Serotonin transporter (5-HTTLPR) genotypes and trinucleotide repeats of androgen receptor exert a combinatorial effect on hormonal milieu in patients with lifelong premature ejaculation.

Premature ejaculation is one of the most common sexual disorders in men due to uncontrolled modulation of spinal reflexes controlled by cortico-limbic centers in the brain. In this study, we investigate the combinatorial effects of trinucleotide repeats of androgen receptor and allelic variants of the 5-HTTLPR gene on sex steroids, hypophyseal hormones, sexual performance, and premature ejaculation assessment parameters among evidence-based lifelong premature ejaculation subjects. A total of 271 outpatients (age 26.6 ± 1.9) consulting for evidence-based lifelong premature ejaculatory dysfunction were selected in this study. The control group consists of 155 men with normal IELT (>4 min). The study revealed that the subjects who have the highest (≥26) CAG stretches depicted a significantly higher serum oxytocin levels (102.1 pg/ml; n = 126, p < 0.001) compared with the control group (71.2 pg/ml; n = 75, p = <0.001) and patients which have medium (22-25) and short (≤21) CAG stretches (76.63 ng/ml; n = 64, p < 0.001 vs. 77.4 ng/ml; n = 81, p < 0.001). Almost 33 (26.1%) lifelong premature ejaculatory patients had AR variant of longer (≥26) CAG repeats was homozygous for S alleles (SS), 45 (35.7%) was homozygous for L allele (LL), and 48 (38%) had the L/S or S/L genotype of 5-HTTLPR gene. Homozygous (SS) alleles have a significant positive correlation (r = 0.44, p < 0.0001) with the high score of BDI-II (39.1, n = 126, p < 0.001). However, LL alleles have shown a significant positive correlation with PEDT (r = 0.46, p < 0.001) and negative correlation with self-estimated IELT and intercourse satisfaction (r = -0.35, p < 0.001). The innovative study design elaborates that androgen receptor trinucleotide repeats and 5-HTTLPR genotypes have combinatorial impact on hormonal milieu and sexual function regarding evidence-based lifelong premature ejaculatory dysfunction patients.

Primary Spinal Epidural Lymphoma As a Cause of Spontaneous Spinal Anterior Syndrome: A Case Report and Literature Review.

Background Primary spinal epidural lymphoma (PSEL) is one of the rarest categories of tumors. Spinal cord compression is an uncommon primary manifestation and requires to be treated with surgery for the purpose of diagnosis and decompression. Case Presentation A 45-year-old man presented with a new onset thoracic pain and progress to an anterior spinal syndrome with hypoesthesia and loss of thermalgesia. Magnetic resonance image showed a paravertebral mass that produces medullary compression at T3. The patient was taken up to surgery, where the pathology examination showed a diffuse large B-cell lymphoma. Conclusions PSEL is a pathological entity, which must be considered on a middle-aged man who began with radicular compression, and the treatment of choice is decompression and biopsy. The specific management has not been established yet, but the literature suggests chemotherapy and radiotherapy; however, the outcome is unclear.

Effect of foods and Mediterranean diet during pregnancy and first years of life on wheezing, rhinitis and dermatitis in preschoolers.

BACKGROUND: There is a conflictive position if some foods and Mediterranean diet (MedDiet) consumed by the mother during pregnancy and by the child during the first years of life can be protective for current wheezing, rhinitis and dermatitis at preschool age. METHODS: Questionnaires of epidemiological factors and food intake by the mother during pregnancy and later by the child were filled in by parents in two surveys at two different time points (1.5 yrs and 4 yrs of life) in 1000 preschoolers. RESULTS: The prevalences of current wheezing, rhinitis and dermatitis were 18.8%, 10.4%, and 17.2%, respectively. After multiple logistic analysis children who were low fruit consumers (never/occasionally) and high fast-food consumers (≥3 times/week) had a higher risk for current wheezing; while intermediate consumption of meat (1 or 2 times/week) and low of pasta by mothers in pregnancy were protected. For current rhinitis, low fruit consumer children were at higher risk; while those consuming meat <3 times/week were protected. For current dermatitis, high fast food consumption by mothers in pregnancy; and low or high consumption of fruit, and high of potatoes in children were associated to higher prevalence. Children consuming fast food >1 times/week were protected for dermatitis. MedDiet adherence by mother and child did not remain a protective factor for any outcome. CONCLUSION: Low consumption of fruits and high of meat by the child, and high consumption of potatoes and pasta by the mother had a negative effect on wheezing, rhinitis or dermatitis; while fast food consumption was inconsistent.

Analysis of FOXP3 gene in children with allergy and autoimmune diseases.

BACKGROUND: Allergy and autoimmunity are important immunological entities underlying chronic diseases in children. In some cases both entities develop simultaneously in the same patient. FOXP3 gene codes for a transcription factor involved in regulation of the immune system. Considering that regulatory T cells are involved in controlling immunological disease development, and the relevant role of FOXP3 in this kind of T cells, the objective of this study was to analyse the FOXP3 gene in the most prevalent autoimmune diseases and/or allergies in childhood in a European population. METHODS: A total of 255 Caucasian individuals, 95 controls and 160 patients diagnosed with allergic, autoimmune or both diseases were included in this study. The molecular analysis of FOXP3 was performed by DNA sequencing following the recommendations for quality of the European Molecular Genetics Quality Network. Genomic DNA was extracted from peripheral blood of all participants and was amplified using the polymerase chain reaction. After the visualisation of the amplified fragments by agarose gel-electrophoresis, they were sequenced. RESULTS: Thirteen different polymorphisms in FOXP3 gene were found, seven of which had not been previously described. The mutated allele of SNP 7340C>T was observed more frequently in the group of male children suffering from both allergic and autoimmune diseases simultaneously (p=0.004, OR=16.2 [1.34-195.15]). CONCLUSIONS: In this study we identified for first time genetic variants of FOXP3 that are significantly more frequent in children who share allergic and autoimmune diseases. These variants mainly affect regulatory sequences that could alter the expression levels of FOXP3 modifying its function including its role in Treg cells.

Maternal nutrition during pregnancy and risk of asthma, wheeze, and atopic diseases during childhood: a systematic review and meta-analysis.

BACKGROUND: Epidemiologic studies suggest a relationship between maternal nutrition during pregnancy and the occurrence of asthma and atopic conditions during childhood. However, individual study results are conflicting. The objective of this meta-analysis was to critically examine the current evidence for an association between nutrition (dietary patterns, food groups, vitamins, or oligo-elements) ingestion during pregnancy and asthma, wheeze, or atopic conditions in childhood. METHODS: The inclusion criteria were as follows: (i) systematic recording of diet during the gestational period and (ii) documentation of asthma, wheezing, eczema, or other atopic disease in the offspring. The primary outcomes were prevalence of asthma or wheeze among the offspring during childhood; and secondary outcomes were prevalence of eczema, allergic rhinitis, or other atopic conditions. RESULTS: We found 120 titles, abstracts, and citations, and 32 studies (29 cohorts) were included in this analysis. Data on vitamins, oligo-elements, food groups, and dietary patterns during pregnancy were collected. A meta-analysis revealed that higher maternal intake of vitamin D [odds ratio (OR) = 0.58, 95% confidence interval (CI) = 0.38-0.88], vitamin E (OR = 0.6, 95% CI = 0.46-0.78), and zinc (OR = 0.62, 95% CI = 0.40-0.97) was associated with lower odds of wheeze during childhood. However, none of these or other nutrients was consistently associated with asthma per se or other atopic conditions. CONCLUSIONS: Current evidence suggests a protective effect of maternal intake of each of three vitamins or nutrients (vitamin D, vitamin E, and zinc) against childhood wheeze but is inconclusive for an effect on asthma or other atopic conditions.

Epilepsia postraumática, evaluación de los criterios de causalidad. A propósito de un caso / Posttraumatic epilepsy and its differential diagnosis in impairment evaluation. Case report

Objetivo: Se presenta un caso de valoración pericial de nexo de causalidad en una epilepsia postraumática, entre un traumatismo craneoencefálico (TCE) ocurrido cuatro años antes y una agresión con resultado de lesiones leves, en un varón de 21 años, consumidor ocasional de alcohol, cannabis y cocaína. El objetivo de este artículo es el análisis de los criterios médico-legales aplicables al caso y la correcta evaluación del estado anterior del paciente. La valoración pericial resulta afectada por la complejidad de los mecanismos desencadenados en el TCE, por la intervención de otros factores que pueden contribuir a la aparición de epilepsia, y por la existencia de una extensa literatura sobre el tema, en muchos casos con hallazgos dispares y contradictorios. Conclusiones: En el presente caso, evaluados los criterios de causalidad, la epilepsia se considera secundaria al TCE sufrido cuatro años antes (AU)

Introduction: This report shows a case of posttraumatic epilepsy related to head injury four years ago and aggression with result in mild injury, in a 21-year-old male, alcohol, cannabis and cocaine user. The aim of this report is to review the expert evaluation of the link between head injury or aggression and posttraumatic epilepsy by the analysis of the causal relationship factors and the influence of previously existing pathology. The expert evaluation is awkward and difficult to deal with, because of the different mechanisms of Traumatic Brain Injury (TBI) and other factors that could lead to epilepsy. Also the extensive bibliography on the subject is controversial. Conclusions: In this case the posttraumatic epilepsy can be reasonably linked to the TBI that had been undergone 4 years ago (AU)

Study of the long-term carcinogenicity potential of D-003, a mixture of high molecular weight sugarcane wax acids, in mice.

D-003, a mixture of high aliphatic primary acids purified from sugar cane wax, has shown cholesterol-lowering, anti-platelet and antioxidant effects. Previous data demonstrated that D-003 was not toxic or carcinogenic when given orally to Sprague-Dawley rats up to 1500 mg/kg. This study investigated the potential long-term oral carcinogenicity of D-003 in a second rodent species. OF1 mice of both sexes were randomized into 4 groups treated for 18 months: a vehicle control group and three groups treated with D-003 at 50, 500 and 1500 mg/kg, respectively, orally gavaged 6 days per week. Mortality, clinical symptoms, weight gain, food consumption, organ weight, blood indicators and tumour incidence did not show significant differences between control and treated groups. D-003 did not increase the frequency of neoplastic or non-neoplastic lesions with respect to the controls. Lesions observed in the study were consistent with spontaneous lesions reported for this specie. It can be concluded that D-003 did not result toxic or carcinogenic when given orally to OF1 mice for 18 months and that the highest dose was a NOAEL, consistent with results of the oral carcinogenicity study of D-003 in rats.

[Multicentric inflammatory pseudotumor with asynchronic presentation in meninges, liver, spleen and lymph nodes in a patient with seronegative spondiloarthropathy. Case report and review of the literature]. / Pseudotumor inflamatorio multicéntrico con presentación asincrónica en meninges, hígado, bazo y ganglios linfáticos en una paciente con espondiloartropatía seronegativa. Presentación de un caso y revisión de la bibliografía.

INTRODUCTION: Inflammatory pseudotumor is a reactive process in which the etiology and pathogenesis are not well defined, that can be found in any location. The cases with central nervous system affection have been described in meninges, brain, choroid plexus and cranial and spinal nerves. Multicentric cases, synchronous and asynchronous have been described. CASE REPORT: A 45 years-old woman with a rheumatologic disease (a seronegative spondiloarthropathy) who developed an inflammatory pseudotumor in spleen, liver and abdominal lymph nodes in 1995, associated to fever of unknown origin, six years later she presented with an inflammatory pseudotumor of the meninges in the convexity of the right frontoparietal region, with fever, malaise, and increase of globular sedimentation rate, microcytic hypochromic anemia and thrombocytosis. CONCLUSION: The clinicopathologic features of this lesion are revised, including the different theories in regard to the etiology and pathogenesis, and the role of cytokines produced by inflammatory cells in the tumor.

The evaluation of the air quality impact of an incinerator by using MM5-CMAQ-EMIMO modeling system: North of Spain case study.

The use of sophisticated air pollution modeling systems to evaluate the impact of different industrial plant emissions is currently done in an extensive way. MM5-CMAQ (PSU/NCAR and EPA, USA) is one of the most applicable air quality modeling systems to evaluate those impacts. In this contribution we present the methodology and results obtained when applying the MM5-CMAQ air quality modeling system for evaluating the potential impact of an incinerator in San Sebastián (Basque Country, Spain). We have used the EMIMO (UPM, Spain) emission model to simulate the emissions from biogenic and anthropogenic sources including traffic and tertiary sector sources. The study includes the air quality impact of a highway located near the incinerator named A8 and 6 industrial plants which already exist. The impact study has been compared with the results obtained from this highway impact and the 6 industrial plants which are normally operating during the last 30 years. The system has been prepared to simulate also Cadmium, Arsenic, Nickel, Lead and Benzo(a)pyrene air quality impacts. The PCDD/F air concentrations have been determined for the 16 toxic dioxins and furans as determined in the bibliography. The criteria pollutants such as CO, NOx, SO(2), PM(10) and O(3) have also been determined according to the different EU Directives which limit the values of such a pollutants for different periods of time.

Long-term carcinogenicity of D-003, a mixture of high molecular weight acids from sugarcane wax, in Sprague Dawley rats: a 24 months study.

D-003 is a mixture of high molecular weight sugarcane wax aliphatic primary acids with cholesterol-lowering, anti-platelet and antioxidant effects. This study investigated the long-term oral toxicity and carcinogenicity of D-003 in Sprague Dawley rats of both sexes, randomly distributed into four groups: a control group, treated only with the vehicle, and three treated with D-003 (50, 500 and 1500 mg/kg). All treatments were given orally for 24 months. Mortality (survival analysis), clinical symptoms, weight gain, food consumption, organ weights, time-to-tumour or tumour incidence data were not shown between group differences or trends. With the exception of serum cholesterol levels, lower in D-003-treated groups (500 and 1500 mg/kg) than in the controls, no other difference in blood indicators was found. D-003 did not increase the frequency of neoplastic and non-neoplastic lesions compared with the controls. The occurrence of all malignant and mammary tumours in D-003-treated females was lower than in the controls. The lesions observed were consistent with spontaneous lesions reported in this species. In conclusion, D-003 is not toxic or carcinogenic when given orally to Sprague Dawley rats up to 1500 mg/kg for 2 years, and 1500 mg/kg was a not-observable effect dose.

Rotación de opioides: la metadona como alternativa en el dolor de difícil control. A propósito de un caso / No disponible

Presentamos un caso clínico en el que el uso de metadona redujo de manera importante un dolor no controlado adecuadamente con otros opiáceos. En una revisión amplia de la bibliografía se describe la utilidad de la metadona en rotación de opioides cuando el dolor es refractario a otros opiáceos, si bien no existe un consenso al respecto. El uso de metadona debe reservarse a situaciones de dolor de difícil control. Asimismo es importante considerar el componente neuropático a la hora de decidirnos por el uso de este opiáceo. Aunque existen referencias en cuanto a las dosis equianalgésicas respecto a la morfina, es de suma importancia individualizar la dosis (AU)

We report a case where the use of methadone considerably reduced pain inadequately controlled with other opiates. An extensive literature review described the usefulness of methadone in opioid rotation when refractory pain will not respond to other opiates, but there is no consensus on this topic yet. Methadone must be used in situations where pain is difficult to control. A consideration of the neuropathic component of pain is also relevant when a decision must be made regarding this opioid. While there are references for equianalgesic doses regarding morphine, dose tailoring is extremely important (AU)

In Vitro effect of D-004, a lipid extract of the ground fruits of the Cuban royal palm (Roystonea regia), on rat microsomal lipid peroxidation.

D-004 is a lipid extract of the fruits of the Cuban royal palm (Roystonea regia) containing a mixture of saturated fatty acids. D-004 inhibits prostate hyperplasia (PH) induced with testosterone, in rodents. Since fatty acids inhibit lipid peroxidation (LP), this study investigated whether D-004 prevents in vitro LP. D-004 (0.9-1000 microg/mL) markedly and dose-dependently inhibited in vitro iron-induced LP in native brain and liver microsomes. D-004 showed hydroxyl radical scavenging activity, which could explain partially its antioxidant effect on microsomal iron-induced LP, but it was unable to scavenge superoxide and ABTS radicals, indicating a limited radical scavenging activity. Also, D-004 inhibited CCl4-mediated LP in active liver microsomes through a decreased generation of radical species rather than a radical trapping action on CCl(4)-derived radical species. D-004 also inhibited lipooxygenase (LOX) and cyclooxygenase (COX) activities, and the generation of protein-associated carbonyl groups after LP. Since increased oxidative stress has been linked to PH, the antioxidant effect of D-004 shown here could contribute to explaining its beneficial effects on T-induced PH in rodents. Nevertheless, this study shows only in vitro results. Further studies should investigate whether D-004 also exhibits antioxidant effects in vivo.

Evaluation of the genotoxic potential of Mangifera indica L. extract (Vimang), a new natural product with antioxidant activity.

Mangifera indica L. extract (Vimang) consists of a defined mixture of components (polyphenols, terpenoids, steroids, fatty acids and microelements). It contains a variety of polyphenols, phenolic esters, flavan-3-ols and a xanthone (mangiferin), as main component. This extract has antioxidant action, antitumor and immunemodulatory effects proved in experimental models in both in vitro and in vivo assays. The present study was performed to investigate the genotoxicity potential activity of Vimang assessed through different tests: Ames, Comet and micronucleus assays. Positive and negative controls were included in each experimental series. Histidine requiring mutants of Salmonella typhimurium TA1535, TA1537, TA1538, TA98, TA100 and TA102 strains for point-mutation tests and in vitro micronucleus assay in primary human lymphocytes with and without metabolic activation were performed. In addition, genotoxic effects were evaluated on blood peripheral lymphocytes of NMRI mice of both sexes, which were treated during 2 days with intraperitoneal doses of M. indica L. extract (50-150 mg/kg). The observed results permitted to affirm that Vimang (200-5,000 microg/plate) did not increase the frequency of reverse mutations in the Ames test in presence or not of metabolic activation. Results of Comet assay showed that the extract did not induce single strand breaks or alkali-labile sites on blood peripheral lymphocytes of treated animals compared with controls. On the other hand, the results of the micronucleus studies (in vitro and in vivo) showed Vimang induces cytotoxic activity, determined as cell viability or PCE/NCE ratio, but neither increased the frequency of micronucleated binucleate cells in culture of human lymphocytes nor in mice bone marrow cells under our experimental conditions. The positive control chemicals included in each experiment induced the expected changes. The present results indicate that M. indica L. extract showed evidences of light cytotoxic activity but did not induce a mutagenic or genotoxic effects in the battery of assays used.

Eutanasia y suicidio asistido / Euthanasia and assisted suicide

El propósito del presente artículo es hacer unarevisión de la situación actual en torno al debatepúblico sobre la eutanasia y el suicidio asistido,analizando los argumentos a favor y en contrade modificar la legislación en un sentido permisivo.A continuación se hace una revisión de losdistintos modelos legislativos existentes, con especialatención de los estados que contemplanalgún modelo de exención penal en casos de eutanasia(Holanda, Bélgica, Suiza y Oregon) y seanaliza la legislación española y el impacto delregistro de Instrucciones Previas previsto en laLey de Autonomía del Paciente (Ley 41/2002).Por último se exponen las diferentes formas deeutanasia, los problemas éticos derivados de laaplicación de medidas (como la sedación) queconllevan un “doble efecto” y el papel de las Unidadesde Cuidados Paliativos en un sistema sanitariointegral

The aim of this report is to review the actualsituation around public debate about Euthanasiaand Assisted Suicide, analysing the argumentsagainst and pros for a permissive change in thepenal law. Also, a review over different law modelsis made, with special attention to the statesin which they are any kind of penal exemption(Nederland, Belgium, Switzerland, Oregon). TheSpanish Law is analysed, with evaluation of theimpact made for the new Registry of PreviousInstructions, a tool included in the new Law ofPatient’s Autonomy (Law 41/2002). Finally, differentforms of Euthanasia are exposed, focusingethic problems derived from the application ofextraordinary measures (like sedative’s use)which involve a “double effect” and the role ofthe Palliative Care Units in an overall sanitaryassistance

The innate immune response to Entamoeba histolytica lipopeptidophosphoglycan is mediated by toll-like receptors 2 and 4.

Entamoeba histolytica is a human pathogen that may invade the intestinal mucosa, causing amoebic colitis or hepatic abscesses when the trophozoites travel through the portal circulation to the liver. Lipopeptidophosphoglycan (LPPG) is a molecular pattern of E. histolytica recognized by the human immune system. Here we report that LPPG is exposed on the cell surface of E. histolytica trophozoites, and is recognized by the host through toll-like receptor (TLR) 2 and TLR4. Correspondingly, human embryonic kidney (HEK)-293 cells were rendered LPPG responsive through overexpression of TLR2 or TLR4/MD2. Moreover, co-expression of CD14 enhanced LPPG signal transmission through TLR2 and TLR4. The interaction of LPPG with TLR2 and TLR4 resulted in activation of NF-kappaB and release of interleukin (IL)-10, IL-12p40, tumour necrosis factor (TNF)-alpha, and IL-8 from human monocytes. Consistent with these findings, responsiveness of mouse macrophages lacking TLR2 expression (TLR2-/-) or functional TLR4 (TLR4d/d) to E. histolytica LPPG challenge was impaired while double deficient macrophages were unresponsive. In contrast to wild-type control and TLR2-/- animals succumbing to lethal shock syndrome, TLR4d/d mice were resistant to systemic LPPG challenge-induced pathology.

[Evaluation of the quality of inter-clinic documents. Does their proper filling out by the family doctor affect the reply obtained from the specialist?]. / Evaluación de la calidad del documento de interconsulta. 'Influye la adecuada cumplimentación del médico de familia en la respuesta que obtiene del especialista?

OBJECTIVE: To analyse the filling out of the inter-clinic form (IF) at a centre with special fields of care (CS) and to assess whether its proper filling out in primary care (PC) affects the reply from specialist care. DESIGN: Cross-sectional, descriptive study. SETTING: Primary health care area in the Community of Valencia. PARTICIPANTS: Randomised sample of IFs of patients referred for the first time from PC to specialists. MAIN MEASUREMENTS: Evaluation criteria were grouped in two: those IFs were considered acceptable (IFCA) in which the family doctor included the reason for consultation or his/her diagnostic impression, as well at least one of the following: anamnesis, personal background, physical examination, further tests or current medication. The remaining IFs were considered inadequately filled out (IFCI). RESULTS: The sample analysed for the IF audit of the CS was 392 people. The result of the audit in the specialist clinics was that 243 IFs were blank (62.0%); the specialist doctor was identified in 19% of cases; the diagnosis was given in 23.5%; treatment, in 21%, and the follow-up plan, in 20%. In the PC evaluation, there were no blank IFs; anamnesis was recorded in 41.8%; reason for consultation in 73%; suspected diagnosis in 58.2%, and treatment in 11.5%. The sample to analyse the differences in the filling of the form in specialist care according to the quality of the PC filling out was 529 IFs. 56.3% of the IFs were considered acceptable. No statistically significant differences were found in the filling of any of the criteria of evaluation by the specialist doctor between the IFs from PC of acceptable and inadequate quality, except on the question of specifying treatment. CONCLUSIONS: We found no relationship between the quality of the IF from PC and the reply from specialist care. Currently, the filling out of IFs continues to be deficient.

Oral administration of D-003, a mixture of very long chain fatty acids prevents casein-induced endogenous hypercholesterolemia in rabbits.

D-003 is a mixture of very long chain saturated fatty acids (VLCSFA) purified from sugar cane wax with cholesterol-lowering effects proven in animal models and healthy volunteers. D-003 inhibits cholesterol biosynthesis through the regulation of HMG-CoA reductase activity. Rabbits fed diets enriched with casein develop endogenous hypercholesterolemia (EH), making them a very useful model for determining the mechanism of action of drugs affecting lipids. We examined whether D-003 prevented EH. Rabbits were fed a casein diet for 4 weeks, administered simultaneously with D-003 (5, 50, and 100 mg.kg-1.day-1). As expected, nontreated rabbits became hypercholesterolemic; however, as early as 15 days following administration, the treated group (50 and 100 mg.kg-1.day-1) had significantly decreased total cholesterol and low-density lipoprotein cholesterol (LDL-C). Triglycerides were not affected; however, at study completion, HDL-C levels significantly increased at all the doses assayed. D-003 inhibited de novo synthesis of cholesterol, since the incorporation of 3H2O into sterols in the liver and proximal small bowel was significantly depressed. Also, D-003 significantly raised the rate of removal of [125I]-LDL from serum and significantly elevated [125I]-LDL binding activity to liver homogenates. Taken together, these results show that the efficacy of D-003 in reducing casein-derived hypercholesterolemia could involve, at least partially, an inhibition of hepatic cholesterol biosynthesis, which may elicit a decreased cholesterol concentration in hepatocytes, preventing the loss of hepatic LDL receptors induced by casein administration. However, since casein-induced hypercholesterolemia is also a consequence of a stimulation of cholesterol absorption in the lumen and an increase of the output of cholesterol associated with LDL, the effect of D-003 on cholesterol absorption and LDL synthesis by the liver should be investigated.