Supplementation with green tea and oregano extracts on productive characteristics, blood metabolites, and antioxidant status of Jersey cows during the transition period.

Plant extracts have been recognized as beneficial to human health and have been evaluated as feed additive for domestic and companion animals. This study evaluated oregano and green tea extracts fed to Jersey cows from approximately 21 d before calving to 21 d after calving on milk production, milk composition, and blood metabolites as well as investigated immunological and antioxidant attributes. Twenty-four Jersey cows with 441 ±â€¯27 kg of BW, 3.5 ±â€¯0.3 of body condition score (BCS), and 2.7 ±â€¯1.8 lactations were selected at approximately 28 d before the expected parturition date and were randomly assigned to three treatments with eight cows each: without plant extracts in diet (control - CON), addition of 10 g per day of oregano extract (OR), and addition of 5 g per day of green tea extract (GT). Feed intake, BW, BCS, blood metabolites, hemogram as well as oxidative stress biomarkers were evaluated from approximately 3 weeks prepartum to 3 weeks postpartum (transition period) while milk production and composition were evaluated during the first 3 weeks of lactation. Plant extracts did not change BW, BCS, and DM intake (DMI) throughout the transition period, but OR increased in approximately 20% total digestive nutrients and metabolizable energy intake on days 15 and 16 postpartum compared with CON. In the prepartum, OR increased in 48% platelets count compared to the CON, while GT augmented in 142% eosinophils compared with CON. Oregano extract reduced the levels of reactive species in the erythrocytes in 40% during prepartum and postpartum compared with CON, while GT reduced its levels in 24 and 29% during prepartum and postpartum, respectively, when compared with CON. In the postpartum period, OR increased in 60% the carbonylated protein content compared with CON, while GT reduced in 45% the levels of reactive species in plasma compared with CON. During the postpartum, both extracts increased in 33% the concentration of reduced glutathione when compared with CON. Moreover, GT tended to decrease feed efficiency in 11% when compared with CON; OE reduced milk pH and somatic cell count when compared with CON. In conclusion, OE and GT did not expressively affect immunological attributes in blood but reduce some oxidative stress biomarkers without compromising productive traits of Jersey cows during the transition period.

[Multiple erythema annulare centrifugum associated with knee monoarthritis revealing Capnocytophagacanimorsus infection]. / Erythème annulaire centrifuge multiple et monoarthrite révélateurs d'une infection à Capnocytophaga canimorsus.

INTRODUCTION: Capnocytophagacanimorsus (C. canimorsus), a commensal Gram-negative bacillus found in the oral cavity of dogs and cats, is pathogenic for humans, with the most common clinical manifestations being septicemia, meningitis and endocarditis. Herein we report a case of CC bacteremia manifesting as multiple plaques of erythema annulare centrifugum associated with monoarthritis of the knee. PATIENTS AND METHODS: A 66-year-old man consulted for a skin rash and monoarthritis of the right knee with fever following an insect bite on his right hallux. Cutaneous examination revealed numerous erythematous annular plaques on the trunk and limbs with centrifugal extension. Analysis of synovial fluid from the right knee showed an inflammatory liquid with a sterile bacteriological culture and PCR was negative for Borrelia. C. canimorsus bacteria were isolated from blood cultures. 16S RNA PCR performed on the synovial fluid was positive for the same organism. The patient's history revealed that his hallux wound had been licked by his dog. DISCUSSION: C. canimorsus most frequently affects immunosuppressed subjects. Cutaneous signs are seen in half of all cases, most frequently presenting as cellulitis, pathological livedo or thrombotic purpura. We report herein a case of CC bacteremia in an immunocompetent patient manifesting as multiple plaques of erythema annulare centrifugum, an unusual sign, and monoarthritis of one knee.

High-fat Diet and Physical Exercise Differentially Modulate Adult Neurogenesis in the Mouse Hypothalamus.

The hypothalamus has emerged as a novel neurogenic niche in the adult brain during the past decade. However, little is known about its regulation and the role hypothalamic neurogenesis might play in body weight and appetite control. High-fat diet (HFD) has been demonstrated to induce an inflammatory response and to alter neurogenesis in the hypothalamus and functional outcome measures, e.g. body weight. Such modulation poses similarities to what is known from adult hippocampal neurogenesis, which is highly responsive to lifestyle factors, such as nutrition or physical exercise. With the rising question of a principle of neurogenic stimulation by lifestyle in the adult brain as a physiological regulatory mechanism of central and peripheral functions, exercise is interventionally applied in obesity and metabolic syndrome conditions, promoting weight loss and improving glucose tolerance and insulin sensitivity. To investigate the potential pro-neurogenic cellular processes underlying such beneficial peripheral outcomes, we exposed adult female mice to HFD together with physical exercise and evaluated neurogenesis and inflammatory markers in the arcuate nucleus (ArcN) of the hypothalamus. We found that HFD increased neurogenesis, whereas physical exercise stimulated cell proliferation. HFD also increased the amount of microglia, which was counteracted by physical exercise. Physiologically, exercise increased food and fat intake but reduced HFD-induced body weight gain. These findings support the hypothesis that hypothalamic neurogenesis may represent a counter-regulatory mechanism in response to environmental or physiological insults to maintain energy balance.

Electro-cortical correlates of multisensory integration using ecologically valid emotional stimuli: Differential effects for fear and disgust.

Multisensory integration (MSI) is crucial for human communication and social interaction and has been investigated in healthy populations and neurodevelopmental disorders. However, the use of stimuli with high ecological validity is sparse, especially in event-related potential (ERP) studies. The present study examined the ERP correlates of MSI in healthy adults using short (500 ms) ecologically valid professional actor-produced emotions of fear or disgust as vocal exclamation or facial expression (unimodal conditions) or both (bimodal condition). Behaviourally, our results show a general visual dominance effect (similarly fast responses following bimodal and visual stimuli) and an MSI-related speedup of responses only for fear. Electrophysiologically, both P100 and N170 showed MSI-related amplitude increases only following fear, but not disgust stimuli. Our results show for the first time that the known differential neural processing of fear and disgust also holds for the integration of dynamic auditory and visual information.

Sorafenib treatment for recurrent hepatocellular carcinoma after liver transplantation.

BACKGROUND: With an increasing number of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (OLT), HCC recurrence remains the main limiting factor for long-term survival. We herein report our experience with sorafenib treatment for HCC recurrence post-OLT. PATIENTS AND METHODS: We reviewed data on transplanted HCC patients receiving sorafenib for HCC recurrence. RESULTS: Fourteen patients were included for the period November 2006 to February 2011. There were 9 men and 5 women of median age of 57 years. Twelve patients (86%) received rescue grafts through Eurotransplant allocation. Median values for alpha fetoprotein levels, Model for End-Stage Liver Disease score, sorafenib daily dose, and length of treatment were 97 ng/mL, 10, 400 mg, and 6.5 months, respectively. Sorafenib side effects led to discontinuation (n = 4) or reduction (n = 2) of the daily dose. Four patients experienced tumor progression during treatment. Seven patients are currently alive, 3 patients died of tumor progression, and 4 patients of non-tumor-related causes of death. Median survival was 25 months. CONCLUSION: Sorafenib treatment for HCC recurrence in transplant recipients represents a challenging oncologic approach that requires further validation in prospective, multicenter studies.

Dietary supplementation of conjugated linoleic acid in horses increases plasma conjugated linoleic acid and decreases plasma arachidonic acid but does not alter body fat.

Studies using dietary supplementation of eicosapentaenoic and docosahexaenoic fatty acids (FA) in horses report inconsistent anti-inflammatory results but consistently report an increase in plasma arachidonic acid (C20:4), the major substrate of cyclooxygenase (COX) II inflammatory pathway. Conjugated linoleic acid has shown anti-inflammatory effects in laboratory and food animal species, but effects of CLA supplementation in horses have not been reported. Our objective was to determine the effects of CLA supplementation on plasma CLA and C20:4 and body fat in healthy horses at maintenance. In a crossover study, 12 mature mares were blocked by breed, age, and BCS and separated into 2 treatment groups (n = 6/group). Groups were fed CLA and corn oil (CO; isocaloric control) for two 6-wk feeding periods, separated by a 4-wk period during which treatment was withheld. Corn oil or CLA supplement (55% mixed CLA isomers) was incorporated into diets at 0.01% BW/d. Mares were fed individually and restricted to dry lots to control forage intake. Rump fat thickness (RFT), BW, and BCS were measured before (d 0) and after (d 42) each feeding period. Blood was collected on d 0, 14, 28, and 42 of each 6-wk period for GLC analysis of plasma CLA isomers (cis-9, trans-11; trans-10, cis-12; and trans-9, trans-11) and C20:4. An ANOVA was conducted to compare the response of RFT, BW, and BCS of CLA-treated and control mares. A mixed methods analysis with repeated measures was used to detect differences in plasma FA concentrations. There were no differences in BW, RFT, or BCS between treatment groups. All CLA isomers present in the CLA supplement were greater in plasma of horses fed CLA compared with controls (P < 0.01). Additionally, plasma concentrations of C20:4 were decreased in horses fed CLA (P < 0.05). This decline in C20:4 may impact the COX II pathway and warrants further investigation. These results suggest that in an equine model, dietary CLA increases circulating concentrations of supplemented CLA isomers and decreases circulating C20:4. Examining physiological effects of CLA supplementation in horses at varying levels of growth, exercise, and progression of joint disease may offer insight to potential benefits of CLA in the horse.

Docosahexaenoic acid elevates trans-18:1 isomers but is not directly converted into trans-18:1 isomers in ruminal batch cultures.

Pathways of docosahexaenoic (DHA) biohydrogenation are not known; however, DHA is metabolized by ruminal microorganisms. The addition of DHA to the rumen alters the fatty acid profile of the rumen and milk and leads to increased trans-18:1 isomers, particularly trans-11 18:1. This study included 2 in vitro experiments to identify if the increase in trans-11 C18:1 was due to DHA being converted into trans-11 18:1 or if DHA stimulated trans-11 products from biohydrogenation of other fatty acids. In each experiment, ruminal microorganisms collected from a lactating Holstein cow were incubated in 10-mL batch cultures for 0, 6, 24, and 48 h and a uniformly (13)C-labeled DHA was added to the cultures at 0 h as a metabolic tracer. Experiment 1 tested 0.5% DHA supplementation and experiment 2 examined 1, 2, and 3% DHA supplementation to determine if the level of DHA effected its conversion into trans-11 18:1. In both experiments, any fatty acid that was enriched with the (13)C label was determined to arise from DHA. Palmitic (C16:0), stearic (C18:0), all trans-18:1, eicosanoic (C20:0), and docosanoic (C22:0) acids were examined for enrichment. In experiment 1, the amount of trans-18:1 isomers increased 0.415 mg from 0 to 48 h; however, no label was found in trans-18:1 at any time. Docosanoic acid was highly enriched at 24h and 48 h to 20.2 and 16.3%. Low levels of enrichment were found in palmitic and stearic acids. In experiment 2, trans-18:1 isomers increased 185, 256, and 272% from 0 to 48 h when DHA was supplemented at 1, 2, and 3%, respectively; however, as in experiment 1, no enrichment occurred of any trans-18:1 isomer. In experiment 2, low levels of label were found in palmitic and stearic acids. Enrichment of docosanoic acid decreased linearly with increased DHA supplementation. These studies showed that trans-18:1 fatty acids are not produced from DHA, supporting that DHA elevates trans-18:1 by modifying biohydrogenation pathways of other polyunsaturated fatty acids.

Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism.

OBJECTIVES: To study the frequency of different gene mutations in patients with early-onset parkinsonism and bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and the short- and long-term surgical outcome in mutation-positive (MUT+) and -negative (MUT-) patients. METHODS: Eighty patients with disease onset at age

Evaluation of the immediate and midterm effects of mobilization in hot spa water on static and dynamic balance in elderly subjects.

OBJECTIVES: The purpose of this study was to compare one and four weeks of active mobilization during balneotherapy (B) with mobilization on land (L) in terms of the respective effects on static and dynamic balance in elderly subjects. METHODS: Twelve elderly volunteers (mean age: 65.6+/-6.3 years) were evaluated for pain (on a visual analogue scale, [VAS]), static balance (as measured by the centre of foot pressure, [COP]) and dynamic balance (the "Timed Up and Go" [TUG] test). Six measurement sessions were performed: three baseline sessions before exercise sessions (PostL, PreB1 and PreB4) and then after a land-based session L and after one and four weeks (B1 and B4) of balneotherapy at 34 degrees C (PostL, PostB1 and PostB4, respectively). RESULTS: A Friedman analysis of variance (ANOVA) revealed significant differences between the six conditions in terms of the TUG and VAS results (p<0.01 and p<0.05, respectively). The TUG time decreased after the balneotherapy session(s) (p<0.01, PreB1 versus PostB1 and PreB4 versus PostB4). After sessions B1 and B4, a decrease in the VAS score was noted (p<0.05, PreB1 versus PostB1 and PreB4 versus PostB4). In contrast, there were no significant postbalneotherapy changes in any of the postural parameters. CONCLUSION: Balneotherapy sessions appear to induce a decrease in pain and an increase in dynamic mobility. This might be explained by enhanced proprioceptive input during neuromuscular mobilization in water (i.e. with increased resistance but a lower load).

Generation and characterisation of monoclonal antibodies to oleanolic acid.

Monoclonal antibodies to oleanolic acid, a pentacyclic triterpene, were generated using the hybridoma fusion method described by Kohler and Milstein . Protein conjugates of the target molecule for immunisation were prepared either by directly linking the isoprenoid to different protein carriers via the carboxylic function or after introduction of a succinic spacer between the protein carrier and position 3 of the target molecule. Antibodies of three different cell lines were further analysed by competitive ELISA and were shown to be directed either against both rings A and B or to ring E of the pentacyclic system. Thus these antibodies can be used in the specific detection of oleanolic acid itself or of a broad range of oleanolic acid derivatives sharing a specific structural moiety. Therefore these antibodies may be interesting tools for the screening of putative terpenoid-containing plants.

Tumor necrosis factor-alpha-induced adipose-related protein (TIARP), a cell-surface protein that is highly induced by tumor necrosis factor-alpha and adipose conversion.

Tumor necrosis factor-alpha (TNF alpha) is involved in the physiological and biological abnormalities found in two opposite metabolic situations: cachexia and obesity. In an attempt to identify novel genes and proteins that could mediate the effects of TNFalpha on adipocyte metabolism and development, we have used a differential display technique comparing 3T3-L1 cells exposed or not to the cytokine. We have isolated a novel adipose cDNA encoding a TNF alpha-inducible 470-amino acid protein termed TIARP, with six putative transmembrane regions flanked by a large amino-terminal and a short carboxyl-terminal domain, a structure reminiscent of channel and transporter proteins. Commitment into the differentiation process is required for cytokine responsiveness. The differentiation process per se is accompanied by a sharp emergence of TIARP mRNA transcripts, in parallel with the expression of the protein at the plasma membrane. Transcripts are present at high levels in white and brown adipose tissues, and are also detectable in liver, kidney, heart, and skeletal muscle. Whereas the biological function of TIARP is presently unknown, its pattern of expression during adipose conversion and in response to TNF alpha exposure as a transmembrane protein mainly located at the cell surface suggest that TIARP might participate in adipocyte development and metabolism and mediate some TNF alpha effects on the fat cell as a channel or a transporter.

From food to nutritional support to specific nutraceuticals: a journey across time in the treatment of disease.

Hospitalized patients who are unable to eat or cannot eat enough to meet their metabolic needs are given parenteral or enteral nutritional support. This form of therapy is now also given to patients at home. Nutritional support is a recent development, prior to which the value of food was recognized for its medicinal benefits as nutraceuticals. The value of such "alternative" therapy is now being rediscovered by many patients who enhance their dietary intake with these traditional remedies. In Western culture, conventional medicine until recently has largely rejected the use of such "alternative" therapeutic intervention. Based on an increasing database, though, insight has been gained concerning the scientific validity of many previously termed established nutraceuticals. We focus here on the effects of honey, green tea, ginseng, and vitamin supplementation on the immune system. Honey has proven antimicrobial activity. Green tea enhances humoral and cell-mediated immunity while decreasing the risk of certain cancers and the risk of cardiovascular disease. Ginseng enhances production of macrophages, B and T cells, natural killer cells, and colony-forming activity of bone marrow. Vitamin supplementation is associated with increased antibody titer response to both hepatitis B and tetanus vaccines as a result of macrophage and T cell stimulation. Because of these findings, nutraceuticals are becoming more widely accepted as an adjunct to conventional therapies for enhancing general well-being.

Pharmacological activity and membrane interactions of antiarrhythmics: 4D-QSAR/QSPR analysis.

PURPOSE: This study was done to explore the relationships of both macroscopic and molecular level physicochemical properties to in-vivo antiarrhythmic activity and interactions with phospholipid membranes for a set of cationic-amphiphilic analogs. METHODS: The 4D-QSAR method, recently developed by Hopfinger and co-workers (1), was employed to establish 3D-QSAR/QSPR models. Molecular dynamics simulations provided the set of conformational ensembles which were analyzed using partial least squares regression in combination with the Genetic Function Approximation algorithm to construct QSAR and QSPR models. RESULTS: Significant QSAR models for in-vivo antiarrhythmic activity were constructed in which logP (the partition coefficient), and specific grid cell occupancy (spatial) descriptors are the main activity correlates. LogP is the most significant QSAR descriptor. 4D-QSPR models were also developed for two analog-membrane interaction properties, the change in a membrane transition temperature and the ability of the analogs to displace adsorbed Ca(2+)-ions from phosphatidylserine monolayers. CONCLUSIONS: Spatial features, represented by grid cell occupancy descriptors, supplement partition coefficient, which is the most important determinant of in-vivo antiarrhythmic activity, to provide a comprehensive model for drug action. The QSPR models are less significant in statistical measures, and limited to interpretation of possible molecular mechanisms of action.

The postimperative negative variation following ambiguous matching of auditory stimuli.

Previous studies using the delayed-matching-to-sample paradigm with visual stimuli reliably induced a postimperative negative variation (PINV) in both schizophrenic patients and healthy controls. The PINV was found to be: (a) larger in schizophrenic patients than controls; (b) larger under conditions of ambiguous as compared to clear matching conditions; and (c) larger over right-hemispheric, fronto-temporal regions in controls, while a less asymmetrical distribution with a tendency for left-frontal predominance occurred in schizophrenic patients. The present study examined to what extent the development and scalp distribution of the PINV were modality-specific by applying the delayed-matching-to-sample design using auditory stimuli. Furthermore, the neurophysiological state during anticipatory negativity (CNV) and PINV was examined by presenting acoustic probe stimuli (one per trial on 50% of the trials) during baseline, CNV or PINV interval. Event-related slow and probe-evoked potentials were recorded in 13 patients with a chronic schizophrenic disorder (DSM-III-R) and 13 healthy control Ss from 15 electrode sites including midline and two sagittal rows over each hemisphere. Comparable group differences and effects of ambiguity on PINV amplitudes were found for both modalities, visual and auditory. The auditory stimuli produced a fronto-central distribution of the PINV in both groups. The probe-evoked vertexpotential was smaller in patients compared to controls, but exhibited comparable modulation with the largest amplitude during the CNV in both groups. Results suggest modality-non-specific cognitive determinants of the PINV. However, stimulus modality did affect the scalp distribution of the PINV. Probe-evoked responses point to different functional meaning of negativities prior to (CNV) and following (PINV) task-relevant stimuli.

The impact of performance uncertainty on the postimperative negative variation.

In a delayed matching-to-sample task, the impact of clear or ambiguous go versus clear no-go signals on the post-imperative negative variation (PINV) was examined in 11 patients with a chronic schizophrenic disorder (DSM-III-R) and in a control group of 13 healthy subjects matched to the patient sample by age, sex, and education. Size and spatial position of a visual S2 had to be matched to one of two visual patterns in the S1 presented 4 s earlier. In 96 trials, the S2 was identical in size with one of the two patterns of S1 (clear matching). These trials varied pseudorandomly, with 60 trials in which the S2 was of intermediate size. On a randomly interspersed additional 48 trials, an S2 differing in color and shape signaled no-go. The electroencephalogram was recorded from Fz, Cz, Pz, F3, F4, C3, C4, P3, and P4. Although groups did not differ in contingent negative variation amplitude, the PINV was generally more pronounced in patients than in controls. In both groups, ambiguity of the to-be-matched S2 produced larger PINV amplitudes; the no-go signal elicited only a small PINV. Differential effects of ambiguity and no-go on PINV amplitude and its scalp distribution suggest that "performance" and "action" uncertainty contribute to PINV generation and that thresholds for both effects are reduced in schizophrenics.

A model for the evaluation of mandibular bone response to implant materials.

An in vivo animal (goat) mandibular bone model has been evaluated for the cortical and trabecular bone response to biomaterials with different elastic modulus and/or different surfaces. The effect of the elastic modulus on the bone formation was also studied. The difficulties encountered in orientation of the implants probably could have been surmounted if pre-operative radiographs had been available. It was also established that there is a large variance in the amount of trabecular and cortical bone in the mandible of the goat 'bone model'.

Carbonate petrography, kerogen distribution, and carbon and oxygen isotope variations in an early Proterozoic transition from limestone to iron-formation deposition, Transvaal Supergroup, South Africa.

The transition zone comprises Campbellrand microbialaminated (replacing "cryptalgalaminate") limestone and shale, with minor dolomite, conformably overlain by the Kuruman Iron Formation of which the basal part is characterized by siderite-rich microbanded iron-formation with minor magnetite and some hematite-containing units. The iron-formation contains subordinate intraclastic and microbialaminated siderite mesobands and was deposited in deeper water than the limestones. The sequence is virtually unaltered with diagenetic mineral assemblages reflecting a temperature interval of about 110 degrees to 170 degrees C and pressures of 2 kbars. Carbonate minerals in the different rock types are represented by primary micritic precipitates (now recrystallized to microsparite), early precompactional sparry cements and concretions, deep burial limpid euhedral sparites, and spar cements precipitated from metamorphic fluids in close contact with diabase sills. Paragenetic pathways of the carbonate minerals are broadly similar in all lithofacies with kerogen intimately associated with them. Kerogen occurs as pigmentation in carbonate crystals, as reworked organic detritus in clastic-textured carbonate units, and as segregations of kerogen pigment around late diagenetic carbonate crystals. Locally kerogen may also be replaced by carbonate spar. Carbon isotope compositions of the carbonate minerals and kerogen are dependent on their mode of occurrence and on the composition of the dominant carbonate species in a specific lithofacies. Integration of sedimentary, petrographic, geochemical, and isotopic results makes it possible to distinguish between depositional, early diagenetic, deep burial, and metamorphic effects on the isotopic compositions of the carbonate minerals and the kerogen in the sequence. Major conclusions are that deep burial thermal decarboxylation led to 13C depletion in euhedral ferroan sparites and 13C enrichment in kerogen (organic carbon). Metamorphic sparites are most depleted in 13C. Carbonates in oxide-rich iron-formations are more depleted in 13C than those in siderite-rich iron-formation whereas the kerogens in oxide banded iron-formations (BIF) are more enriched. This implies that the siderite-rich iron-formations were not derived from oxide-rich iron-formation through reduction of ferric iron by organic matter. Organic matter oxidation by ferric iron did, however, decrease the abundance of kerogen in oxide-rich iron-formation and led to the formation of isotopically very light sparry carbonates. Siderite and calcmicrosparite both represent recrystallized primary micritic precipitates but differ in their 13C composition, with the siderites depleted in 13C by 4.6 per mil on average relative to calcmicrosparite. This means that the siderites were precipitated from water with dissolved inorganic carbon depleted in 13C by about 9 per mil relative to that from which the limestones precipitated. This implies an ocean system stratified with regard to total carbonate, with the deeper water, from which siderite-rich iron-formation formed, depleted in 13C. Iron-formations were deposited in areas of very low organic matter supply. Depletion of 13C may, therefore, derive not from degradation of organic matter but from hydrothermal activity, a conclusion which is supported by 18O composition of the carbonate minerals and trace element and rare earth element (REE) compositions of the iron-formations.

Impaired maturation of Purkinje cells in the fetal alcohol syndrome of the rat. Light and electron microscopic investigations.

Alcohol was administered in a vitamin-supplemented liquid diet (Stardit) to Wistar rats 4 weeks before mating and during pregnancy. Of the daily calories 38--40% were supplied by alcohol and by isocaloric sucrose in the controls. Offspring of alcohol drinking dams showed a reduced birth weight and gained weight less rapidly than the controls. On day 3, 4, 7, 12, 17 and 21, experimental animals and controls were perfused for histological and electron microscopic investigations. Morphometric analysis of the cerebella (Fol. 5 and Fol. 8) showed no difference in the number of Purkinje cells. However, on day 7 the Purkinje cell nuclei of experimental pups were significantly smaller. This difference disappeared at day 12. Electron microscopic investigations in the 4, 7, and 12 days old experimental animals revealed a delayed cytoplasmic maturation of Purkinje cells which mainly involved the rough endoplasmic reticulum. At 17 days, there was no difference between the two groups. These data are discussed in relation to alcohol-induced metabolic changes in the brain.