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The feasibility of non-invasive analysis of brain activities was studied in the attempt to overcome the major limitation of actual in vivomethodologies, i.e. invasiveness. Optic fibre probes were used as the optical head of a novel, highly sensitive near-infrared continuous wave spectroscopy (CW-NIR) instrument. This prototype was designed for non-invasive analysis of the two main forms of haemoglobin: oxy-haemoglobin (HbO2) and deoxy-haemoglobin (Hb), chromophores present in biological tissues. It was tested in peripheral tissue (human gastrocnemius muscle) and then reset to perform the measurement on rat brain. In animal studies, the optical head was firmly placed using stereotaxic apparatus upon the sagittal line of the head of anaesthetized adult rats, without any surgery. Then pharmacological treatments with saline (300 µl s.c.) amphetamine (2 mg kg?1) or nicotine (0.4 mg kg?1) were performed. Within 10-20 min amphetamine substantially increased HbO2and reduced Hb control levels. Nicotine produced a rapid initial increase followed by a decrease in HbO2. In contrast to amphetamine, nicotine treatment also reduced Hb and blood volume. These results support the capacity of our CW-NIR prototype to measure non-invasively HbO2and Hb levels in the rat brain, that are markers of the degree of tissue oxygenation, thus providing an index of blood levels and therefore of brain metabolism.

The adrenal production of the Δ5-androgens, dehydroepiandrosterone (DHEA) and its sulfate ester dehydroepiandrosterone sulfate (DHEAS), declines linearly with aging. The evidence that DHEA or DHEAS administration may alleviate some of the problems related to aging has opened new perspectives for clinical research. The present study aims to investigate the effects of a 6-month DHEA supplementation in early and late postmenopausal women, with normal or overweight body mass index (BMI), on the level of circulating steroids, sex hormone binding globulin (SHBG), β-endorphin and gonadotropins, and on the adrenal gland response to dexamethasone suppression and adrenocorticotropic hormone (ACTH) stimulation.Early postmenopausal women (50-55 years) both normal weight (BMI 20-24, n = 9) and overweight (BMI 26-30, n = 9) and late postmenopausal women (60-65 years) both of normal weight and overweight, were treated with oral DHEA (50 mg/day). Circulating DHEA, DHEAS, 17-OH pregnenolone, progesterone, 17-OH progesterone, allopregnanolone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, SHBG, Cortisol, luteinizing hormone, follicle stimulating hormone and β-endorphin levels were evaluated monthly and a Kupperman score was performed. The product/precursor ratios of adrenal steroid levels were used to assess the relative activities of the adrenal cortex enzymes. Before and after 3 and 6 months of therapy, each women underwent an ACTH stimulating test (10 μgi.v.in bolus) after dexamethasone administration (0.5 mg p.o.) to evaluate the response of Cortisol, DHEA, DHEAS, androstenedione, 17-OH pregnenolone, allopregnanolone, progesterone and 17-OH progesterone.The between-group differences observed before treatment disappeared during DHEA administration. Levels of 17-OH pregnenolone remained constant during the 6 months. Levels of DHEA, DHEAS, androstenedione, testosterone and dihydrotestosterone increased progressively from the first month of treatment. Levels of estradiol and estrone significantly increased after the first/second month of treatment. Levels of SHBG significantly decreased from the second month of treatment only in overweight late postmenopausal women, while the other groups showed constant levels. Progesterone levels remained constant in all groups, while 17-OH progesterone levels showed a slight but significant increase in all groups. Allopregnanolone and plasma β-endorphin levels increased progressively and significantly in the four groups, reaching values three times higher than baseline. Levels of Cortisol and gonadotropins progressively decreased in all groups.The product/precursor ratios of adrenal steroid levels at the sixth month were used to assess the relative activities of the adrenal cortex enzymes and were compared to those found before therapy. The 17,20-desmolase, sulfatase and/or sulfotransferase, 11,20-lyase and 5α-reductase activities significantly increased, while the 3β-hydroxysteroid-oxidoreductase activity did not vary. On thecontrary, the 11-hydroxylase and/or 21-hydroxylase activities showed a significant decrease after 6 months of treatment.In basal conditions, dexamethasone significantly suppressed all the adrenal steroids and this suppression was greater after 3 and 6 months of treatment for DHEA, DHEAS and allopregnanolone, while it remained unchanged for other steroids. Before treatment, ACTH stimulus induced a significant response in all parameters; after the treatment, it prompted a greater response in Δ5-and Δ4-androgens, progesterone and 17-OH progesterone, while Cortisol responded less in both younger and older normal-weight women. The endometrial thickness did not show significant modifications in any of the groups of postmenopausal women during the 6 months of treatment. Treatment with DHEA was associated with a progressive improvement of the Kupperman score in all groups, with major effects on the vasomotor symptoms in the early postmenopausal women.In conclusion, the present findings confirm that DHEA supplementation produces physiological and supraphysiological modifications in steroid milieu and adrenal function. The beneficial effects of DHEA on the quality of life and in reverting the aging process may be related to changes in the release of adrenal products and/or peripheral steroids, with an increase in anxiolytic (allopregnanolone), anabolic (androstenedione, testosterone, dihydrotestosterone) and estrogenic (estrone, estradiol) molecules, a beneficial decrease in Cortisol and increase in pituitary β-endorphin production.

New estradiol (E2) transdermal matrix patches developed for once-a-week application, releasing 25 μg E2 (7D-25) or 50 μg E2 (7D-50) daily, were investigated in comparison with a placebo patch and the twice-weekly parent patch releasing 50 μg E2 (Derm-50) daily. Three hundred and eleven postmenopausal patients suffering at least seven hot flushes daily were randomly assigned to the four parallel groups and treated continuously for 12 weeks without progestin opposition.The daily number of hot flushes significantly decreased in all groups. At the 12th week the decrease from a baseline average of eight to nine episodes per day was 78% with 7D-25, 93% and 97% respectively with 7D-50 and Derm-50, and significantly (p < 0.001) lower with placebo (59%). Comparable efficacy was observed in terms of severity of hot flushes, Kupperman Index and patient self-rated overall efficacy.Minor systemic adverse events occurred in 10.0%, 8.8%, 16.9%) and 13.5% patients in the placebo, 7D-25, 7D-50 and Derm-50 groups respectively. Occasional mild and transient itching and/or erythema at the site of application was reported by a few patients, with no difference between groups or between once-weekly or twice-weekly application.In conclusion all E2 patches were significantly more effective than placebo in relieving climacteric symptoms in a dose-dependent fashion and all were well tolerated.

The aim of the study was to investigate the effects of estrogen replacement therapy (ERT) on nitric oxide (NO) activity in healthy postmenopausal women.The study group consisted of 22 postmenopausal women (last menses at least 12 months prior to study entry) who were randomized to receive treatment for 2 months with patches that delivered either 50 μg/day of 17β-estradiol or placebo in a cross-over design. Blood samples for measurements of serum citrulline and arginine were collected at the start of the study and at the end of each treatment course. Serum citrulline and arginine were measured using high-performance liquid chromatography with fluorometric detection.Arginine levels were significantly lower in the ERT group compared to the placebo group, while citrulline levels did not change. The percentage citrulline/arginine ratio was significantly higher in the ERT group (42.9 pm21.6) compared to the placebo group (33.9 pm18.5) (p < 0.01). The citrulline/arginine ratio, both at baseline and during either ERT or placebo administration demonstrated a positive linear correlation with body mass index (BMI). No correlations were found between follicle stimulating hormone, estradiol and insulin levels and BMI. No correlations were found between age, time since menopause and baseline arginine and citrulline levels or the citrulline/arginine ratio.These data indirectly demonstrate that transdermal estradiol replacement in postmenopausal women is able to stimulate NO production through the involvement of endogenous L-arginine. A positive linear correlation was found between BMI and the citrulline/arginine ratio, suggesting an additional protective cardiovascular effect in overweight women.

Multimodality evoked potentials (somatosensory and acoustic) have been recorded before surgery in children selected for surgical treatment for different kinds of craniostenosis and craniofacial stenosis. Evoked potentials were found to be deranged on at least one recording in 50 of cases, suggesting a significant incidence of neurophysiological alterations in these patients. No correlation was found between evoked potentials' derangements and clinical status, radiological findings, or different kinds of craniostenosis; moreover, a significant correlation was found between neurophysiological alterations and the age of the children. These preliminary data might define the possible role of neurophysiological tests-in the presurgical-evaluation of craniostenosis and craniofacial stenosis.

Cholecystokinin (CCK) is the major hormonal stimulus of gallbladder contraction. Both somatostatin and CCK-A receptor antagonists inhibit stimulation of the gallbladder by CCK. The aim of this study was to compare the effect of somatostatin and the CCK-A receptor antagonist loxiglumide (CR 1505) on gallbladder volume at baseline and after feeding.

The aim of the present study was to assess the effects of the new fluorine pro-drug monofluorophos-phate (MFP) in postmenopausal women with vertebral osteopenia and high bone turnover. We enrolled postmenopausal women (PMW, 43–59 years) who had had a natural menopause 2–5 years before the study, had vertebral bone mineral density (BMD) <13 SD from the premenopausal mean, and had at least one of the biochemical markers of bone remodeling >1 SD over the mean for premenopausal women. Patients were randomly divided into two treatment groups (group 1, 500 mg/day of oral calcium; group 2, MFP at the dose of 20 mg F-equivalents + 600 mg calcium/day) for 2 years (n=21 in each group). The lumbar vertebral (L2–4) BMD and total body bone mineral (TBBM) were measured by dual-energy X-ray absorptiometry (Lunar DPX, Lunar Corporation, USA). Urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla protein (BGP) and serum alkaline phosphatase (AP) were assayed. In group 1 the markers of bone turnover and vertebral BMD did not show any significant modification, while TBBM showed a significant (p<0.05) decrease after 24 months. In group 2 a significant (p<0.05) decrease in OH-P/Cr (-23.9±2.0%), and an increase in both BGP (+19.4±2.6%) and AP(+10.3±2.6%) levels were observed after 24 months of MFP administration. In this group, both vertebral BMD (+5.01±0.9%,p<0.01) and TBBM (+4.0±0.6%,p<0.05) showed a significant increase after 24 months. Present results suggest that, in osteopenic PMW, MFP administration induces a significant increase in vertebral BMD without impairment of cortical bone, with a reduction in bone resorption and an increase in bone formation rate.

The effects of i.a. injected cholecystokinin (CCK)-octapeptide on pyloric and antroduodenal motility, measured with strain gauges and combined side hole-sleeve manometry, were investigated in 16 dogs in vivo. CCK-octapeptide (OP) induced strong pyloric contractions when injected into the pylorus (threshold of 2 x 10(-13) mol; ED50, 8 x 10(-13) mol). Similar responses were obtained in the distal antrum (threshold, 6 x 10(-13) mol; ED50, 3 x 10(-12) mol) and the proximal duodenum (threshold, 5 x 10(-13) mol; ED50, 3 x 10(-12) mol). The nonsulfated form of CCK-OP was about 2 to 3 log units less potent in eliciting these excitatory responses in the pylorus (threshold, 9 x 10(-10) mol). Atropine shifted the dose-response curve of CCK-OP in pylorus, duodenum and antrum to the right suggesting a neural action of CCK-OP. However, an excitatory effect of CCK-OP was still present after neural blockade with tetrodotoxin i.a. Therefore, there was probably a muscular as well as a neural site of action of CCK-OP in these tissues. Systemic application of the novel CCK-antagonist CR-1392 in a dose of 1.2 mg/kg i.v. plus 100 micrograms i.a. shifted the dose-response curve of CCK-OP 1 log unit to the right without affecting the dose-response curve to acetylcholine. This dose of CR-1392 did not interfere with the pyloric motor responses to duodenal field stimulation or to intraduodenal acid infusion. These results demonstrate the dual peripheral action on nerve and muscle of CCK-OP in the pylorus in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystokinin (CCK) decreases lower esophageal sphincter pressure (LESP) in man. Cholestyramine, a nonabsorbable bile salt binding resin, stimulates endogenous CCK secretion. We have investigated the effect of oral ingestion of 16 g cholestyramine without and with infusion of the CCK receptor antagonist CR1505 (loxiglumide, 15 mg/kg/90 min) on LESP in seven healthy subjects. LESP was recorded for 90 min, in 10-min intervals, with the pull-through technique using a four-lumen water-perfused catheter. Oral ingestion of cholestyramine resulted in a significant (P<0.05) decrease in LESP, starting from 10 min and continuing during the entire experiment (basal LESP: 11.8±2 mm Hg, minimal value reached during cholestyramine: 7.3±1 mm Hg;P<0.05). Pretreatment with loxiglumide completely antagonized the effect of cholestyramine on LESP. Infusion of loxiglumide without cholestyramine did not affect basal LESP. It is concluded that: (1) cholestyramine significantly reduces LESP; (2) this reduction in LESP does not occur after pretreatment with loxiglumide, indicating that cholestyramine influences LESP through CCK release; and (3) basal LESP is not regulated by CCK.

A nonincremental interferometer for the absolute measurement of distances is presented. The measuring technique is based on both dispersive white-light (DWL) interferometry and frequency-modulated continuous-wave (FMCW) interferometry. The proposed configuration integrates both techniques in the same interferometer by use of a single laser diode. This solution enables the results from the coarse measurements from the FMCW interferometer to be combined with the fine readouts from the DWL interferometer. Preliminary experimental results confirm the capability of the system to combine the advantages of the two techniques.

Proglumide, a cholecystokinin antagonist, did not improve Parkinson's disease in a preliminary drug treatment trial.

A new single stage, low noise, shaper-preamplifier for optical gated signals is described. Careful layout and accurate component selection allow the use of CMOS analogue switches before signal amplification without deterioration of the noise performance of the preamplifier. With a silicon photodiode, the minimum detectable signal is less then 3000 photons for a pulse duration of 960 µs at λ = 810 nm.

On the basis of the theory of light scattering, photon correlation spectroscopy has been used for more than three decades to study ocular tissues. From first in-vitro experiments to study cataractogenesis, this approach has been extended to characterize semi-quantitatively in-vivo all the ocular tissues from cornea to retina and choroids. In order to acquire high quality measurement data from the experiments, serious attention has to be paid to the detector and processing system performance. Detector noise, sensitivity, dead time and afterpulsing lead to a direct or indirect corruption of the acquired correlation function whereas counting range and resolution should be optimized to take into account the wide variability of the ocular tissue optical characteristics.

Purpose:Our aim was to detect motion of scattering sites during transpupillary thermotherapy (TTT) using diffusing-wave-spectroscopy technique

Purpose:Neurovascular coupling at the optic nerve is the mechanism that adjusts blood flow in the microcirculation of the optic nerve to support the neural activity induced by vision.

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