScores. CONCLUSION: Aortic valve sclerosis was significantly and independently associated with a high SxScore in acute coronary syndrome patients.

Does tension-free vaginal tape and tension-free vaginal tape-obturator affect urodynamics? Comparison of the two techniques.

AIM: To evaluate the effects of tension-free vaginal tape (TVT) and tension-free vaginal tape-obturator (TVT-O) operations on urodynamics and subjective and objective outcomes. MATERIALS AND METHODS: Thirty-six patients with stress or mixed urinary incontinence underwent TVT or TVT-O. Bristol Female Lower Urinary Tract Symptoms (BFLUTS) Questionnaire-Scored Form, one-hour pad test, Q-tip test, perineometer, and urodynamics were performed before and after the operations. Blaivas-nomogram was used for assessment of postoperative voiding difficulty. RESULTS: Nineteen patients underwent TVT-O and 17 patients underwent TVT. Mean follow-up was 18.4 +/- 6.8 months. There was no difference between two groups regarding demographic variables, degree of prolapse, type of incontinence, perineometer, Q-tip test, pad test, and urodynamics. There was a significant increase in the maximum urethral closure pressure (MUCP) and residual volume in TVT-O group. According to Blaivas-nomogram, five patients had mild, one had medium obstruction in the TVT-O group, whereas one had mild and three had medium obstruction in TVT group. Two bladder perforations occurred during TVT. One patient developed groin pain after TVT-O. CONCLUSIONS: TVT-O may lead to an increase in MUCP and residual urine volume. TVT-O is as efficient as TVT and leads to milder obstruction when compared to TVT.

Mean platelet volume on admission is associated with further left ventricular functions in primary PTCA patients.

AIM: In ST elevation myocardial infarction (STEMI) patients, mean platelet volume (MPV) is associated with infarct related artery patency both before and after reperfusion. In anterior STEMI patients successfully treated with primary percutaneous coronary intervention (PCI), the relationship between left ventricular (LV) function and MPV on admission is unknown. METHODS: 97 anterior STEMI patients successfully revascularizated with PCI between January 2010 and February 2011 are included. MPV on admission is recorded. All patients underwent transthoracic echocardiography within 3 days or before discharge. Patients were divided into two groups according to left ventricular ejection fraction (LVEF), as systolic dysfunction (LVEF < 50%, 1st group) and normal systolic functions (LVEF > 50%, 2nd group). The 1st group included 61 (47 males) patients and the 2nd group included 36 (35 males) patients. RESULTS: MPV was; 9.5+/-1.1 femtoliter (fL) in the 1st and 8.8+/-0.8 fL in the second group. The difference between the groups was significant (p = 0.001). There was a significant difference in the Troponin I levels and white blood cell (WBC) counts on admission between two groups (30+/-29 vs 12.2+/-15.1 ng/mL, p = 0.001 and 12.3+/-3.8 vs 10.6+/-3.4 counts ×109/L, p = 0.027, respectively). CONCLUSIONS: In anterior STEMI patients treated with percutaneous coronary intervention, increased MPV on admission is associated with impairment in left ventricular systolic function.

Clinical pregnancy rates in an IVF program. Use of the flare-up protocol after failure with long regimens of GnRH-a.

OBJECTIVE: To examine the efficacy of flare-up protocols in patients who failed to respond to a long protocol using gonadotropin-releasing hormone agonist (GnRH-a). STUDY DESIGN: In this retrospective study, a total of 144 patients who underwent an in vitro fertilization/embryo transfer cycle with the flare-up protocol were analyzed. Of these, 111 patients (group I) had not responded well to ovulation induction with long-term down-regulation with GnRH-a (long protocol), and 33 (group II) had responded to ovulation induction with at least four follicles but failed to conceive after embryo transfer. The average age of the patients were 37.3 +/- 3.9 years (range, 28-43) and 36.5 +/- 3.7 (range, 24-44), respectively. All patients underwent a flare-up protocol with GnRH-a (leuprolide acetate, 0.5 mg/d) on day 2 and at least 6 ampules of gonadotropins on day 3 within 6 months following failure with the long protocol. Unresponsiveness was defined as having fewer than three developing follicles on day 7, with an estradiol level < 200 pg/mL. Patients with a cycle day 2 follicle stimulating hormone (FSH) level > 15 mIU/mL before initiating GnRH-a were not included in the flare-up protocol. The average day 2 FSH levels of the patients on the flare-up protocol cycles were 9.1 +/- 3.0 in group I and 7.1 +/- 2.0 in group II. RESULTS: In group I, 44 of 111 (39.6%) patients did not respond to the flare-up protocol even with an increased dose of gonadotropins. In 67 patients, an average of 7.2 +/- 2.3 oocytes were obtained. Embryo transfer was performed on 64 patients with an average of 3.2 +/- 0.6 embryos. Fertilization did not occur in three patients. Eleven women conceived, eight of them miscarried, and three delivered. The pregnancy rate per cycle initiated was 9.9% (11/111) and live birth rate per cycle initiated, 2.5% (3/111). In group II, 3 of 33 patients were cancelled. The reasons were inadequate ovarian response, risk of hyperstimulation and absence of oocytes after aspiration. In 28 patients the average number of oocytes obtained was 6.9 +/- 3.9, and the average number of embryos replaced was 2.7 +/- 1.0. Six patients conceived, and all miscarried. The pregnancy rate per cycle initiated was 6/33 (18.1%), and no live births were achieved. CONCLUSION: Although the flare-up protocol after an unsuccessful luteal phase long protocol increases the pregnancy rate per cycle slightly, the live birth rate is not improved in poor responders.

Functional outcome in stroke patients with atrial fibrillation.

OBJECTIVES: To identify the prevalence of atrial fibrillation (AF) in a sample of stroke patients and to evaluate the impact of AF on patient clinical characteristics and functional outcome. DESIGN: A retrospective case-comparison study. SETTING: University-affiliated rehabilitation centers. PARTICIPANTS: One hundred ninety-six of 231 consecutive stroke patients admitted to inpatient rehabilitation units were evaluated during the rehabilitation period. MAIN OUTCOME MEASURES: Characteristics of cerebral lesions, patient demographic features, disease duration, length of hospital stay (LOS), risk factors for stroke, and functional status at admission and at discharge were assessed and compared in patients with and without AF. Functional Independence Measure (FIM) and Adapted Patient Evaluation Conference System (APECS) were used to evaluate functional status. RESULTS: AF was diagnosed in 41 (20.1%) patients. Patients who had AF were more likely to have ischemic cerebral lesions. There were no significant differences between the AF and non-AF groups with regard to mean age, LOS, and disease duration. Ischemic and valvular heart disease were more common in patients with AF. Based on FIM and APECS scores, both initial and discharge disability were more severe in patients with AF. In a multivariate model, AF was a negative prognostic factor for functional outcome in stroke patients. CONCLUSION: AF is not only associated with increased risk of stroke, but also with markedly greater disability in stroke patients. Factors such as size and type of cerebral lesions, stroke severity, comorbid conditions, and impact of AF on systemic and cerebral circulation can influence stroke recovery.