bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistant or Difficult‐to‐Treat Hypertension
Authors: Moser Marvin , Cushman William , Handler Joel
Published: February 2007

Following a hypertension symposium in Los Angeles, CA, in October 2005, an expert panel discussion was held to discuss resistant hypertension. Are there patients whose blood pressures cannot be controlled? Do inappropriate uses of medications or drug combinations or, on the other hand, poor adherence on the part of patients, play a major role in resistance? Dr. Marvin Moser, Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT, moderated the discussion. Participants on this panel included Dr. William Cushman of the University of Tennessee College of Medicine, Memphis, TN, and Dr. Joel Handler of the Kaiser Permanente Group in Anaheim, CA.
Physician Familiarity With Diagnosis and Management of Hypertension According to JNC 7 Guidelines
Authors: Sisson Stephen D. , Rastegar Darius , Rice Tasha N. , Prokopowicz Gregory , Hughes Mark T.
Published: February 2007

Physician knowledge of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines is unknown and may contribute to the prevalence of uncontrolled hypertension. Our objective was to determine physician knowledge of JNC 7 guidelines and whether online instruction could improve knowledge. A pretest served as baseline knowledge, and comparison with a post‐test after completing an online didactic demonstrated improvement in knowledge. Participants included 1280 physicians at 45 internal medicine residency training programs. Average baseline knowledge of six concepts of hypertension was 51.2%. Attending physicians performed better than trainees on some but not all concepts (p<0.05). Third‐year post‐graduate trainees performed better than first‐year trainees on some but not all concepts (p<0.05). Knowledge increased significantly on all concepts after completing the curriculum (p<0.05). The authors demonstrated that physician knowledge of JNC 7 guidelines is poor but can be improved by an online curriculum. Further study is needed to determine the impact of physician education on clinical outcomes in individuals with hypertension.
Atherosclerotic Renal Artery Stenosis and Renovascular Hypertension: Clinical Diagnosis and Indications for Revascularization
Authors: Kerut Edmund Kenneth , Geraci Stephen A. , Falterman Chester , Hunter David , Hanawalt Curtis , Giles Thomas D.
Published: February 2007

Atherosclerotic renal artery stenosis (RAS) is relatively common and often associated with reversible hypertension, progressive renal insufficiency, and/or coronary‐independent pulmonary edema. Not all RAS is associated with renovascular hypertension. Historical and physical findings may suggest renovascular hypertension and warrant investigation for RAS. Noninvasive diagnostic imaging options include renal artery duplex ultrasonography, magnetic resonance angiography, computed tomographic angiography, and CO2 angiography, with each method having its own advantages and limitations. Functional tests of renal flow, which characterize RAS significance, include captopril‐stimulated plasma renin activity and captopril renography. To date, no single approach has shown clear superiority either in diagnosis or identification of patients most likely to benefit from revascularization. Revascularization of RAS is recommended for severe/drug‐refractory hypertension, preservation of renal function, recurrent flash pulmonary edema, or recurrent severe heart failure. Intervention response is variable, but the ongoing Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, comparing medical therapy with and without stenting, should provide management guidance.
Arterial Elasticity and Erectile Dysfunction in Hypertensive Men
Authors: Prisant L. Michael , Loebl Don H. , Waller Jennifer L.
Published: February 2007

Erectile dysfunction is a common symptom among hypertensive patients that impairs quality of life and adherence to antihypertensive pharmacologic therapy. It is also associated with cardiovascular risk factors and disease. The Sexual Health Inventory in Men (SHIM) was administered to 105 ambulatory hypertensive patients, and large and small artery elasticity indices were measured. Each variable was examined in a simple linear regression model or 1‐way analysis of variance model to determine each variable's relationship with the SHIM score. Variables that were significantly associated with the SHIM score in the univariate models included age, duration of hypertension, peripheral vascular disease, and small artery elasticity. Large artery elasticity was not significantly associated with the SHIM score. In the multivariate model, age, hypertension duration, and peripheral vascular disease were associated with a lower SHIM score. This study demonstrates a relationship between erectile dysfunction and reduced artery elasticity.
Relation of Left Ventricular Hypertrophy to Regional Cerebral Blood Flow: Single Photon Emission Computed Tomography Abnormalities in Essential Hypertension
Authors: Sierra Cristina , Sierra Alejandro de la , Lomeña Francisco , Paré Juan Carlos , Larrousse María , Coca Antonio
Published: February 2007

Several reports have shown that left ventricular hypertrophy (LVH) is an independent predictor of acute cerebrovascular events. The aim of the present study was to investigate the relationship between LVH and cerebral blood flow in middle‐aged patients with essential hypertension. Forty never‐treated hypertensive patients (24 men, 16 women, aged 50–60 years) without clinical evidence of target organ damage were studied. Regional cerebral blood flow was measured by means of single photon emission computed tomography of the brain. Twenty‐nine patients showed echocardiographic criteria of LVH; 11 patients did not show this feature. No differences were found in regional cerebral blood flow ratio of all brain areas studied between hypertensives with or without LVH except for the striatum area. The regional cerebral blood flow ratio was significantly reduced in the striatum region of hypertensive patients with LVH, compared with patients without LVH (91.5±7.4 vs 98.1±8.3; P=.023). This relationship remained significant after adjusting for blood pressure. The authors conclude that the presence of LVH in middle‐aged patients with essential hypertension is associated with a reduction of regional cerebral blood flow in the striatum area.
Coronary Artery Bypass Surgery Versus Percutaneous Coronary Intervention with Drug‐Eluting Stent Implantation in Patients with Multivessel Coronary Disease
Authors: YANG ZHEN KUN , SHEN WEI FENG , ZHANG RUI YAN , KONG YE , ZHANG JIAN SHENG , HU JIAN , ZHANG QI , DING FENG HUA
Published: February 2007

Background: Drug‐eluting stents (DES) constitute a major breakthrough in restenosis prevention after percutaneous coronary intervention (PCI). This study compared the clinical outcomes of PCI using DES versus coronary artery bypass graft (CABG) in patients with multivessel coronary artery disease (MVD) in real‐world.

Methods: From January 2003 to December 2004, 466 consecutive patients with MVD underwent revascularization, 235 by PCI with DES and 231 by CABG. The study end‐point was the incidence of major adverse cardiovascular events (MACEs) at the first 30 days after procedure and during follow‐up.

Results: Most preoperative characteristics were similar in the two groups, but left main disease (24.7% vs 2.6%, P<0.001) and three‐vessel disease (65% vs 54%, P = 0.02) were more prevalent in CABG group. The number of coronary lesions was also greater in CABG group (3.7 ± 1.1 vs 3.3 ± 1.1, P<0.001). Despite higher early morbidity (3.9% vs 0.8%, P = 0.03) associated with CABG, there were no significant differences in composite MACEs at the first 30 days between the two groups. During follow‐up (mean 25±8 months), the incidence of death, myocardial infarction, or cerebrovascular event was similar in both groups (PCI 6.3% vs CABG 5.6%, P = 0.84). However, bypass surgery still afforded a lower need for repeat revascularization (2.8% vs 10.4%, p = 0.001). Consequently, overall MACE rate (14.5% vs 7.9%, P = 0.03) remained higher after PCI.

Conclusion: PCI with DES is a safe and feasible alternative to CABG for selected patients with MVD. The reintervention gap was further narrowed in the era of DES. Aside from restenosis, progression of disease needs to receive substantial emphasis.
Famprofazone as the Source of Methamphetamine and Amphetamine in Urine Specimen Collected During Sport Competition
Authors: Tseng Ying Lung , Lin Chien‐Tzong , Wang Sheng‐Meng , Liu Ray H.
Published: February 2007

ABSTRACT: During a sport competition event in Taiwan, one urine specimen was found positive for both methamphetamine (2688 ng/mL) and amphetamine (462 ng/mL). The specimen donor claimed that she had taken Gewolen® (a nonprescription drug manufactured in Taiwan) for treating abdominal pain and the medication was presented. Laboratory investigation confirmed that Gewolen® contains famprofazone, which is known to metabolize to methamphetamine and amphetamine and is included in the prohibited list of the World Anti‐Doping Agency. Study on the excretion profiles of three volunteers ingesting 50 mg famprofazone produced the following patterns similar to that observed in the case specimen: (a) the ratio of methamphetamine to amphetamine was approximately 6 to 1; (b) d‐ and l‐enantiomers of both methamphetamine and amphetamine were present, while the amount of l‐methamphetamine was 3–4‐fold greater than its counterpart. The data suggested that famprofazone (as the ingredient of Gewolen®) was likely the source of the prohibited drugs found in the case specimen.
Finding optimal price risk management instruments: the case of the Spanish potato sector
Authors: Bielza María , Garrido Alberto , Sumpsi José M.
Published: February 2007

This article offers a comprehensive analysis of the problem of choosing between alternative market risk management instruments. We model farmers' behavior to optimize the certainty equivalent, formulated by a mean–variance model, by combining instruments with and without basis risk. Results are expressed as the demands for hedging with futures, forward contracts and insurance. Theoretical results are applied to a selection of Spanish producers of fresh potatoes, a sector that is exposed to significant market risks. Amsterdam's Euronext provides potato futures prices, and the recently launched revenue insurance in Spain provides the example for price insurance. Three conclusions summarize the article's main findings. First, we show that Spanish potato revenue insurance subsidies are a factor that determines the instrument rankings and choice. Second, the efficiency of insurance subsidies is generally low. Finally, the Amsterdam potato futures market does not provide a cost‐effective means to manage price risks for Spanish fresh potato growers.
Social inequality in tooth extraction in a Brazilian insured working population
Authors: Neto Joaquim Murilo Silveira , Nadanovsky Paulo
Published: February 2007

Abstract –  Objectives:  Given the scant evidence of the socioeconomic gradient in tooth loss incidence, the purpose of this study was to compare the odds of individuals of distinct social strata being subjected to tooth extraction.

Methods:  We undertook a case–control study at the head office of a large Brazilian company whose employees had access to dental care through the company's dental insurance.

Results:  During 2 years of observation, 264 teeth were extracted and the distribution of such extractions was rather unequal. A strong suggestion of a social gradient was noted and the odds of tooth extraction occurring per social strata, adjusted by age and gender, were five times higher in employees pertaining to the lowest social stratum, when compared with those at the highest.

Conclusions:  We concluded that lower social strata were strongly associated with increased risk of having teeth extracted. Dental insurance was not able to equalize the chances of tooth extraction among different social strata, in a population of employed adults.
Quantitative Cytological Analysis of Functional Changes in Adrenomedullary Chromaffin Cells in Normal, Sham‐Operated, and Pinealectomized Rats in Relation to Time of Day: I. Nucleolar Size
Authors: Kachi T. , Banerji T.K. , Quay W.B.
Published: February 2007

Adrenaline (A)‐ and noradrenaline (N)‐cells in juxtacortical and central areas of adrenal medullas of nonoperated, sham‐operated, and pinealectomized male rats (n = 125) were investigated by quantitative electron and light microscopy. Animals were killed at eight time points during a standardized 24‐h, light‐dark (12:12) cycle 14 d after surgery. Diameters of nucleoli (n = 9,600) and the nucleolar margination rate were studied chiefly by light microscopy.

Major findings include the following: (1) Twenty‐four‐hour changes occurred in nucleolar diameters in adrenomedullary chromaffin cells in nonoperated animals, with the peak in the late dark phase (X ± SD, A‐cells: 1.29 $ 0.06 μm; N‐cells: 1.23 ± 0.05 μm) and the minimum in the mid‐light (A‐cells: 1.16 μ 0.04 μm) or early dark (N‐cells: 1.14 μ 0.03 μm) phase. (2) These changes were markedly dampened (diminished) in sham‐operated animals. (3) Since this dampening of time‐of‐day changes after sham‐operations was not seen in A‐cells after pinealectomy, mediation by the pineal gland of this dampening is suggested. (4) Pinealectomized animals showed 24‐h changes in nucleolar diameters, but these changes differed from those of nonoperated controls in their temporal and phase relations. For example, there was phase advance in A‐cells in the juxtacortical area and desynchronization in N‐cells. (5) Furthermore, rhythm amplitude was slightly increased in A‐cells and slightly decreased in N‐cells after pinealectomy. (6) A‐ and N‐cells differed from each other consistently and significantly in the quantitative morphology of their nuleoli and nuclei, and slightly in the patterns of their time‐of‐day changes in nucleolar size. (7) Nucleolar size usually showed a tendency for a regional gradient, decreasing slightly from periphery toward the center. These observations contribute to our understanding of the chronobiology and functional relations of adrenomedullary chromaffin cells, and of the effects of pinealectomy and sham operations upon this system.
Seasonal Changes in Glycogen Level and Size of Pinealocytes of the White‐Footed Mouse, Peromyscus leucopus: A Semiquantitative Histochemical Study
Authors: Kachi T. , Quay W.B.
Published: February 2007

Glycogen level in and size of pinealocytes of the feral, white‐footed mouse Peromyscus leucopus, were studied by a semiquantitative histochemical method to determine whether seasonal changes exist in them under natural conditions, what temporal pattern they exhibit, and whether 24‐hour changes in these parameters exist in different seasons, as shown in the laboratory dd‐mice. Marked seasonal changes were seen in both glycogen levels and nuclear densities (ANOVA P < 0.005). The size of pinealocytes at 09:00 to 10:00 showed one peak (and nadir) seasonal change, with the smallest size in winter (December and February) and a larger size in warmer seasons, with the maximum value in July. Glycogen level in pinealocytes at 09:00 to 10:00 showed bimodal seasonal changes, with lower levels in fall and spring and higher levels in winter and summer. In fall, a circadian trend in glycogen level in pinealocytes was seen, with a higher level at the end of the light period. In winter, the glycogen levels were very high at 09:00, 13:00, 17:00, and 21:00 examined and showed dampening of time‐of‐day differences. On the other hand, the size of pinealocytes followed a time‐of‐day change (P < 0.005), being largest at 13:00 and smallest at 21:00. Thus, marked changes in quantitative structure and chemical activities, suggesting changes in functional activity, in pinealocytes were noted especially in severe, cold winter.
Effects of Experimentally Induced Chronic Hyperprolactinemia on the Ultrastructure of Pinealocytes in Male Rats
Authors: Karasek Michal , Bartke Andrzej , Doherty Paul C.
Published: February 2007

The influence on the ultrastructure of pinealocytes of long‐term hyperprolactinemia caused by ectopic pituitary transplants and of suppression of prolactin release by bromocriptine was examined morphometrically in male rats. Hyperprolactinemia resulted in an increase in the relative volumes of granular endoplasmic reticulum, vacuoles containing a flocculent material, mitochondria, and lipid droplets. Treatment of grafted rats with bromocriptine reversed the effects of hyperprolactinemia. However, bromocriptine had no apparent influence on the pinealocytes of intact rats. The effects of hyperprolactinemia on the ependymallike secretory process in the pinealocyte were especially pronounced.
Characterization of a Pineal‐Mediated Inhibition of Pubertal Prolactin Cell Development in Blind‐Anosmic Female Rats
Authors: Leadem Christopher A. , Blask David E.
Published: February 2007

The purpose of this study was to define the peripubertal changes in prolactin (PRL) synthesis in blind‐anosmic female rats. To do this prepubertal female rats were either rendered blind‐anosmic (BA) or blind‐anosmic‐pinealectomized (BAP) or left intact (INT). Half the animals were killed after 1 wk (before puberty) while the remaining animals were terminated after 4 wk (after puberty). Pituitary PRL synthesis was measured by the in vitro incorporation of 3H‐leucine into PRL. Anterior pituitary weight and DNA content did not differ between BA, BAP, and INT animals 1 wk after treatment. There was a 65% increase in weight and a 55% increase in DNA content in INT pituitaries between I and 4 wk. White these increases were also present in BAP rats, they were almost entirely prevented in BA animals. PRL synthesis followed a similar pattern with a 78% increase in synthesis in INT groups between 1 and 4 wk which was, once again, almost entirely absent in BA rats. Pinealectomy prevented this effect. Blinding and anosmia in postpubertal animals produced only a minor decrease in PRL synthesis and pituitary weight and no decrease in pituitary cell number. From these data we conclude that the pineal can inhibit the normal proliferation of PRL cells that occurs during puberty in blind‐anosmic female rats.
An Immunocytochemical Study of the Luteinizing Hormone‐Releasing Hormone (LHRH) System in the White‐Footed Mouse: Effect of Blinding and Melatonin
Authors: Petterborg Larry J. , Paull Willis K.
Published: February 2007

Previous studies have provided evidence that pineal‐mediated gonadal atrophy involves the luteinizing hormone‐releasing hormone (LHRH) system in some rodents. The purpose of the present study was to visualize the LHRH system in the brain of the white‐footed mouse by immunocytochemical methods and to assess the influence of blinding or melatonin on the LHRH immunostaining characteristics of the median eminence. Six intact adult female mice and six adult males (two intact, two blinded, and two with subcutaneous melatonin‐beeswax implants) treated for 6 wk were sacrificed by perfusion of fixative, and their brains were removed, cut into 60‐μm sections and stained for LHRH by the peroxidase‐antiperoxidase (PAP) method. Since the tissues were batch‐processed in separate wells in a common chamber, semiquantitive comparisons may be made between similar sections from animals subjected to different treatments. The testes were also collected and prepared for microscopic examination. The distribution of LHRH‐stained cell bodies and fibers was found to be essentially the same as has been described in other rodents, i.e., predominantly confined to the preoptic area and hypothalamus. The perikarya appear as unipolar and bipolar fusiform cells with “beaded fiber” type processes. In sections that included the median eminence of the blinded and melatonin‐treated males, the degree of immunopositive staining appears to be greater than in the median eminence of untreated mice. The histological appearance of the testes from the treated animals revealed a profound inhibition of gametogenesis. These observations support the suggestion that pineal‐mediated gonadal atrophy is the result of an inhibition of LHRH release from the median eminence.
Melatonin and N‐Acetylserotonin Stress Responses: Effects of Type of Stimulation and Housing Conditions
Authors: Seggie Jo , Campbell Lynda , Brown Gregory M. , Grota Lee J.
Published: February 2007

The effects of housing condition and type of stimulation on serum melatonin and N‐acetylserotonin (NAS) were investigated. Male rats were housed under a 12/12‐ hour light‐dark cycle, with ad libitum food and water, either individually or in groups of four. At the start of the light phase, separate groups were sacrificed at rest or subjected for 3 minutes to the stimulation of cold water, noise, novel environment, or ether vapour and then decapitated at 0, 5, 15, 30 or 60 minutes after the end of stimulation. Melatonin was measured by a modified radioimmunoassay and NAS by a specific radioimmunoassay. Melatonin levels responded to stimulation with an increase, while NAS levels responded with a decrease. Housing condition had no effect on hormone response. However, the pattern of response for each of the two hornomes differed greatly among the stimuli. For melatonin, cold water was the most potent stimulus, followed by noise, novel environment, and ether. NAS responded most to ether, fleetingly to cold, and in a bimodal manner to noise. The data are interpreted as suggesting that separate mechanisms regulate serum melatonin and serum NAS is response to environmental stimulation and that under appropriate control conditions melatonin from the pineal is very responsive to environmental stimuli, in a manner similar to that of pituitary hormones.
Impact of Psychosocial Stress on Pineal Structure of Male Gerbils (Meriones unguiculatus, Cricetidae)
Authors: Heinzeller Thomas
Published: February 2007

Stress responses were investigated in 5‐month‐old male gerbils. Breeders having no pubescent litters served as controls. The first experimental group never left their parents’cage and were thereby fought by higher‐ranking males; the second and third groups were stressed for a week by four daily 1‐minute encounters with trained fighters, the second group during daytime, the third during the dark period. The first and second groups developed signs of gonadal regression, the third did not. The adrenals of the first group weighed the same as those of controls; the adrenals of both other groups were increased in weight. In the adrenal medulla of all experimental groups, a large number of cells were densely packed with noradrenaline‐containing vesicles. In each experimental group the pineal changes included a remarkable decrease in nuclear size of pinealocytes, an increased number of colloidal cysts, and a reduction of that portion of the plasmalemma that is lined by subsurface cisterns. All these changes are interpreted in terms of pineal activation, as are the increased number of membrane whirls found in the first group. The third group exhibited an additional decrease in the size of mitochondria and in the number of “synaptic” structures. This finding and the day‐night differences in the gonadal response indicate that stress interferes with the metabolic cyclicity of the pineal gland. However, it remains indiscernible whether the pineal stress reaction signals a general activation of the gland or a change in it's temporal activity patterns.
Inhibition of Serum Melatonin Concentration and Synthesis of Brain Indolealkylamines by Monofluoromethyldopa in the Rat
Authors: Bradbury Amanda J. , Giddins R. E. , Smith J. A.
Published: February 2007

The simultaneous effect of α‐monofluoromethyldopa (MFMD) on the synthesis of rat brain indolealkylamines has been investigated both in the daytime and in the dark phase. The effect on serum melatonin concentration has also been determined in the dark period. MFMD inhibits 5‐hydroxytryptophan decarboxylase in the pineal gland, hypothalamus, and the cerebral cortex. Simultaneous measurement of 5‐hydroxytryptophan (5‐HTP), 5‐hydroxytryptamine (5‐HT), and 5‐hydroxyindoleacetic acid (5‐HIAA) levels in the three brain areas revealed that MFMD caused (1) large increases in pineal 5‐HTP concentrations and substantial decreases in pineal 5‐HT and 5‐HIAA both in the light and dark phases; (2) a significant decrease in daytime hypothalamic 5‐HT content after 7‐h pretreatment; and (3) a large increase in dark‐phase cortical 5‐HT concentration after 4‐h pretreatment. Serum melatonin levels were also reduced by the action of MFMD in the dark period. The evidence suggests that differences occur in the rate‐limiting steps in the indolealkylamine biosynthesis in the three brain areas.
Phase Shift of Daily Profiles of N‐Acetyltransferase in the Rat Pineal Gland
Authors: White Beatrix H. , Mosher Karen , Binkley Sue
Published: February 2007

Pineal N‐acetyltransferase activity (NAT) has a circadian rhythm with peak values in the dark time and low values in the light time. NAT time profiles were measured in rats exposed to LD 14:10, to constant dark, and to acute (less than 48 hr) lightdark treatments.

In all experiments, imposition of light suppressed NAT. The phase of the dark time NAT cycle was altered 2 hr or less by the following treatments: 3 hr light in the early subjective night, 3 hr light in the late subjective night, 2 hr or 6 hr light in the early subjective day, 4 hr early lights‐on, 1 day of constant dark, or 1 day of constant light. When light was extended 4 hr into the dark time, NAT rose at lights out but fell again as the time of “expected” dawn approached.

In contrast, the phase of the NAT cycle was shifted 12 hr (180°) within 72 hr by reversing the phase of the light‐dark cycle. NAT did not rise in the first dark period (coincident with the time of the subjective light time). The amplitude of the first shifted cycle was less than four control NAT profiles measured in rats kept in the original (unshifted) light dark cycle.
Immunohistochemical Assessment of Melatonin Binding in the Pineal Gland
Authors: Holloway W. R. , Grota L. J. , Brown G. M.
Published: February 2007

Melatonin binding in the pineal gland of albino rats is estimated using an immunohistochemical procedure. Binding is saturable, has relatively high affinity (Apparent KD= 2.7 nM), and competition studies indicate binding of indoleamines possessing an N‐acetyl group on the terminus of the side chain (N‐acetylserotonin and melatonin). These data are consistent with the interpretation that immunohistochemically determined melatonin in unfixed pineal tissue is assessing binding of N‐acetylated indolealkylamines to pineal cell components.

In albino rats maintained on 12‐hour light: 12‐hour dark cycles, melatonin binding exhibits a diurnal rhythm with low levels of saturation (30%) early in the light and saturation by endogenous melatonin near the onset of darkness. An annual rhythm of melatonin binding was observed in albino rats with low levels during the summer and high levels during the winter. Other rats were maintained on 12‐hour light: dark cycles and fed for 2 hours either early in the light period or early in the dark period. For both morning‐ and evening‐fed animals, melatonin binding was high prior to feeding and dropped immediately after feeding. Changes in melatonin binding that occur in response to alterations of feeding and time of year suggest the possibility that this binding reflects a functional site for melatonin.
Evidence for Pineal Involvement in Timing Implantation in the Western Spotted Skunk
Authors: May Ron , Mead Rodney A.
Published: February 2007

Experiments were designed to test the hypothesis that the pineal gland mediates the effects of changing day length and thereby synchronizes implantation within the population of spotted skunks. Intact, sham‐superior cervical ganglionectomized (SCGx), SCGx, and SCGx/bilateral orbitally enucleated (BI) pregnant skunks were subjected to a natural photoperiod, and the duration of the preimplantation period was monitored. In a second set of experiments, melatonin was administered to pregnant skunks via two methods to determine whether or not this pineal hormone would mimic the effects of short day photoperiods or B 1 on duration of the preimplantation period. Bilateral SCGx, which presumably denervated the pineal, had no effect on the average duration of the preimplantation period (232 ± 57 vs. 199 ± 6 days). However, SCGx reversed the inhibitory effect of B1 on implantation as SCGx/B1 animals had an average duration of the preimplantation period that was not significantly different from intact controls (262 ± 46 vs. 214 ± 11 days) but was significantly shortened in comparison to enucleated animals (262 ± 46 vs. 316 ± 45 days). Melatonin significantly lengthened the duration of the preimplantation period in animals receiving either daily afternoon injections of melatonin or those receiving melatonin Silastic capsule implants. These results are consistent with the hypothesis that the pineal gland synchronizes photoperiod‐induced blastocyst implantation in the western spotted skunk.
A Fluctuation in Plasma Melatonin Level in the Weddell Seal During Constant Natural Light
Authors: Griffiths D. J. , Bryden M. M. , Kennaway D. J.
Published: February 2007

Blood was collected over a 24‐h period from free‐living adult Weddell seals that had been exposed to natural constant daylight for some 12 weeks. The plasma melatonin concentration was low throughout the trial (range of means: 30.8–70.4 pg/ml) with the exception of a 3‐h period centered on 1700 h local time, when the plasma level rose to a mean of 131.8 pg/ml. The pineal gland of the Weddell seal is thus capable of transient bouts of activity during constant and bright daylight, a situation usually inhibitory to the function of the gland. It is suggested that circadian fluctuations in the intensity of constant light entrain variation in the pineal gland functioning of this seal during summer.
Effects of Melatonin Implants on Structures and Behaviors of the House Finch (Carpodacus mexicanus) Eye
Authors: Quay W. B.
Published: February 2007

This study aimed to determine the extraretinal effects of melatonin upon the eyes of an avian species, the House Finch (Carpodacus mexicanus). Twelve birds (full‐grown, second‐year males) each received a Silastic tubing intraperitoneal implant, six containing melatonin (average release = 24μg/d/bird; = M birds) and six being empty (= C birds). Microscopic study of pupillary and palpebral behaviors during the final week demonstrated lesser pupillary diameters and interpalpebral distances in M birds under all test conditions. These effects could have diminished mean light levels reaching parts of the retina. Characteristics of the relative miosis and ptosis of M birds resemble signs in some CNS disorders, such as altered inhibition of the Edinger‐Westphal nucleus, and especially lesions in, or lowered activity of, higher sympathetic centers (a subtype of Horner's syndrome). Weights of eyes and their parts were the same in M and C birds, contrasting with previously reported results from male Golden Hamsters, possibly due to species differences and/or preexperimental attainment of full growth in the finches. Effects of melatonin on pupillary and palpebral behaviors, demonstrated here for the first time, foster caveats for simplistic experimental designs and interpretations with melatonin when sensory‐neural‐behavioral interactions are affected. Quantitative changes in pupillary and palpebral behaviors may, nevertheless, provide a window for monitoring central actions of melatonin in living test subjects in chronic studies.
Effect of Anticonvulsant Drugs In Vivo On Rat Pineal N‐Acetyltransferase (EC 2.3.1.5) and Hydroxyindole‐O‐Methyltransferase (EC 2.1.1.4)
Authors: Morton Dougal J.
Published: February 2007

The effect of anticonvulsant drugs on daytime and nighttime N‐acetyltransferase (NAT) and hydroxyindole‐O‐methyltransferase (HIOMT) levels was investigated. Some of the drugs caused a significant reduction in daytime NAT and HIOMT levels, possibly owing to beta‐receptor blockade although other mechanisms cannot be excluded. Sulthiame caused an increase in daytime NAT levels, and this may represent a compensatory mechanism by the pineal gland to allow normal melatonin production. None of the drugs affected nocturnal HIOMT levels, and only phenobarbitone affected NAT levels, apparently causing a shift in the nocturnal peak later in the dark phase.
Purification of Rat Pineal Hydroxyindole‐O‐Methyltransferase Using S‐Adenosyl‐L‐Homocysteine Agarose Chromatography
Authors: Sugden David , Voisin Pierre , Klein David C.
Published: February 2007

Rat pineal hydroxyindole‐O‐methyltransferase (HIOMT; EC 2.1.1.4) was purified by affinity Chromatography using an S‐adenosyl‐L‐homocysteine agarose column. This single‐step procedure, which is rapid, simple, and applicable to small quantities of tissue, gave a large enrichment of a protein (Mr∼ 38,000) identified by SDS‐PAGE and silver staining. The amino acid composition of rat HIOMT was generally similar to that of the bovine enzyme, although some differences were apparent. This method will be valuable in isolating sufficient rat HIOMT to enable its primary amino acid sequence to be determined.
Effects of Melatonin on Adrenomedullary Dopamine‐β‐Hydroxylase Activity in Golden Hamsters: Evidence for Pineal and Dose Dependencies
Authors: Banerji T. K. , Quay W. B.
Published: February 2007

Pineal influence in the control of adrenomedullary function in golden hamsters was investigated by examining changes in adrenal dopamine‐β‐hydroxylase (DBH) activity following pinealectomy, either alone or in combination with melatonin administration. Adult males acclimated to an LD 14:10 photoperiod were distributed in five experimental groups: intact controls (NO), sham‐pinealectomized (S), sham‐pinealectomized with black plastic shielding of the pineal region, pinealectomized (PX), and pinealectomized with the operated region shielded. Animals representing all of these groups were injected (between L11 and L11.75) with either vehicle, or a low dose (25 μg) or a high dose (2,500 μg) of melatonin daily for 28 days, after which they were killed, and the adrenals were collected for assay of DBH activity by means of a sensitive radioenzymatic method. We found that (1) PX + vehicle led to increased (P <.05) adrenal DBH activity in comparison with either NO or S groups; (2) daily 25 μg of melatonin resulted in lowered DBH activity in the NO group when compared with NO + vehicle (P <.001) or S + vehicle (P <.001) groups; (3) PX + 25 μ melatonin reversed the action of 25 μg melatonin in the NO + 25 μg group; (4) 2,500 μg melatonin was without effect on adrenal DBH in any of the injected surgical groups. These results show an inhibitory pineal influence on adrenal DBH activity, and that this was dose dependent. Furthermore, the inhibitory effect of exogenous melatonin on adrenomedullary DBH activity depended upon the presence of the pineal, suggesting a mediating role of the pineal in this particular action of melatonin. Since DBH catalyzes dopamine conversion to norepinephrine, a hormone and hormone precursor of the adrenal medulla, these results demonstrate, within at least one time frame, an inhibitory action of the pineal and melatonin on adrenomedullary catecholaminergic function.
Ultrastructural Demonstration of Exocytosis in the Pineal Gland
Authors: Masson‐Pévet Mireille , Pévet Paul , Noteborn Hub P.J.M.
Published: February 2007

Granular vesicles are present in pinealocytes and in rudimentary photoreceptor cells of many vertebrates, sometimes in large amounts. Their dense cores have been shown to store proteinaceous compounds, but the way they are released remains speculative. The aim of this study was to demonstrate whether or not exocytosis is the mechanism by which secretory products stored within granular vesicles are released. Therefore, a method has been used allowing a clear ultrastructural study of secretory products by exocytosis, even in tissues in which this process of secretion is quite rare and/or very slow. Exocytotic figures have been clearly demonstrated in the three species studied: golden hamster, snake, and parakeet. Nevertheless, they were never commonly observed as it was the case in neurohypophysis, even in such animals as the parakeet and snake, in which granular vesicles are very numerous. The possible reasons of this observation are discussed.
The Pattern of Motor Activity, Light, and Melatonin Production in Syrian Hamsters
Authors: Korenman E.M.D. , Watson B.W. , Silman R.E.
Published: February 2007

To investigate the motor rhythm of the Syrian hamster under natural photoperiod and to relate these findings to pineal rhythm, animals were left undisturbed in metabolic cages in which stabilimeter systems registered motor activity, photovoltaic cells registered light intensity, and in which urinary output was used for the assay of the major melatonin metabolite 6‐sulphatoxymelatonin. The motor activity of two animals was monitored during 1 month and showed a striking similarity. Melatonin secretion was measured during 3 consecutive days and showed a night/day ratio in both animals that was relatively constant and that was coupled to the diurnal rhythm of the animals' activity.
The Isolation, Purification, and Characterisation of the Principal Urinary Metabolites of Melatonin
Authors: Leone A.M. , Francis P.L. , Silman R.E.
Published: February 2007

Melatonin is metabolised by hydroxylation to form 6‐hydroxy‐melatonin by demethylation to form N‐acetyl‐serotonin, which are excreted as sulphate glucuronide conjugates. We required these metabolites as pure powders therefore undertook their isolation characterisation. Three volunteers ingested 1 g each of melatonin, their urine was collected pooled. For the sulphate conjugates, a Lichoprep column was used to concentrate the metabolites to remove most of the urea. The sulphate conjugates were separated from the glucuronides on a Florisil column further purified on a fractogel column. They were separated by high‐performance liquid chromatography (HPLC) resulting in white powders of 6‐hydroxy‐melatonin sulphate (SaMT) N‐acetyl‐serotonin sulphate (SNAS). For the glucuronide conjugates, an aliquot of the pooled urine was taken to dryness, the residue was dissolved in methanol, the solution was filtered. The methanol filtrate was taken to dryness, the residue was applied to a Florisil column. The isolated glucuronide conjugates were recrystallized prior to separation by HPLC, which gave pure white powders of N‐acetyl‐serotonin glucuronide (GNAS) 6‐hydroxy‐melatonin glucuronide (GaMT). Characterisation was achieved by using infrared ultraviolet spectroscopy, thin‐layer chromatography (TLC), gas chromatography‐mass spectrometry (GCMS). These techniques unambiguously confirmed the assigned structures for SaMT SNAS fully supported the assigned structures for GNAS GaMT. Three TLC solvent systems were used, in each case the individual conjugated metabolite appeared as a discreet spot. Purity, as assessed by GCMS, was shown to be greater than 95% for SNAS, SaMT, GaMT to be 88% for GNAS.
Lower Tryptophan:Phenylalanine Ratios in Culture Media Increase Medium: Pineal Melatonin Ratios in Early Dark but not Late Light Phase
Authors: Catalá M.D. , Quay W.B. , Timiras P.S.
Published: February 2007

Pineals from male Long‐Evans rats (60–65 days old; adapted to a 0700–1900 photoperiod) were cultured for 6 h either in light (1200–1800) or in dark (1800–2400). The objective was to ascertain the effects of tryptophan (trp) phenylalanine (phe) levels ratios in the culture medium on melatonin levels in the pineals their respective media. Total culture (pineal + medium) melatonin levels, determined by RIA, were similar under all conditions. However, in cultures during the early dark phase (1800–2400) lower trp:phe ratios in the medium led to lower pineal:medium ratios of melatonin content. In cultures during the late light phase (1200–1800) the trp:phe ratio had little impact on the pineal:medium distribution of melatonin. Trp:phe ratio rather than absolute level of either amino acid appeared responsible for this effect. Functionally this means that during early dark phase, but not late light phase, movement of melatonin from cultured pineal to medium is progressively facilitated by lower trp:phe ratios. It remains to be determined to what extent darkness per se and/or endogenous pineal rhythmic mechanisms have a permissive role in the action of trp:phe ratio on pineal melatonin release. A melatonin compartmentalization/release effect of these or other amino acids, or their ratios, has not been reported previously may possibly contribute to mechanisms for melatonin's transport or release at night.
Mechanism of Inhibition of Bovine Pineal Gland Hydroxyindole‐O‐Methyltransferase (EC 2.1.1.4) by Divalent Cations
Authors: Morton Dougal J.
Published: February 2007

The effect of inhibitory cations on hydroxyindole‐O‐methyltransferase (HIOMT) was investigated in order to elucidate the mechanisms involved. Copper inhibition of HIOMT can be classified as partial, classic noncompetitive inhibition with respect to S‐adenosyl methionine and as partial, mixed noncompetitive inhibition with respect to N‐acetylserotonin. Binding of copper to the enzyme impaired but did not prevent catalysis, and the difference in inhibitory pattern observed with both substrates may be due to the obligatory order of substrate binding to HIOMT. Calcium and magnesium were uncompetitive inhibitors of HIOMT with respect to both substrates and binding of these cations to the enzyme prevents catalysis. The cations presumably bind to HIOMT in the vicinity of the catalytic site and in some way prevent or impair the catalytic process, possibly by interfering with substrate binding to the enzyme, interfering with methyl transfer or product release after catalysis, or a combination of these effects. The different inhibitory patterns observed may result from differences in molecular size or outer electron shell valence of the cations.
Effects of Superior Cervical Preganglionectomy on Nerve Vesicles and Synaptic Ribbons in the Cat Pineal Gland
Authors: González Gabino , Alvarez‐Uría Manuel
Published: February 2007

Previous studies have shown that bilateral preganglionectomy of the superior cervical ganglia (SCGp) modifies the nerve vesicles and synaptic ribbons in the cat pineal gland. In the present study the nerve vesicles (NV) and synaptic ribbons (SR) were analyzed morphometrically after chronic preganglionectomy of the pineal sympathetic nerve fibers. It was shown that bilateral sympathectomy of the preganglionic fibers innervating the superior cervical ganglia (SCG) markedly reduces the number of dense cores of small dark vesicles (SDV) and, on the other hand, modifies the number and shape of the large dark vesicles (LDV). An increase in the number of the synaptic ribbons after chronic preganglionectomy of the SCG supports the hypothesis that the numerical reduction of dense cores of nerve vesicles in the cat pineal gland influences the level of synaptic ribbon formation.
Distribution in the Macaque Pineal of Nerve Fibers Containing Immunoreactive Substance P, Vasopressin, Oxytocin, and Neurophysins
Authors: Ronnekleiv Oline K.
Published: February 2007

The distribution of nerve fibers containing immunoreactive substance P (SP), estrogen‐stimulated neurophysin (ESN), nicotine‐stimulated neurophysin (NSN), oxytocin (OT), and vasopressin (VP) was examined in the epithalamic area of adult male and female macaques. Perfused or immersion‐fixed epithalamic tissues, sectioned, and mounted on glass slides were processed through the avidin–biotin immunofluorescence method.

Fibers containing immunoreactive SP were observed in the pineal organ along the periphery, in the perivascular space, and dispersed between the pinealocytes. Fibers were often observed in the pineal stalk region, and the habenular nuclei had high concentration of immunoreactive SP. Immunoreactive ESN fibers were observed in the stria medullaris, in the lateral habenula, in the pineal stalk, and in the pineal organ. Within the pineal, fibers containing ESN were present in the perivascular space, often concentrated in the walls of blood vessels, but also dispersed between pineal cells. Fibers containing OT, NSN, and VP were also present in the macaque pineal, but in lower quantities compared with fibers containing ESN.

These studies show that the pineal of subhuman primates contain nerve fibers (ESN, NSN, VP, OT) of possibly hypothalamic origin. It also has a rich supply of SP fibers, which might be of habenula origin, peripheral parasympathetic ganglia origin, or both. The functional significance of these peptidergic nerve fibers remains to be determined. However, there are indications that they might be involved in regulation of blood flow and release of secretory products from the pinealocytes.
Rhythms in Pineal Immunoreactive Somatostatin in the Syrian Hamster, Mouse, and Gerbil
Authors: Webb Susan M. , Peinado Miguel‐Angel , Puig‐Domingo Manuel , Viader Mercedes , Reiter Russel J.
Published: February 2007

Immunoreactive somatostatin (IRS) has been previously demonstrated in the pineal gland of different rodent species, and we observed a 24‐hr rhythm in rats. Recent data suggest that the peptide may represent a neurotransmitter in the so‐called peptidergic nerves of the central, pinealopetal innervation of the epiphysis, which may modulate the activity and secretion of the gland. We investigated whether 24‐hr changes of pineal IRS content occurred in Syrian hamsters, gerbils, and mice. Adult males, kept in a 14:10 LD photoperiod, were decapitated at 4‐hr intervals throughout a 24‐hr period. Pineals and median eminences were analyzed for IRS by radioimmunoassay. No significant changes in the median eminence content of IRS with time was observed. As previously described in rats, a statistically significant rhythm of IRS was observed in the pineal of hamsters and mice, with a peak at 2000 hr (mice 51.7 ± 5 pg/pineal; hamsters 26.3 ± 4.6) and a nadir at 2400 hr (mice 30.8 ± 1.4) or 0400 hr (hamsters 8.6 ± 1). However, in the gerbil pineal IRS content remained unchanged throughout the period of study. Since the three species examined have very different melatonin cycles, it is suggested that the melatonin and IRS rhythms are unrelated and independently regulated events within the pineal gland.
Secretory Patterns of Pineal Melatonin in the Rat
Authors: Pang S. F. , Yip P. C. Y.
Published: February 2007

The release patterns of pineal melatonin were studied by continuously monitoring melatonin levels in the confluens sinuum plasma in sighted and bilaterally enucleated rats in the light and dark periods. Plasma melatonin was determined by radioimmunoassay, and the data were analyzed by a computerized algorithm developed in our laboratory. Pulsations of melatonin levels were found in the confluens sinuum plasma in all the animals studied, suggesting episodic secretion of pineal melatonin in rats. Because the minimum melatonin levels in the confluens sinuum were over three times the melatonin levels in the general circulation, it is postulated that 1) there is an episodic release pattern of pineal melatonin superimposed on a basal release pattern and 2) there are two pools of melatonin in the pineal gland, a readily releasible pool responsible for the basal release and a bound pool responsible for the pulsatile release. In the sighted rats, there was no diurnal difference in mean melatonin concentration, mean pulse amplitude, mean pulse rate, mean minimum melatonin level, and mean maximum melatonin level in the confluens sinuum. In the bilaterally enucleated rats, with the exception of the mean pulse amplitude, diurnal rhythms were demonstrated in all the other parameters studied with, higher values in the dark period. This experimental model should be employed in future investigations on the regulation of secretory patterns of pineal melatonin. Results of these studies may provide important insight into the regulation of pulsatile release of neuroendocrine secretions in general.