bluuebunny/crossref_metadata_2025 huggingface dataset:
A highly sulfated chondroitin sulfate preparation, CS‐E, prevents excitatory amino acid‐induced neuronal cell death
Authors: Sato Yoshiaki , Nakanishi Keiko , Tokita Yoshihito , Kakizawa Hiroko , Ida Michiru , Maeda Hiroshi , Matsui Fumiko , Aono Sachiko , Saito Akiko , Kuroda Yoshiyuki , Hayakawa Masahiro , Kojima Seiji , Oohira Atsuhiko
Published: February 2008

J. Neurochem. (2008) 104, 1565–1576.

Chondroitin sulfate (CS) is a major microenvironmental molecule in the CNS, and there have been few reports about its neuroprotective activity. As neuronal cell death by excitotoxicity is a crucial phase in many neuronal diseases, we examined the effect of various CS preparations on neuronal cell death induced by the excitotoxicity of glutamate analogs. CS preparations were added to cultured neurons before and after the administration of glutamate analogs. Then, the extents of both neuronal cell death and survival were estimated. Pre‐administration of a highly sulfated CS preparation, CS‐E, significantly reduced neuronal cell death induced by not only NMDA but also (S)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid or kainate. Neither CS preparations other than CS‐E nor other highly sulfated polysaccharides such as heparin and dextran sulfate exerted any neuroprotective effects. NMDA‐induced current in neurons was not changed by pre‐administration of CS‐E, but the pattern of protein‐tyrosine phosphorylation was changed. In addition, the elevation of caspase 3 activity was significantly suppressed in CS‐E‐treated neurons. These results indicate that CS‐E prevents neuronal cell death mediated by various glutamate receptors, and suggest that phosphorylation‐related intracellular signals and the suppression of caspase 3 activation are implicated in neuroprotection by CS‐E.
Retinoic acid‐ and phorbol ester‐induced neuronal differentiation down‐regulates caveolin expression in GnRH neurons
Authors: D’Orlando Cristina , Guzzi Francesca , Gravati Marta , Biella Gerardo , Toselli Mauro , Meneveri Raffaella , Barisani Donatella , Parenti Marco
Published: February 2008

J. Neurochem. (2008) 104, 1577–1587.

GN11 and GT1‐7 are immortalized gonadotropin‐releasing hormone‐positive murine cell lines exhibiting the features of immature olfactory neurons and differentiated hypothalamic neurons, respectively. Using electron microscopy and biochemical assays (RT‐PCR and immunoblotting) we determined the presence of numerous caveolae invaginations and of caveolin‐1 and ‐2 mRNAs and proteins in GN11 cells, and their absence in GT1‐7 cells. The lack of caveolins in GT1‐7 cells might be due to the silencing of gene transcription caused by estrogen receptor α whose inhibitory activity in GN11 cells could be counter‐balanced by co‐expression of caveolin‐permissive estrogen receptor β. To test whether the unique expression of caveolins in GN11 cells is related to their immature state, we treated GN11 cells for 24–72 h with retinoic acid or phorbol ester. Both treatments led to neuronal differentiation of GN11 cells, as shown by emission of long neuritic processes, increased expression of growth cone‐associated protein‐43 and appearance of voltage‐gated K+ and Ca2+ channel currents. Concurrently, caveolins 1 and 2, and estrogen receptor β were down‐regulated in differentiated GN11, whereas estrogen receptor α was unaffected by differentiation. We conclude that caveolin expression in GN11 neurons is down‐regulated upon differentiation and up‐regulated by estrogen receptor β.
Short‐ and long‐term effects of (+)‐methamphetamine and (±)‐3,4‐methylenedioxymethamphetamine on monoamine and corticosterone levels in the neonatal rat following multiple days of treatment
Authors: Schaefer Tori L. , Skelton Matthew R. , Herring Nicole R. , Gudelsky Gary A. , Vorhees Charles V. , Williams Michael T.
Published: February 2008

J. Neurochem. (2008) 104, 1674–1685.

Rats treated with (±)‐3,4‐methylenedioxymethamphetamine (MDMA) or (+)‐methamphetamine (MA) neonatally exhibit long‐lasting learning impairments (i.e., after treatment on postnatal days (P)11–15 or P11–20). Although both drugs are substituted amphetamines, they each produce a unique profile of cognitive deficits (i.e., spatial vs. path integration learning and severity of deficits) which may be the result of differential early neurochemical changes. We previously showed that MA and MDMA increase corticosterone (CORT) and MDMA reduces levels of serotonin (5‐HT) 24 h after treatment on P11, however, learning deficits are seen after 5 or 10 days of drug treatment, not just 1 day. Accordingly, in the present experiment, rats were treated with MA or MDMA starting on P11 for 5 or 10 days (P11–15 or P11–20) and tissues collected on P16, P21, or P30. Five‐day MA administration dramatically increased CORT on P16, whereas MDMA did not. Both drugs decreased hippocampal 5‐HT on P16 and P21, although MDMA produced larger reductions. Ten‐day treatment with either drug increased dopamine utilization in the neostriatum on P21, whereas 5‐day treatment had no effect. No CORT or brain 5‐HT or dopamine changes were found with either drug on P30. Although the monoamine changes are transient, they may alter developing neural circuits sufficiently to permanently disrupt later learning and memory abilities.
Nonfinancial Performance Measures and Promotion‐Based Incentives
Authors: CAMPBELL DENNIS
Published: February 2008

In this paper, I examine the sensitivity of promotion and demotion decisions for lower‐level managers to financial and nonfinancial measures of their performance and investigate the extent to which the behavior of lower‐level managers reflects promotion‐based incentives. Additionally, I test for learning versus effort‐allocation effects of promotion‐based incentives. I find that promotion and demotion decisions for store managers of a major U.S.‐based fast‐food retailer (QSR) are sensitive to nonfinancial performance measures of service quality and employee retention after controlling for financial performance. The likelihood of demotion in this organization is also sensitive to nonfinancial performance on the dimension of service quality, while the probability of exit is primarily sensitive to financial performance measures rather than nonfinancial performance measures. I also find evidence that the behavior of lower‐level managers is consistent with the incentives created by the weighting of nonfinancial performance measures in promotion decisions. Managers in locations where there is a higher ex ante probability of promotion and a higher potential reward upon promotion demonstrate significantly higher levels and rates of performance improvement in service quality. Finally, consistent with promotion‐based incentives inducing both effort‐allocation and learning effects, I find that performance‐improvement rates for service quality: (1) are higher in prepromotion periods in markets where promotions occur, (2) decrease immediately after the occurrence of a promotion in the same market area, and (3) remain higher than in markets where promotions do not occur. These findings provide some of the first empirical evidence on an alternative to the explicit weighting of nonfinancial metrics in compensation contracts as a mechanism for generating improvements in nonfinancial dimensions of performance.
Eclogite facies metarodingites – phase relations in the system SiO2‐Al2O3‐Fe2O3‐FeO‐MgO‐CaO‐CO2‐H2O: an example from the Zermatt‐Saas ophiolite
Authors: LI X‐P. , RAHN M. , BUCHER K.
Published: February 2008

Eclogite facies metarodingites occur as deformed dykes in serpentinites of the Zermatt‐Saas ophiolite (Western Alps). They formed during the subduction of the Tethys oceanic lithosphere in the Early Tertiary. The metarodingites developed as a consequence of serpentinization of the oceanic mantle. Three major types of metarodingites (R1, R2 & R3) can be distinguished on the basis of their mineralogical composition. All metarodingites contain vesuvianite, chlorite and hydrogrossular in high modal amounts. In addition they contain: R1 – diopside, tremolite, clinozoisite, calcite; R2 – hydroandradite, diopside, epidote, calcite; and R3 – hydroandradite. Both garnets contain a small but persistent amount of hydrogarnet component. The different metarodingites reflect different original dyke rocks in the mantle. In each group of metarodingite, textural relations suggest that reactions adjusted the assemblages along the P–T path travelled by the ophiolite during subduction and exhumation. Reactions and phase relations derived from local textures in metarodingite can be modelled in the eight‐component system: SiO2‐Al2O3‐Fe2O3‐FeO‐MgO‐CaO‐CO2‐H2O. This permits the analysis of redox reactions in the presence of andradite garnet and epidote in many of the rocks. Within this system, the phase relations in eclogite facies metarodingites have been explored in terms of T–XCO2, T–μ(SiO2), μ(Cal)–μ(SiO2) and P–T sections. It was found that rodingite assemblages are characterized by low μ(SiO2) and low XCO2 conditions. The low SiO2 potential is externally imposed onto the rodingites by the large volume of antigorite‐forsterite serpentinites enclosing them. Moreover, μ(SiO2) decreases consistently from metarodingite R1 to R3. The low μ(SiO2) enforced by the serpentinites favours the formation of hydrogarnet and vesuvianite. Rodingite formation is commonly associated with hydrothermal alteration of oceanic lithosphere at the ocean floor, in particular to ocean floor serpentinization. Our analysis, however, suggests that the metarodingite assemblages may have formed at high‐pressure conditions in the subduction zone as a result of serpentinization of oceanic mantle by subduction zone fluids.
Atopic Dermatitis Among 2‐Year Olds; High Prevalence, but Predominantly Mild Disease—The PACT Study, Norway
Authors: Smidesang Ingeborg , Saunes Marit , Storrø Ola , Øien Torbjørn , Holmen Turid Lingaas , Johnsen Roar , Henriksen Anne Hildur
Published: February 2008

Abstract:  Atopic dermatitis is often the first and most prevalent manifestation of atopic disease in preschool children. The objectives of the present study were to determine the prevalence and severity of atopic dermatitis in 2‐year‐old children. Questionnaire data from a total population of 4784 two‐year olds and data from a clinical investigation of a sub‐sample of 390 children were obtained from a comprehensive prospective study (Prevention of Atopy among Children in Trondheim). The severity of the atopic dermatitis was scored both according to the Nottingham Eczema Severity Score and the Severity Scoring of Atopic Dermatitis. In the total population the prevalence of this disease, defined as any eczema and itchy rash was 16.5% (95% CI: 15.5–17.6). In the subsample, the corresponding prevalence was 20.6% (95% CI: 16.6–24.6) and 15.9% (95% CI: 12.3–19.5) when diagnosed by the UK Working Party’s Criteria. More than 70% of the children with UK‐diagnosed atopic dermatitis had mild disease according to both the Nottingham Eczema Severity Score and the Severity Scoring of Atopic Dermatitis. The prevalence of atopic dermatitis among 2‐year olds was high. However, more than two‐thirds of the children had mild disease, which may imply that the impact of atopic dermatitis as a risk factor for future atopic disease is limited.
Periungual Hyperpigmentation in Newborns
Authors: Iorizzo Matilde , Oranje Arnold P. , Tosti Antonella
Published: February 2008

Abstract:  Hyperpigmentation of the distal phalanx of both hands and feet is usually a prominent feature of dark‐skinned newborns, but recently it has been described also in fair‐skinned ones as a coincidental finding and classified as a transient benign disorder of infancy. We report our experience, having observed a group of at‐term newborns and a group of premature newborns. The group of premature newborns did not show any hyperpigmentation. On the contrary, 7 out of 40 fair‐skinned at‐term newborns had hyperpigmentation in the distal phalanx of the fingers which was not related to any dermatologic disorder and started to fade away after 2 years of age, i.e., longer than previously reported. The reason why some fair‐skinned newborns display this hyperpigmentation is not known. Although we can speculate that it can be reactive to maternal pigment hormones, its persistence is not completely in agreement with this possibility.
Childhood Bullous Pemphigoid in Association with Hyperimmunoglobulin E Syndrome
Authors: Erbagci Zulal
Published: February 2008

Abstract:  Bullous pemphigoid is an acquired immunobullous disorder affecting predominantly the elderly. It is very rare in children and exceptional in infants. Hyperimmunoglobulin E syndrome is a rare primary immunodeficiency characterized by a triad of high serum levels of polyclonal immunoglobulin E with peripheral eosinophilia, recurrent staphylococcal infections of the skin and lungs, and pruritic dermatitis. Variable associated features include coarse facies, cold cutaneous abscesses, and osteopenia. This report describes, to the best of my knowledge, the first instance of childhood bullous pemphigoid associated with hyperimmunoglobulin E syndrome in a 6‐month‐old boy.
Acquired Zinc Deficiency Acrodermatitis Associated with Nephrotic Syndrome
Authors: Shah Kara N. , Yan Albert C.
Published: February 2008

Abstract:  We present a child with new‐onset nephrotic syndrome, acrodermatitis, low serum zinc levels and decreased serum alkaline phosphatase. A diagnosis of acquired zinc deficiency acrodermatitis was made. Oral zinc supplementation led to rapid clinical resolution. The etiology of zinc deficiency in nephrotic syndrome remains unknown.
Progressive Macular Hypomelanosis in a 16‐Year Old
Authors: Perman Marissa , Sheth Pranav , Lucky Anne W.
Published: February 2008

Abstract:  Progressive macular hypomelanosis of the trunk is a disease of unclear etiology that often goes unrecognized in the clinical setting. We present a Caucasian adolescent girl with hypopigmented macules coalescing into patches on her trunk, initially diagnosed as tinea versicolor. Upon further evaluation, the patient was found to have progressive macular hypomelanosis that demonstrated improvement with sunlight exposure and doxycycline. We report this patient to make physicians more aware of this entity and discuss the literature.
Gerodermia Osteodysplastica/Wrinkly Skin Syndrome: Report of Three Patients and Brief Review of the Literature
Authors: Nanda Arti , Alsaleh Qasem A. , Al‐Sabah Humoud , Marzouk Emad E. , Salam Amr M. A. , Nanda Mousumee , Anim Jehoram T.
Published: February 2008

Abstract:  Gerodermia osteodysplastica and wrinkly skin syndrome are rare autosomal recessive disorders. Due to the many phenotypic similarities in these two conditions, it has been proposed that they represent the same disorder. Both conditions are well delineated in the genetic literature, but despite skin involvement being a striking feature, they are rarely reported in dermatology journals. In this report, we describe three Arab children from two consanguineous families who exhibit overlapping features of gerodermia osteodysplastica and wrinkly skin syndrome. All the patients had dysmorphic facial features, wrinkled skin more marked on the hands and feet, hyperextensible joints, intrauterine growth retardation, developmental delay, congenital dislocation of hips, and osteoporosis. Our observations also support the contention that gerodermia osteodysplastica and wrinkly skin syndrome have the same clinical spectrum; however, this needs to be confirmed at the molecular level.
A Range of Histologic Findings in Infantile Digital Fibromatosis
Authors: Grenier Nicole , Liang Christine , Capaldi Laura , Ney Amy , Lapidus Candace , Schappell Deborah , Katarincic Julia , Robinson‐Bostom Leslie
Published: February 2008

Abstract:  Infantile digital fibromatosis is a benign proliferation of myofibroblasts with characteristic eosinophilic intracytoplasmic inclusion bodies. Clinically, patients present in the first several years of life with asymptomatic, smooth, flesh‐colored nodules located on the dorsal or lateral aspect of the fingers or toes. The lesions have a tendency for spontaneous regression and recur over 60% of the time following excision. Observation is often recommended, while surgery is reserved for cases of rapid growth or functional impairment. We report three patients, ranging in age from 8 months to 8 years, with infantile digital fibromatosis. All three patients presented with nodules on the hands or feet and all shared histologic findings of spindle cells with characteristic inclusion bodies. Pathologic features ranged from a haphazard arrangement of spindle cells with few inclusion bodies and numerous lymphocytes to a well‐organized arrangement of spindle cells with abundant inclusion bodies and rare lymphocytes. All three patients underwent excision for diagnosis or treatment of their tumors with two of the patients experiencing a recurrence.
Phacomatosis Pigmentokeratotica: A Follow‐up Report Documenting Additional Cutaneous and Extracutaneous Anomalies
Authors: Del Carmen Boente María , Asial Raúl A. , Happle Rudolf
Published: February 2008

Abstract: This is a follow‐up report on a boy with phacomatosis pigmentokeratotica. At the age of 10 years he had, in addition to a sebaceous nevus and a speckled lentiginous nevus, multiple lesions of a collagen nevus localized on the chin and in the lumbar area. On the left shoulder, a small telangiectatic spot was present within the area of the speckled lentiginous nevus. Moreover, hemiatrophy of the left‐hand side of the body and hyperhidrosis of the left lumbar area were noted. At the age of 16, the lesions of his collagen nevus had considerably enlarged and showed an arrangement along Blaschko lines. Additional pinhead‐sized vascular lesions were noted, with preponderance within the area of the speckled lentiginous nevus in the left scapular region and on his left leg. Moreover, the boy had developed severe arterial hypertension since the age of 13. Angiographic examination showed an aortic stenosis that reached from the aortic arch down to the origin of the renal arteries, necessitating a surgical intervention. From this follow‐up report we conclude that phacomatosis pigmentokeratotica may be associated with other cutaneous abnormalities such as linear connective tissue nevus of the collagen type and multiple pinhead‐sized angioma‐like lesions superimposed on the speckled lentiginous nevus. The associated defects of the large vessels may belong to the component of Schimmelpenning syndrome representing one “half” of phacomatosis pigmentokeratotica, rather than being part of the speckled lentiginous syndrome that forms the other “half” of this twin‐spot phenotype.
Pharmacokinetics and Safety of Imiquimod 5% Cream in the Treatment of Molluscum Contagiosum in Children
Authors: Myhre Paula E. , Levy Moise L. , Eichenfield Lawrence F. , Kolb Vicki B. , Fielder Sandra L. , Meng Tze‐Chiang
Published: February 2008

Abstract:  Imiquimod cream 5%, a toll‐like receptor 7 agonist, induces α‐interferon upon topical application, prompting off‐label usage to treat children with molluscum contagiosum. We conducted an open‐label study to measure serum drug concentration in children aged 2–12 years with extensive molluscum contagiosum (≥10% total body surface area). Dependent on extent of subject disease and weight, one to three packets (12.5 mg imiquimod per packet) were applied per dose, three times per week for 4 weeks. Serum imiquimod and metabolite concentrations were measured at pre dose and 2, 4, and 8 hours postdose 1 and dose 12. Thirty children were screened; 22 children (64% boys; 91% white; mean age 6.2 ± 2.87 years; median involved body area treated 13.5%) were enrolled. Peak serum imiquimod concentrations following single and multiple dosing were low (<10 ng/mL). Imiquimod concentrations increased 2‐ to 3.5‐fold with multiple dosing. After single and multiple dosing, peak serum imiquimod (Pearson correlation r = 0.4989 and 0.7219, p < 0.05 both, respectively) and area under the serum concentration‐time curve values (r = 0.4989 and 0.7219, p < 0.05 both, respectively) correlated with dose normalized for body weight (mg/kg). Systemic drug levels were low after single and multiple doses of imiquimod 5% cream in children.
Toddler Wrap for Abdominal Biopsy or Excision
Authors: Cunningham Bari B. , Lyon Valerie B. , Palmer Christine M. , Wagner Annette M. , Cunningham Bari B.
Published: February 2008

Abstract:  Young children, especially toddlers, are anxious and uncooperative during skin procedures. Wrapping a sheet or blanket around the child is an effective way to restrain the child to maintain a sterile field. The wrap can be used for skin biopsies and small excisions on the midsection of the body, arms, and legs.
Bazex–Dupré–Christol Syndrome in a 1‐Year‐Old Boy and His Mother
Authors: BARCELOS ANDREZZA CAMARINHA NAPOLITANO , NICO MARCELLO MENTA SIMONSEN
Published: February 2008

Abstract:  Bazex–Dupré–Christol syndrome is a rare genodermatosis with cancer predisposition, characterized by follicular atrophoderma, multiple milia, congenital hypotrichosis, hypohidrosis and basal cell malformations that include nevoid basal cell carcinomas of early onset. We present two patients with this syndrome, a 1‐year‐old boy with diffuse scalp and eyebrows alopecia, milia papules on the face, ears, trunk, and limbs. Hypohidrosis was observed on his trunk and head. His 16‐year‐old mother had identical changes since childhood, with hair fragility, and multiple atrophic “ice pick” follicular depressions on the dorsa of her hands. She also had a basal cell carcinoma on her face. Microscopic examination of hairs from the mother revealed abnormalities such as diameter irregularities, broken shafts, trichorrexis nodosa and pili bifurcatti. Pili bifurcatti is an uncommon hair shaft dysplasia that has not before been observed in Bazex–Dupré–Christol syndrome.
Meta‐Analysis of Tacrolimus Ointment for Atopic Dermatitis in Pediatric Patients
Authors: YAN JUN , CHEN SHENG‐LI , WANG XIAO‐LIN , ZHOU WEN , WANG FENG‐SHAN
Published: February 2008

Abstract:  We evaluated the efficacy and safety of tacrolimus ointment in the treatment of the pediatric patients with atopic dermatitis. Tacrolimus ointment therapy resulted in the remission of atopic dermatitis, this effect of tacrolimus ointment strengths 0.03% and 0.1% were better than those of 1% hydrocortisone acetate and 1% pimecrolimus. Difference between the 0.03% tacrolimus group and the 0.1% tacrolimus group was not statistically significant.
A Single‐Blinded, Randomized Pilot Study to Evaluate the Effect of Exercise‐Induced Sweat on Truncal Acne
Authors: SHORT REBECCA W. , AGREDANO YOLANDA Z. , CHOI JOANNA MIMI , KIMBALL ALEXA B.
Published: February 2008

Abstract:  To assess the effect of exercise‐induced sweat on truncal acne, a prospective, single‐blinded, randomized, controlled, institution review board‐approved clinical trial was conducted on physically active males. Subjects were instructed to exercise long enough to break a sweat 5 days a week for 2 weeks. Group 1 did not exercise (n = 7), group 2 showered within 1 hour of exercise (n = 8), and group 3 waited at least 4 hours to shower after exercising (n = 8). No statistically significant differences in truncal acne were noted between (p = 0.84) nor within (p = 0.74 for group 1, 0.07 for group 2, and 0.09 for group 3) study groups at the end of the study period.
Hypothyroidism in Netherton Syndrome
Authors: GARTY BEN ZION , NIMRI REVITAL
Published: February 2008

Letters to the Editor are welcomed for publication (subject to editing). Letters must be signed by all authors, and must not exceed two pages of text including references. Letters should not duplicate material submitted or published in other journals. Prepublication proofs will not be provided.
Genetic and Experiential Antecedents of Alcoholism: A Prospective Study
Authors: Goodwin Donald W.
Published: February 2008

The present work builds on an extensively studied obstetrical cohort that includes a group of individuals, now in their midteens, who had a parent treated for alcoholism. To generate a comparable sample today would not only require a very large effort (many years and considerable expense), but might not be possible in most countries because of lack of records or restricted access to them, as well as difficulty in, locating people after long periods. Such a study is still possible in Denmark, which has a long tradition of cooperation between public officials and scientific investigators and invaluable centralized population and psychiatric registers.

Since such an opportunity may not present itself again, and since it is difficult to anticipate which avenues of investigation will be more profitable, the study is designed as a collaborative effort by investigators from a number of disciplines: psychiatric, psychological, neurologic, sociologic, biochemical, and electrophysiologic. From the enormous amount of data collected, genetic and experiential antecedents of alcoholism and associated psychopathology can be identified.
BOOK REVIEW
Authors: Davidson Charles S.
Published: February 2008

Book reviewed in this article:

Lieber CS (ed): Metabolic Aspects of Alcoholism. Baltimore, University Park Press, 1977.
Event‐Related Potentials During Visual Selective Attention in Children of Alcoholics*
Authors: van der Stelt Odin , Gunning W. Boudewijn , Snel Jan , Kok Albert
Published: February 2008

Event‐related potentials were recorded from 7‐ to 18‐year‐old children of alcoholics (COAs,n= 50) and age‐ and sex‐matched control children (n= 50) while they performed a visual selective attention task. The task was to attend selectively to stimuli with a specified color (red or blue) in an attempt to detect the occurrence of target stimuli. COAs manifested a smaller P3b amplitude to attended‐target stimuli over the parietal and occipital scalp than did the controls. A more specific analysis indicated that both the attentional relevance and the target properties of the eliciting stimulus determined the observed P3b amplitude differences between COAs and controls. In contrast, no significant group differences were observed in attention‐related earlier occurring event‐related potential components, referred to as frontal selection positivfty, selection negativity, and N2b. These results represent neurophysiological evidence that COAs suffer from deficits at a late (semantic) level of visual selective information processing that are unlikely a consequence of deficits at earlier (sensory) levels of selective processing. The findings support the notion that a reduced visual P3b amplitude in COAs represents a high‐level processing dysfunction indicating their increased vulnerability to alcoholism.
Individual Differences in the Biphasic Effects of Ethanol
Authors: Holdstock Louis , de Wit Harriet
Published: February 2008

Ethanol exerts both stimulant‐like and sedative‐like subjective and behavioral effects in humans depending on the dose, the time after ingestion and, we will argue, also on the individual taking the drug. This study assessed stimulant‐like and sedative‐like subjective and behavioral effects of ethanol during the ascending and descending limbs of the blood alcohol curve across a range of doses in nonproblem social drinkers. Forty‐nine healthy men and women, 21 to 35 years old, consumed a beverage containing placebo or ethanol (0.2, 0.4, or 0.8 g/kg) on four separate laboratory sessions, in randomized order and under double‐blind conditions. Subjective and behavioral responses were assessed before and at regular intervals for 3 hr after ingestion of the beverage. The lowest dose of ethanol (0.2 g/kg) only produced negligible subjective effects compared to placebo. The moderate dose (0.4 g/kg) increased sedative‐like effects 90 min after ethanol ingestion but did not increase ratings of stimulant effects at any time. The highest dose (0.8 g/kg) increased ratings of both stimulant‐ and sedative‐like effects during the ascending limb and produced only sedative‐like effects during the descending limb. Closer examination of the data revealed that individual differences in response to the highest dose of ethanol accounted for this unexpected pattern of results: about half of the subjects reported stimulant‐like effects on the ascending limb and sedative‐like effects on the descending limb after 0.8 g/kg ethanol, whereas the other half did not report stimulant‐like effects at any time after administration of ethanol. These results challenge the simple assumption that ethanol has biphasic subjective effects across both dose and time, and extend previous findings demonstrating individual differences in response to ethanol.
Alcohol Abuse, Alcoholism, and Damage to the Immune System—A Review
Authors: Cook Robert T.
Published: February 2008

Chronic alcohol abuse exacts a major social and medical toll in the United States and other Western countries. One of the least appreciated medical complications of alcohol abuse is altered immune regulation leading to immunodeficiency and autoimmunity. The consequences of the immunodeficiency include increased susceptibility to bacterial pneumonia, tuberculosis, and other infectious diseases. In addition, the chronic alcoholic often has circulating autoantibodies, and recent investigations indicate that the most destructive complications of alcoholism, such as liver disease and liver failure, may have a component of autoimmunity. Current research on altered cytokine balance produced by alcohol is leading to new insights on the regulation of the immune system in the chronic alcoholic. There is also recent development of exciting new techniques designed to improve or restore immune function by manipulation of cytokine balance. Although much remains to be learned, both in the abnormalities produced by alcohol and in the techniques to reverse those abnormalities, current progress reflects a rapidly improving understanding of the basic immune disorders of the alcoholic.
Carbohydrate‐Deficient Transferrin as a Marker of Change in Alcohol Intake in Men Drinking 20 to 60 g of Alcohol Per Day
Authors: Burke Valerie , Puddey Ian B. , Rakic Valentina , Swanson Nigel R. , Dimmitt Simon B. , Beilin Lawrence J. , Ching Smmon , Beilby John P.
Published: February 2008

We evaluated carbohydrate‐deficient transferrin (CDT) and γ‐glutarnyltranspeptidase (γ‐GT) as markers of alcohol intake and change in alcohol intake in white Australian men aged 20 to 63 years who regularly drank 20 to 60 g of alcohol/day (2 to 6 standard drinks), either as weekend (n = 14) or daily drinkers (n = 41). After 4 weeks of familiarization on usual alcohol intake, men were provided with low alcohol beer (24 times 375 ml cans, 0.9%, v/v, two‐weekly), and, for 4 weeks, consumed as much or as little as they wished with no additional alcohol permitted. In an alternate 4‐week period, the same amount of full‐strength beer (4.9%, v/v) was provided, whereas subjects continued their usual amount and pattern of alcohol consumption. The order of experimental conditions was randomized. Retrospective 7‐day diaries documented weekly alcohol intake during 4 weeks of familiarization and 8 weeks of intervention. Mean alcohol intake was 345 g/week of alcohol (SD 97) during familiarization. During the last 4 weeks of intervention (study weeks 8 to 12), mean alcohol intake either increased by 360 g/week (SD 138) with the switch from low to high alcohol or decreased by 328 g/week (SD 120) with the reverse. During familiarization (study weeks 1 to 4), alcohol intake was significantly related independently (R2= 0.21) to mean corpuscular volume (ρ= 0.008) and uric acid (ρ= 0.003), but not to γ‐GT (ρ= 0.22) nor CDT (p = 0.94). Change in alcohol intake was predicted independently (R2= 0.60) by change in CDT (ρ < 0.0001) and γ‐GT (ρ= 0.0003), but not by change in uric acid or mean corpuscular volume. A 10% change in CDT gave 70% sensitivity and 80% specificity to detect a change of at least 2 standard drinks/day; respective values were 68% and 0 for 10% change in γ‐GT. Results were not related to drinking pattern, smoking, age, or weight CDT, particularly when used as a continuous variable, may have a place in monitoring alcohol consumption, even in men whose alcohol intake is in the 20 to 60 g/day range.
Neuromuscular Responses to Disturbance of Balance in Children with Prenatal Exposure to Alcohol
Authors: Roebuck Tresa M. , Simmons Roger W. , Richardson Chariles , Mattson Sarah N. , Riley Eward P.
Published: February 2008

Alcohol‐exposed children display delayed motor development and impaired fine‐ and gross‐motor skills, including deficits in the maintenance of balance. In a recent study, we assessed the contribution of visual, somatosensory, and vestibular information to the ability to maintain balance. Our findings suggested that alcohol‐exposed children were overly reliant on somatosensory information and were unable to compensate by using the visual and/or vestibular systems. To understand the nature of these observed balance deficits, corrective postural reactions were examined by exposing standing subjects to rapid toe‐up movements of the support surface. Subjects for this study were alcohol‐exposed (ALC) and normal control (NC) children matched for age and sex. Postural reactions were quantified by measuring electromyographic activity of the triceps surae and anterior tibialis muscles. Analyses revealed no differences between the ALC and NC groups on short‐ and medium‐latency electromyographic responses, which are thought to be involuntary mono‐ and polysynaptic spinal reflexes, respectively. However, when compared with the NC group, the ALC group displayed increased long‐latency responses, which are thought to involve a transcortical pathway. Although we are not able to rule out the possibility of additional peripheral (e.g., vestibular) disturbance as a contributing factor to postural instability, our findings suggest that the balance deficits seen in alcohol‐exposed children are, at least in part, central in nature.
Neuropsychological Deficits in Adolescents with Fetal Alcohol Syndrome: Clinical Findings
Authors: Olson Heather Carmichael , Feldman Julie J. , Streissguth Ann P. , Sampson Paul D. , Bookstein Fred L.
Published: February 2008

Understanding the nature of cognitive deficits among adolescent patients with fetal alcohol syndrome (FAS) can direct future research on assessment and intervention. In an exploratory study, nine non‐retarded teenagers with FAS were administered tests of IQ and adaptive behavior, and neuropsychological tests presumed sensitive to alcohol effects. Their performance was compared with psychometric norms and to data from a sample of 174 adolescents with minimal or no prenatal alcohol exposure. These nonretarded FAS patients commonly showed behavior problems, decreased social competence, and poor school performance. Neuropsychological testing revealed significant deficits, although no one neuropsychological profile characterized all patients and not all tests revealed problems. Relatively intact performance was observed in procedural memory, some measures of reaction time, and some reading measures. Deficits were seen on attentional and memory tasks tapping visual‐spatial skills, short‐term auditory attention and memory, declarative learning, and cognitive flexibility and planning. Difficulties in processing speed and accuracy were also seen. Comparison with a subgroup of 52 nonalcohol‐exposed or minimally alcohol‐exposed adolescents with a similar range of IQ scores demonstrated that deficits among these FAS patients were not fully explained by a general lowering of IQ.
Natural History of Alcoholic Myopathy: A 5‐Year Study
Authors: Estruch Ramon , Sacanella Emilio , Fernandez‐Sola Joaquim , Nicolas Josep Maria , Rubin Emanuel , Urbano‐Marquez Alvaro
Published: February 2008

Chronic myopathy is a common complication of alcoholism, but its natural history has not been well described. We, therefore, studied muscle structure and function in a 5‐year study of 30 chronic alcoholics who became abstinent and 20 who relapsed, and 40 control subjects. The mean strength of the abstaining alcoholics increased from 18.6 to 23.2 kg; but, after 5 years, they were still substantially weaker than controls. In a subset who showed histological myopathy, the strength of half of the patients remained two standard deviations below that of controls. Alcoholics who relapsed tended to become progressively weaker (21.7 kg vs. 18.2 kg) and develop histological evidence of myopathy. Thus, continued alcohol abuse was generally reflected in deterioration of muscle strength and the appearance of histological injury to muscle. Importantly, almost half of the sober patients did not recover to normal levels, indicating that alcoholic myopathy is only partially reversible. We also unexpectedly found that, in some alcoholics, a substantial reduction in the amount of alcohol consumed may be as effective as complete abstinence in improving muscle strength or preventing its deterioration.
Effect of Alcohol Consumption on Adult and Aged Bone: A Histomorphometric Study of the Rat Animal Model
Authors: Sampson H. Wayne
Published: February 2008

The adult and aged skeleton exist in a time when osteoporosis and age‐related bone loss is at a maximum, and it is modified by lifestyle factors such as alcohol. To determine the effect of life‐long alcohol consumption on the adult and aged rat model, 4‐week‐old female Sprague‐Dawley rats were divided into three diet groups. Alcohol‐treated animals were fed a modified Lieber‐DeCarli diet ad libitum containing 35% ethanol‐derived calories, whereas the pair‐fed animals (weight‐matched to ethanol rats) received an isocaloric liquid diet in which maltose‐dextrin substituted calories supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Proximal tibiae were removed and prepared for histomorphometric analysis after 3, 6, 9, 12, or 18 months on the diets. Previous studies, with young animals, showed that chronic alcohol consumption during the age of bone development reduced bone volume and trabecular number in cancellous bone. The present study demonstrates that these reductions last throughout life. The rate of bone formation is reduced in alcohol‐fed animals, but most bone cell parameters are relative normal, except for wall thickness, indicating a reduced osteoblast activity.
Linkage of an Alcoholism‐Related Severity Phenotype to Chromosome 16
Authors: Foroud Tatiana , Bucholz Kathleen K. , Edenberg Howard J. , Goate Alison , Neuman Rosalind J. , Porjesz Bernice , Koller Daniel L. , Ric John , Reich Theodore , Bierut Laura J. , Cloninger C. Robert , Nurnberger John I. , Li T.‐K. , Conneally P. Michael , Tischfield Jay A. , Crowe Raymond , Hesselbrock Victor , Schuckit Marc , Begleiter Henri
Published: February 2008

There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi‐Structured Assessment for the Genetics of Alcoholism collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism‐related phenotype. A four‐class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes 3 and 4 had higher symptom endorsement probabilities than classes 1 and 2 for items reflecting severe alcohol dependence, and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met the Collaborative Study of the Genetics of Alcoholism, and >99% met ICD‐10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15 cM interval.
Activity of the Adenylyl Cyclase in Lymphocytes of Male Alcoholic Patients Is State Dependent
Authors: Szegedi Armin , Anghelescu Ion , Pauly Thorsten , Dahmen Norbert , Müller Matthias J. , Wetzel Hermann , Hiemke Christoph
Published: February 2008

A decreased basal and/or stimulated activity of the G‐protein/adenylyl cyclase (AC) system in peripheral blood cells has been proposed to represent a trait marker for alcoholism. However, AC activity may underlie state‐dependent changes, which may impair a proper interpretation of AC activity measurements. Our study examined systematically the AC activity in peripheral lymphocytes of 73 male alcohol‐dependent patients (according to DSM‐IV criteria) at three different time points of measurement during the clinical course of detoxification (day 0 = at admission, while still ethanol‐affected; day 2 = at the presumed peak of withdrawal symptoms; day E = after detoxification). Basal and stimulated (with GTPγS and forskolin) AC activities were measured. AC activities were compared to those of a control group of 44 healthy male age‐matched volunteers. As our main finding, we detected a significant decrease in AC activity from day 0 to day 2 (during withdrawal), with lowered AC activities in a vast majority of patients. This effect resolved after detoxification, as AC activities showed a significant increase from day 2 to E. No significant difference was detected between day O and E in AC activities of the patients. Compared with controls, AC activities in patients were significantly lower at day 2, but not at day O and E. Taken together, our results indicate rapid and marked state‐dependent changes of AC activities in alcohol‐dependent patients during the course of detoxification. For an adequate interpretation of AC activities in alcoholic patients, their clinical status must be taken into consideration.
Effects of Chronic Ethanol Exposure on Oxidation and NMDA‐Stimulated Neuronal Death in Primary Cortical Neuronal Cultures
Authors: John Joseph G. Rudolph , Lemasters J. , Crews Fulton T.
Published: February 2008

Excessive oxidative radical formation has been implicated in a number of neurodegenerative processes, including glirtamate‐N‐methylo‐aspartate (NMDA)‐mediated excitotoxicity. Previous studies have suggested that the formation of reactive oxygen species (ROS) during NMDA exposure is involved in triggering the excitotoxic cascade. Chronic exposure of primary neuronal cultures to ethanol has been shown to potentiate NMDA‐mediated processes, such as nitric oxide formation and excitotoxicity. It was the objective of this study to investigate the role of NMDA and ROS formation in the development of NMDA supersensitivity after chronic ethanol exposure. The fluorescent dyes dichlorofluorescein diacetate (H2DCF) and propidium iodide, which have been shown to be reliable markers for the detection of cellular oxidation and cell death, respectively, in neuronal culture preparations, were used to examine the relationship between ROS production and NMDA‐mediated neuronal death after chronic ethanol administration. Cultures treated chronically with ethanol (100 mM) for 96 hr displayed significantly less H2DCF oxidation when exposed to various concentrations of FeSO4 for 25 min. However, this decrease in intracellular oxidation did not have any apparent inhibitory effects on the amount of cell death observed 12 hr after the 25‐min exposure to FeSO4. When NMDA‐FeSO4‐mediated oxidation was examined in cultures treated chronically with ethanol, dose‐dependent increases in H2DCF oxidation were observed, but only in control‐treated cultures. This blunting of intracellular H2DCF oxidation did not attenuate the potentiation of NMDA‐mediated excitotoxicity observed after chronic ethanol exposure. These results suggest that the observed supersensitivity to NMDA is not due to increases in intracellular ROS formation and that chronic ethanol may induce neuronal factors that reduce ROS formation, but do not protect against normal death.
Effects of Chronic Moderate and Heavy Ethanol Consumption on Myocardial Recovery from Ischemia
Authors: Gibson Brian T. , Ong Joseph H. , Starnes Joseph W. , Farrar Roger P.
Published: February 2008

The purpose of this study was to determine the effects of chronic moderate and heavy ethanol consumption on myocardial ischemia/reperfusion injury. Three groups (n = 18) of 6‐month‐old female Sprague‐Dawley rats were fed a nutritionally balanced liquid diet. Control, moderate alcohol, and heavy alcohol groups consumed 0%, 20%, and 35% of their calories from ethanol, respectively. After 10 weeks of feeding, hearts were isolated and subjected to 21.5 min of ischemia alone, or 21.5 min of ischemia followed by 30 min reperfusion. Hearts were evaluated for hemodynamic characteristics and high‐energy phosphate content. Hearts from animals exposed to moderate and heavy amounts of ethanol recovered significantly less (30.61% and 29.45%, respectively) of their preischemic cardiac external work than control hearts (65.52%). Postischemic diastolic stiffness was increased ˜7‐fold, and high‐energy phosphate content, both creatine phosphate and adenosine triphosphate, decreased >25% by both chronic moderate and heavy ethanol consumption. In conclusion, both chronic moderate and heavy ethanol consumption exacerbate myocardial ischemia/reperfusion injury. The ethanol‐induced reduction in postischemic energy status may be the mechanism of increased diastolic stiffness and subsequent reduced cardiac external work.
Dietary Ethanol Does Not Accelerate Bone Loss in Ovariectomized Rats
Authors: Kidder L. S. , Turner R. T.
Published: February 2008

The abuse of alcohol is a behavior that can significantly compromise skeletal health. Because postmenopausal women are already at risk for low bone mass and osteoporotic fracture, this investigation sought to determine whether high concentrations of dietary ethanol exacerbate the bone loss associated with ovariectomy in rats, an animal model of human postmenopause. Six‐month‐old Sprague‐Dawley rats were ovariectomized or sham‐operated and randomly divided into groups fed a modified Lieber‐DeCarli liquid diet isoca‐lorically supplemented with 0%, 13%, or 35% ethanol (by daily caloric intake), for a period of 2 months. All animals were injected with fluorochromes at the start, 2 weeks, and 2 days before sacrifice to label mineralizing bone surfaces. At sacrifice, blood, uterus, and tibiae were harvested. No differences in serum calcium or cholesterol were found. Serum creatinine was also found to be unvaried, indicating this level of alcohol consumption did not compromise liver function. Dietary alcohol consumption at 35% of daily caloric intake was determined to increase tibial cortical medullary area and en‐docortical perimeter, while not affecting cortical area and periosteal perimeter. Ovariectomy significantly increased indices of bone turnover and resulted in cancellous bone loss, whereas alcohol consumption had no additional detrimental effects. This was a consistent pattern for other indices of proximal tibial architecture. In summary, this investigation has found that chronic ingestion of high concentrations of alcohol does not accentuate bone loss in ovarian hormone‐deficient adult female rats.