Serum free fatty acid levels in PCOS patients treated with glucophage, magnesium oxide and spironolactone.

To assess the effect of glucophage, magnesium oxide and spironolactone in altering free fatty acids (FFAs), 36 PCOS women were randomly divided into three groups. Group 1 (n = 14) was treated with 500 mg glucophage po bid, group 2 (n = 10) was treated with 400 mg magnesium oxide po bid and group 3 (n = 12) was treated with 50 mg spironolactone po bid for 12 weeks. A glucose tolerance test with 75 g glucose load was performed before and after treatment, collecting blood at 0, 1 and 2 h for insulin, glucose, FFA and aldosterone. Amount of FFA before and after treatment were compared by repeated measure ANOVA and represented as area under the curve. FFA levels before treatment were 0.83 ± 0.23, 0.77 ± 0.15 and 0.85 ± 0.28 and after treatment were 0.77 ± 0.48, 0.71 ± 0.18 and 0.66 ± 0.25 for glucophage, magnesium oxide and spironolactone-treated patients, respectively. The FFA levels were unchanged in the groups treated with glucophage and magnesium oxide but were significantly (p < 0.03) decreased in the group treated with spironolactone. Since FFAs are known to be involved in the development of insulin resistance, these results suggest that spironolactone may be useful for lowering insulin resistance in PCOS patients.

Localized transmeningeal muscimol prevents neocortical seizures in rats and nonhuman primates: therapeutic implications.

PURPOSE: To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)-induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity. METHODS: Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or muscimol (0.25-12.5 mm) was delivered locally as a "pretreatment," followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and muscimol (2.5 mm) exposures were measured. In a last group of four rats, muscimol (0.8-2.5 mm) was delivered epidurally during the ongoing, Ach-induced EEG seizure. RESULTS: In contrast to ACSF pretreatments, epidural muscimol pretreatment in rats completely prevented the seizures at and above 2.5 mm. In the monkeys, subarachnoid muscimol pretreatments at 2.5 mm completely prevented the focal-seizure-inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 mm epidural muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1-3 min. CONCLUSIONS: The results of this study suggest that muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy.

Evaluation of sleep apnea in a sample of black patients.

OBJECTIVES: Few minority patients with sleep apnea have been evaluated or treated. This study ascertained adherence rate to referrals for sleep apnea evaluation by primary care physicians in a community-based sample of black patients; it also examined baseline characteristics likely to influence adherence rates. METHODS: A retrospective chart audit was conducted at a hospital-based sleep clinic. Scrutiny was limited to male and female patients between the ages of 20 and 80 years. Data obtained for this analysis included baseline characteristics from a detailed sleep history and/or screening questionnaires and polysomnographic parameters. RESULTS: Of the 421 patients referred by their private care physicians, 38% (n=160) adhered to the recommendation for a sleep consultation, but all who showed up for their appointment underwent polysomnographic studies. Logistic regression analyses showed that obesity and daytime sleepiness were the most important factors predicting adherence, with multivariate-adjusted odds ratios of 2.69 [95% CI: 1.54-4.71, p < 0.001] and 6.98 [95% CI: 3.86-12.64, p < 0.001], respectively. Of the patients who underwent a polysomnographic sleep evaluation, 91% received a sleep apnea diagnosis and were treated. CONCLUSIONS: Black patients may be underutilizing available sleep services, but direct comparisons with other ethnic groups could not be made because of insufficient archival data. While the present study does not identify specific barriers to accessing services for sleep problems, it indicates that blacks who are obese and/or are experiencing daytime sleepiness are likely to adhere to recommendations of their physician. Targeted culturally congruent educational interventions to increase awareness of sleep apnea in black communities might help to increase adherence rate.

Symptoms of obstructive sleep apnea in a Caribbean sample.

Obstructive sleep apnea (OSA) is a prevalent sleep disorder that disproportionately affects blacks. While clinical and epidemiologic data indicate intraethnic differences in several medical diseases, little is known about whether OSA symptoms differ within the black ethnic group. We estimated the rate of OSA symptoms in a community-based sample of Caribbean-born black men and women. We also ascertained which sociodemographic and/or medical factors were associated with OSA risk. A total of 554 patients (mean age = 48.17 +/- 16.75 years) participated in the study; 55% were women. Data were collected in four primary-care clinics in Brooklyn, NY. A health educator explained the purpose of the study to interested patients and assisted consenting participants in completing questionnaires, which required 15 min to complete. Participants reporting habitual snoring, excessive daytime sleepiness, and sleep fragmentation were considered at high OSA risk. The rate of OSA symptoms was: snoring (45%), excessive daytime sleepiness (33%), and difficulty maintaining sleep (34%). Many reported falling asleep while watching television (47%) or while driving (14%). Based on logistic regression analysis, a history of heart disease was the most important predictor of the likelihood of expressing OSA symptoms, with a corresponding multivariate-adjusted odds ratio of 11 (95% confidence interval = 3.03-40.63). Findings suggest the need to investigate whether Caribbean-born blacks are at greater risk for developing OSA than African Americans and whites. Caribbean-born blacks with a history of heart disease should be a prime target for interventions that promote adequate screening and timely OSA diagnosis.

Perisaccadic parietal and occipital gamma power in light and in complete darkness.

Our objective was to determine perisaccadic gamma range oscillations in the EEG during voluntary saccades in humans. We evaluated occipital perisaccadic gamma activity both in the presence and absence of visual input, when the observer was blindfolded. We quantified gamma power in the time periods before, during, and after horizontal saccades. The corresponding EEG was evaluated for individual saccades and the wavelet transformed EEG averaged for each time window, without averaging the EEG first. We found that, in both dark and light, parietal and occipital gamma power increased during the saccade and peaked prior to reaching new fixation. We show that this is not the result of muscle activity and not the result of visual input during saccades. Saccade direction affects the laterality of gamma power over posterior electrodes. Gamma power recorded over the posterior scalp increases during a saccade. The phasic modulation of gamma by saccades in darkness--when occipital activity is decoupled from visual input--provides electrophysiological evidence that voluntary saccades affect ongoing EEG. We suggest that saccade-phasic gamma modulation may contribute to short-term plasticity required to realign the visual space to the intended fixation point of a saccade and provides a mechanism for neuronal assembly formation prior to achieving the intended saccadic goal. The wavelet-transformed perisaccadic EEG could provide an electrophysiological tool applicable in humans for the purpose of fine analysis and potential separation of stages of 'planning' and 'action'.

Sleep duration among black and white Americans: results of the National Health Interview Survey.

INTRODUCTION: Epidemiologic studies have shown the importance of habitual sleep duration as an index of health and mortality risks. However, little has been done to ascertain ethnic differences in sleep duration in a national sample. This study compares sleep duration in a sample of black and white participants in the National Health Interview Survey (NHIS). METHOD: Data were collected from 29,818 Americans (age range 18-85 years) who participated in the 2005 NHIS. The NHIS is a cross-sectional household interview survey that uses a multistage area probability design, thus permitting representative sampling of U.S. households. During face-to-face interviews conducted by trained interviewers from the U.S. Census Bureau, respondents provided demographic data and information about physician-diagnosed chronic conditions, estimated habitual sleep duration and functional capacity, and rated their mood. RESULTS: Fisher's exact test results indicated that blacks were less likely than whites to report sleeping 7 hours (23% vs. 30%; chi2 = 94, p < 0.0001). Blacks were more likely to experience both short sleep (< or = 5 hours) (12% vs. 8%, chi2 = 44, p < 0.0001) and long sleep (> or = 9 hours) (11% vs. 9%, chi2 = 23, p < 0.0001). Logistic regression analysis, adjusting for differences in sociodemographic factors, depression, functional capacity and medical illnesses, demonstrated that black ethnicity was a significant predictor of extreme sleep duration (Wald = 46, p < 0.0001; OR = 1.35, 95% CI: 1.24-1.47). DISCUSSION: Independent of several sociodemographic and medical factors, blacks had more prevalent short and long sleep durations, suggesting greater variation in habitual sleep time. Therefore, blacks might be at increased risks of developing medical conditions associated with short and long sleep.

Vascular compliance in women with polycystic ovary syndrome and healthy women.

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women of reproductive age, has been associated with the cardiometabolic syndrome and increased risk for cardiovascular diseases. Large (C1) and small (C2) vessel compliance and fasting lipids were measured in 45 healthy women and 36 women with PCOS. There were no differences in vacular compliance (C1, C2) between the 2 groups. Systolic blood pressure (116.8 vs 124.3 mm Hg; P=.01), mean arterial pressure (82.5 vs 87 mm Hg; P=.03), and low-density lipoprotein cholesterol (98.1 vs 119 mg/dL; P=.001) were significantly higher in the PCOS group. This difference was not significant after adjusting for age and body mass index. High-density lipoprotein levels in subjects with PCOS were significantly lower than in healthy women (60.2 vs 48.9 mg/dL, P=.02) even after adjusting for age and body mass index. The study indicates that obesity and low high-density lipoprotein are the major contributing factors to cardiovascular changes in PCOS.

Transmeningeal delivery of GABA to control neocortical seizures in rats.

Transmeningeal drug delivery, using an implanted hybrid neuroprosthesis, has been proposed as a novel therapy for intractable focal epilepsy. As part of a systematic effort to identify the optimal compounds and protocols for such a therapy, this study aimed to determine whether transmeningeal gamma-aminobutyric acid (GABA) delivery can terminate and/or prevent neocortical seizures in rats. Rats were chronically implanted with an epidural cup and an adjacent EEG electrode in the right parietal cortex. While the rat was behaving freely, a seizure-inducing concentration of acetylcholine (Ach) was applied into the cup. In a seizure termination study, either artificial cerebrospinal fluid (ACSF) or GABA (0.25, 2.5, 25 or 50mM) was delivered into the exposed neocortical area during an ongoing seizure. In a seizure prevention study, either ACSF or 50mM GABA was delivered into the epidural cup before the application of Ach. Epidural delivery of 50mM GABA completely terminated ongoing Ach-induced EEG seizures and convulsions within 17-437s after its delivery. ACSF and lower concentrations of GABA did not produce this effect, but 25mM GABA reduced seizure severity. However, the used GABA concentration could not prevent the development, or affect the severity, of Ach-induced EEG seizures and convulsions. This study indicates that transmeningeal GABA delivery can be used for terminating neocortical seizures, but to achieve seizure prevention via this route either a more efficient GABA delivery method needs to be developed or other neurotransmitters/pharmaceuticals should be employed for this purpose.

Sexually dimorphic recruitment of spinal opioid analgesic pathways by the spinal application of morphine.

Current evidence for sex-based nociception and antinociception, largely confined to behavioral measures of pain sensitivity, chronic pain syndromes, and analgesic efficacy, provides little mechanistic insights into biological substrates causally associated with sexual dimorphic pain experience. Spinal cord has been shown to be a central nervous system region in which regulation of opioid antinociceptive substrates manifest sexual dimorphism. This site was therefore chosen to explore whether or not differential mechanisms underlie comparable spinal opioid antinociception in male and female rodents. Intrathecal (i.t.) application of morphine to male and female rats produces a thermal antinociception equivalent in magnitude and temporal profile. Nevertheless, it results from the sex-based differential recruitment of spinal analgesic components. As expected, the spinal micro-opioid receptor is critical for i.t. morphine antinociception in both sexes. However, in females, but not males, activation by i.t. morphine of spinal kappa-opioid receptors is a prerequisite for spinal morphine antinociception. Furthermore, in females, but not males, i.t. application of antidynorphin antibodies substantially attenuates the antinociception produced by i.t. morphine. This indicates that the antinociception that results from the i.t. application of morphine in females requires the functional recruitment of spinal dynorphin. Female-specific recruitment by i.t. morphine of a spinal dynorphin/kappa-opioid receptor pathway results from organizational consequences of ovarian sex steroids and not the absence of testicular hormones. These observations suggest that sexual dimorphic pain and analgesic mechanisms might be far more pervasive than commonly thought and underscore the imperative for including female as well as male subjects in all studies of pain and antinociception.

Alcohol consumption and blood pressure in the adult US population: assessment of gender-related effects.

OBJECTIVE: Our objective was to assess the gender-related effects of alcohol consumption on blood pressure (BP) in a representative sample of the adult US population. METHODS: We examined data from the National Health and Nutrition Examination Survey 1999-2000. The effects of various risk factors for hypertension on BP were examined with analysis of covariance statistics. RESULTS: Of the 5448 adults over 20 years of age, 2650 (48.7%) reported the intake of one or more drinks per day over the past year. In this population, the mean +/- SEM age was 46.9 +/- 0.34 years, the body mass index was 24.8 kg/m, 1257 (47.4%) were women, systolic BP was 124.3 +/- 0.44 mmHg and diastolic BP was 72.7 +/- 0.27 mmHg. Hypertension was reported in 21.1%, diabetes in 5.1% and cigarette smoking in 39.7%. A significant effect on systolic BP was shown with age (P < 0.01), body mass index (P < 0.01), race (P = 0.01), gender (P < 0.01) and diabetes (P < 0.01). The interaction with gender and alcohol drinking level was significant (P = 0.02). Post-hoc analysis localized the source of this effect. There was a significant increase in systolic BP between one and three and between one and four, but not between one and two, drinks per day in men. This effect was not observed in women. CONCLUSION: Consistent with previous reports, our study suggests that alcohol intake up to two drinks per day has no effect on BP. There was a gender-related effect of alcohol intake in excess of two drinks per day on BP, with increased BP observed only in men but not in women.

Sex-/ovarian steroid-dependent release of endomorphin 2 from spinal cord.

Mu-opioid receptor (MOR) agonists have been shown to be more potent analgesics in male than female rodents. Regulation of spinal MOR-coupled antinociception by 17beta-estradiol (estrogen, E2) and progesterone (P) is also sexually dimorphic; pregnancy levels of E2/P activate MOR-coupled analgesic pathways in male but not female rats. We hypothesized that the sexual dimorphic characteristics of MOR-coupled antinociception reflects sexual dimorphism in the regulation of the release from spinal cord of the endogenous MOR agonist, endomorphin 2 (EM2). Parameters of spinal EM2 release manifesting sexual dimorphism include its 1) magnitude: in vitro basal and K+-evoked release of EM2 from spinal tissue of male rats is approximately 50% greater than that observed from spinal cord of females; 2) modulation by ovarian sex steroids: E2/P treatment significantly enhanced K+-evoked EM2 release from spinal tissue of males, but not females; and 3) enhancement by opioid receptor blockade: naloxone enhanced stimulated EM2 release from spinal tissue of both males and females, but it augmented basal release from spinal tissue of only males. Enhancement of EM2 release by naloxone reflects negative coupling of MOR to EM2 release and hence its modulation by negative feedback since only activation of MOR, not kappa-or delta-opioid receptors, was able to inhibit evoked EM2 release. These data reveal that the EM2-MOR spinal analgesic system is more robust and "higher gain" in male versus female rodents. These findings could provide a mechanistic rubric for understanding the male female dichotomy in prevalence and intensity of chronic pain syndromes.

Epidural pentobarbital delivery can prevent locally induced neocortical seizures in rats: the prospect of transmeningeal pharmacotherapy for intractable focal epilepsy.

PURPOSE: To determine whether epidural pentobarbital (PB) delivery can prevent and/or terminate neocortical seizures induced by locally administered acetylcholine (Ach) in freely moving rats. METHODS: Rats were implanted permanently with an epidural cup placed over the right parietal cortex with intact dura mater. Epidural screw-electrodes, secured to the cup, recorded local neocortical EEG activity. In the seizure-termination study, Ach was delivered into the epidural cup, and after the development of electrographic and behavioral seizures, the Ach solution was replaced with either PB or artificial cerebrospinal fluid (aCSF; control solution). In the seizure-prevention study, the epidural Ach delivery was preceded by a 10-min exposure of the delivery site to PB or aCSF. Raw EEG recordings, EEG power spectra, and behavioral events were analyzed. RESULTS: Ach-induced EEG seizures associated with convulsions, which were unaffected by epidural aCSF applications, were terminated by epidurally delivered PB within 2-2.5 min. Epidural deliveries of PB before Ach applications completely prevented the development of electrographic and behavioral seizures, whereas similar deliveries of aCSF exerted no influence on the seizure-generating potential of Ach. CONCLUSIONS: This study showed for the first time that epidural AED delivery can prevent, as well as terminate, locally induced neocortical seizures. The findings support the viability of transmeningeal pharmacotherapy for the treatment of intractable neocortical epilepsy.

PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo.

PNC-28 is a p53 peptide from its mdm-2-binding domain (residues 17-26), which contains the penetratin sequence enabling cell penetration on its carboxyl terminal end. We have found that this peptide induces necrosis, but not apoptosis, of a variety of human tumor cell lines, including several with homozygous deletion of p53, and a ras-transformed rat acinar pancreatic carcinoma cell line, BMRPA1. Tuc3. On the other hand, PNC-28 has no effect on untransformed cells, such as rat pancreatic acinar cells, BMRPA1, and human breast epithelial cells and no effect on the differentiation of human stem cells. In this study, we now test PNC-28 in vivo for its ability to block the growth of BMRPA1. Tuc3 cells. When administered over a 2-week period in the peritoneal cavities of nude mice containing simultaneously transplanted tumors, PNC-28 causes complete destruction of these tumors. When delivered concurrently with tumor explantation at a remote site, PNC-28 causes a complete blockade of any tumor growth during its 2-week period of administration and 2 weeks posttreatment, followed by weak tumor growth that plateaus at low tumor sizes compared with tumor growth in the presence of a control peptide. When administered after tumor growth has occurred at a site remote from the tumor, PNC-28 causes a decrease in tumor size followed by a slow increase in tumor growth that is significantly slower than growth in the presence of control peptide. These results suggest that PNC-28 may be effective in treating cancers especially if delivered directly to the tumor.

Conjugate eye movements and gamma power modulation of the EEG in persistent vegetative state.

BACKGROUND: Power in the gamma band EEG increases during saccades in normal subjects. OBJECTIVE: To develop a potential method to quantify signs of cortical responsiveness in persistent vegetative state (PVS) we quantified gamma range EEG in association with conjugate slow ballistic eye movements (SBEM). METHODS: The EEG and the simultaneous electro-oculogram were recorded in 14 (8F/6M) PVS patients. Clinical scoring was based on the Glasgow Coma Scale (GCS) and Coma Rating Scale (CRS). The Wavelet Transform, followed by Hilbert transform was applied to the EEG and gamma power distribution was quantified relative to the timing of an eye movement. We correlated the clinical and the neurophysiological measures. RESULTS: Gamma activity was present in all PVS patients. Its power was modulated in association with eye movements only in less severely affected patients, with minimum power prior to, and maximum power during the eye movement. In severely affected patients there was no evidence of a temporal relationship between gamma power and the phase of the eye movement. CONCLUSIONS: Detecting changes in the time course of gamma power in relation to conjugate ballistic eye movements provides a quantitative neurophysiological method for prospective longitudinal studies to explore if the preservation of this CNS function relates to the potential for recovery in PVS patients.

Further evaluation of plasma sphingomyelin levels as a risk factor for coronary artery disease.

BACKGROUND: Sphingomyelin (SM) is the major phospholipid in cell membranes and in lipoproteins. In human plasma, SM is mainly found in atherogenic lipoproteins; thus, high levels of SM may promote atherogenesis. METHODS: We investigated in a median follow up of 6.0 years the association of SM with the incidence of a combined endpoint (myocardial infarction and cardiovascular death) in stable and unstable patients, and its relation to other marker of atherosclerosis in 1,102 patients with angiographically documented CAD and 444 healthy controls. RESULTS AND DISCUSSION: Logistic regression analysis showed that SM categorized by median was associated with an elevated risk for CAD (HR 3.2, 95%CI 2.5-4.0, p < 0.05). SM levels were correlated with apoB (r = 0.34) and triglyceride levels (r = 0.31). In patients with stable angina (n = 614), SM categorized by median was not related to incidence of a combined endpoint (cardiovascular death and myocardial infarction) (p = 0.844 by Log-rank test). However, in patients with acute coronary syndrome (n = 488), elevated SM was related to the combined endpoint (p < 0.05 by Log-rank test), also in a multivariate Cox regression analysis including potential confounders (HR 1.8, 95%CI 1.0-3.3, p < 0.05). CONCLUSION: The results of our study reveal that 1) human plasma SM levels are a risk factor for CAD; 2) the pro-atherogenic property of plasma SM might be related to metabolism of apoB-containing or triglyceride-rich lipoproteins; and 3) plasma SM levels are a predictor for outcome of patients with acute coronary syndrome.

Serum sphingomyelin levels are related to the clearance of postprandial remnant-like particles.

It is known that sphingomyelin (SM) content is higher in apolipoprotein B-containing particles (BLps) than in high density lipoproteins and that BLp levels, including chylomicrons and their remnant particles, are positively related to atherosclerosis. To evaluate the relationship between serum SM and postprandial remnant particle levels, we determined SM, triglyceride (TG), and cholesterol levels in serum and in remnant-like particles (RLPs) before and 3, 5, 7, and 10 h after a high-fat meal in 31 healthy subjects. We found that serum SM, like serum TG, was increased to its maximum 3 h after fat loading and then gradually decreased to basal levels after 10 h. More important, we determined that SM and TG levels in RLPs were parallel. Serum SM was positively correlated with serum TG (P <0.001), RLP SM (P <0.001), RLP TG (P <0.001), and RLP cholesterol (P <0.001) levels. It is our conclusion that serum SM is a marker for the clearance of RLPs.

Control of cardiovascular risk factors in patients with diabetes and hypertension at urban academic medical centers.

OBJECTIVE: There are national mandates to reduce blood pressure (BP) to <130/85 mmHg, LDL cholesterol to <100 mg/dl, and HbA(1c) to <7% and to institute aspirin therapy in patients with diabetes. The objective of this study was to determine the proportion of patients in urban institutions with diabetes and hypertension who meet these treatment goals. RESEARCH DESIGN AND METHODS: Using American Diabetes Association (ADA) guidelines, we evaluated the control of cardiovascular disease (CVD) risk factors in 1,372 patients receiving medical care at two major urban medical centers in Brooklyn and Detroit. Information was extracted from charts of outpatient clinics. RESULTS: Of 1,372 active clinic patients with diabetes and hypertension, 1,247 (90.9%) had type 2 diabetes, and 26.7% met the target blood pressure of 130/85 mmHg. A total of 35.5% met the goal LDL cholesterol level of <100 mg/dl, 26.7% had an HbA(1c) <7%, and 45.6% were on antiplatelet therapy. Only 3.2% of patients met the combined ADA goal for BP, LDL cholesterol, and HbA(1c). CONCLUSIONS: Optimal control of CVD risk factors in adults with diabetes was achieved only in a minority of patients. Results reflect the inherent difficulties in achieving these complex guidelines in our present health care systems.