JQ1 attenuates psychostimulant- but not opioid-induced conditioned place preference.

Epigenetic mechanisms play important roles in the neurobiology of substance use disorder. In particular, bromodomain and extra-terminal domain (BET) proteins, a class of histone acetylation readers, have been found to regulate cocaine conditioned behaviors, but their role in the behavioral response to other drugs of abuse remains unclear. To address this knowledge gap, we examined the effects of the BET inhibitor, JQ1, on nicotine, amphetamine, morphine, and oxycodone conditioned place preference (CPP). Similar to previous cocaine studies, systemic administration of JQ1 caused a dose-dependent reduction in the acquisition of amphetamine and nicotine CPP in male mice. However, in opioid studies, JQ1 did not alter morphine or oxycodone CPP. Investigating the effects of JQ1 on other types of learning and memory, we found that JQ1 did not alter the acquisition of contextual fear conditioning. Together, these results indicate that BET proteins play an important role in the acquisition of psychostimulant-induced CPP but not the acquisition of opioid-induced CPP nor contextual fear conditioning.

Chemical composition and abundance of microplastics in the muscle of commercial shrimp Pleoticus muelleri at an impacted coastal environment (Southwestern Atlantic).

Microplastics (plastics <5 mm) contamination is of worldwide concern and represents a threat to the environment, biota, and humans. Also, they are potential carriers of other contaminants, increasing their adverse effects. In this study, it was analyzed for the first time the chemical composition and abundance of microplastics (MPs) in the commercial shrimp Pleoticus muelleri. Fibers were the predominant plastics (mean: 1.31 fibers g-1 wet weight) in the abdominal muscle of the shrimps being black, the dominant colour. µ-Raman showed that fibers were composed of polyethylene (PE), polypropylene (PP), and cellulose. Also, weathering and topography of the fibers were analyzed through wide-field confocal microscopy. C, O, Si, Al, K, as well as Fe, Zn, S, Ba, Br, and Ti on the plastic surface were detected with SEM/EDS, indicating potential carriers of contaminants. CAPSULE: The shrimp Pleoticusmuelleri ingests fibers with different chemical elements adsorbed on the plastic surface.

Impact assessment of an educational course on vaccinations in a population of medical students.

BACKGROUND: The inadequate knowledge about vaccinations of healthcare workers, including medical doctors, has certainly contributed to the spread of the vaccine hesitancy. Therefore, it is essential to improve the level of knowledge of future doctors. The aim of the study is to evaluate the impact of a course about vaccinations on the knowledge of medical students. METHODS: Medical students were asked to complete an anonymous questionnaire before and after a seminar on vaccination that they willingly attended. The two questionnaires contained the same 10 questions about vaccines. Only the students who had attended the lecture were allowed to fulfil the post-lecture questionnaires through the learning management system (LMS) called "Moodle". A descriptive statistical analysis of the data collected through the comparative evaluation of the answers before and after the seminar was performed. Mann-Whitney test for two independent samples was used to compare medians score before and after the interventions. RESULTS: A total of 100 medical students filled the pre-lecture questionnaire and 81 of them completed the post-lecture questionnaire. Knowledge of the students on the indication of the MMR (Measles-Mumps-Rubella) vaccine strongly improved after the seminar. Moreover, the number of students who would recommend vaccination for pertussis and influenza during pregnancy increased significantly by 37% and 19% respectively after the seminar and those aware of the need for Herpes Zoster vaccination over the age of 65 increased by 22%. DISCUSSION: For future doctors, a thorough knowledge about vaccinations is increasingly required in order to deal with vaccine hesitancy. Extracurricular seminars about vaccines, provided in the second half of the course of study, can have a highly positive impact.

Impact assessment of an education course on vaccinations in a population of pregnant women: a pilot study.

INTRODUCTION: Although the benefits of vaccinations have been extensively demonstrated, vaccination coverage remains unsatisfactory as result of many people's poor knowledge and negative perception of vaccination.We evaluated the impact of an education course on vaccinations in a population of pregnant women. METHODS: A total of 214 pregnant women were invited to participate in this project, which was undertaken at the Obstetrics and Gynaecology Department of Careggi University Hospital in Florence (Italy). Anonymous questionnaires were administered to women before and after the intervention.A descriptive and statistical analysis was carried out in order to compare the responses obtained before and after the intervention. RESULTS: Adherence to the initiative was good (98%): initially, the respondents were not hostile to vaccinations, though many (43%) were poorly or insufficiently informed. The educational intervention had a positive impact. After the intervention, the number of women who rated their level of knowledge of vaccinations as poor or insufficient had decreased by 30% and the number of "hesitant" respondents had decreased with respect to all aspects of the study, especially the decision to be vaccinated during pregnancy. CONCLUSIONS: Hesitancy stems from a lack of accurate information. Healthcare professionals need to improve their communication skills. Appropriate education during pregnancy, when women are more receptive, may have a highly positive impact. These observations need to be considered in the planning of courses to prepare pregnant women for delivery also in other maternal-foetal centres in Italy.

Interaction of vaginal Lactobacillus strains with HeLa cells plasma membrane.

Vaginal lactobacilli offer protection against recurrent urinary and vaginal infections. The precise mechanisms underlying the interaction between lactobacilli and the host epithelium remain poorly understood at the molecular level. Deciphering such events can provide valuable information on the mode of action of commensal and probiotic bacteria in the vaginal environment. We investigated the effects exerted by five Lactobacillus strains of vaginal origin (Lactobacillus crispatus BC1 and BC2, Lactobacillus gasseri BC9 and BC11 and Lactobacillus vaginalis BC15) on the physical properties of the plasma membrane in a cervical cell line (HeLa). The interaction of the vaginal lactobacilli with the cervical cells determined two kinds of effects on plasma membrane: (1) modification of the membrane polar lipid organisation and the physical properties (L. crispatus BC1 and L. gasseri BC9); (2) modification of α5ß1 integrin organisation (L. crispatus BC2, L. gasseri BC11 and L. vaginalis BC15). These two mechanisms can be at the basis of the protective role of lactobacilli against Candida albicans adhesion. Upon stimulation with all Lactobacillus strains, we observed a reduction of the basal oxidative stress in HeLa cells that could be related to modifications in physical properties and organisation of the plasma membrane. These results confirm the strictly strain-specific peculiarities of Lactobacillus and deepen the understanding of the mechanisms underlying the health-promoting role of this genus within the vaginal ecosystem.

Nociceptin receptor activation does not alter acquisition, expression, extinction and reinstatement of conditioned cocaine preference in mice.

Growing evidence indicates that targeting nociceptin receptor (NOP) signaling may have therapeutic efficacy in treating alcohol and opioid addiction. However, little is known about the therapeutic value of selective NOP agonists for the treatment of cocaine dependence. Recently, we identified a highly selective, brain-penetrant NOP small molecule agonist (SR-8993), and using this compound, we previously showed that nociceptin receptor activation attenuated consolidation of fear-related memories. Here, we sought to determine whether SR-8993 also affects the rewarding properties of cocaine. Using a conditioned place preference (CPP) procedure, we show that SR-8993 (3 or 10 mg/kg) failed to disrupt acquisition or expression of cocaine CPP (7.5 or 15 mg/kg) in C57BL/6 mice. Additionally, SR-8993 did not affect rate of extinction or reinstatement (yohimbine- and cocaine-induced) of cocaine CPP. These studies indicate that selective activation of NOP may not be sufficient in reducing behavioral responses to cocaine.

Thujone--cause of absinthism?

Habitual abuse of the wormwood spirit absinthe was described in the 19th and 20th centuries as a cause for the mental disorder "absinthism" including the symptoms hallucinations, sleeplessness and convulsions. A controversial discussion is going on if thujone, a characteristic component of the essential oil of the wormwood plant Artemisia absinthium L., is responsible for absinthism, or if it was merely caused by chronic alcohol intoxication or by other reasons such as food adulterations. To ascertain if thujone may have caused absinthism, absinthes were produced according to historic recipes of the 19th century. Commercial wormwood herbs of two different manufacturers, as well as self-cultivated ones, were used in a concentration of 6 kg/100 l spirit. In addition, an authentic vintage Pernod absinthe from Tarragona (1930), and two absinthes from traditional small distilleries of the Swiss Val-de-Travers were evaluated. A GC-MS procedure was applied for the analysis of alpha- and beta-thujone with cyclodecanone as internal standard. The method was shown to be sensitive with a LOD of 0.08 mg/l. The precision was between 1.6 and 2.3%, linearity was obtained from 0.1 to 40 mg/l (r = 1.000). After the recent annulment of the absinthe prohibition all analysed products showed a thujone concentration below the maximum limit of 35 mg/l, including the absinthes produced according to historic recipes, which did not contain any detectable or only relatively low concentrations of thujone (mean: 1.3 +/- 1.6 mg/l, range: 0-4.3 mg/l). Interestingly, the vintage absinthe also showed a relatively low thujone concentration of 1.8 mg/l. The Val-de-Travers absinthes contained 9.4 and 1.7 mg/l of thujone. In conclusion, thujone concentrations as high as 260 mg/l, reported in the 19th century, cannot be confirmed by our study. With regard to their thujone concentrations, the hallucinogenic potential of vintage absinthes can be assessed being rather low because the historic products also comply with today's maximum limits derived to exclude such effects. It may be deduced that thujone plays none, or only a minor role in the clinical picture of absinthism.

Intraoperative radiation therapy for retroperitoneal soft tissue sarcomas.

Treatment of retroperitoneal soft tissue sarcomas is a difficult clinical problem. Despite the improvement in resection rates in the most recent surgical series, local control still remains the main problem because of the high incidence of local recurrences after surgery. Postoperative radiation therapy has not been always successful because of dose-tolerance of surrounding normal structures, which prevent the delivery of adequate doses of radiation. To overcome this limitations, new therapeutic approaches including external-beam radiation and intraoperative radiation therapy (IORT) have been evaluated at some Institutions. The results of IORT with or without external-beam radiation are reviewed and our experience with preoperative radiation and IORT is reported. As treatment of retroperitoneal sarcomas has evolved into combined modalities including preoperative radiation, maximum surgical resection and IORT, a possible improvement in local control rates has been achieved. However, locoregional failures and the incidence of distant metastases remain a challenge, emphasising the need for further improvement in local and distant treatment. The new phase II trial, activated within the Italian Sarcoma Group, with preoperative concurrent chemo-radiation therapy and IORT is presented.

Nasopharyngeal cancer WHO type II-III: monoinstitutional retrospective analysis with standard and accelerated hyperfractionated radiation therapy.

The aim of this study is to assess the impact of prognostic factors in patients with locoregionally advanced nasopharyngeal cancer (NPC), WHO type II-III, treated with two different radiation therapy (RT) schedules: standard radiation therapy (SRT), and accelerated hyperfractionated radiation therapy (HART), with or without sequential chemotherapy. Between January 1986 and December 1999, 78 consecutive NPC patients were treated either with SRT (until August 1993) or with HART (from September 1993). Of the 78 patients, 60 were males and 18 females, the median age was 56 years (range 14-83). Nine patients had a non-keratinizing carcinoma (WHO type II) and 69 an undifferentiated carcinoma (WHO type III). Five-year overall survival rate (OS) was 62%. Two months after RT, 73 patients were in complete remission. Disease-free survival (DFS) rates at 5 years were: 85% for the HART and 59% for the SRT group, respectively. A multivariate analysis, age (hazard ratio, HR=4.17 for > or = 60 vs. <50 years) and N-stage (HR=3.56 for N3a-N3b vs. N0-N1) were significant for survival, whereas N-stage (HR=8.23 for N3a-N3b vs. N0-N1) and RT schedule (HR=0.30 for HART vs. SRT) were significant for DFS. In our experience, HART achieved higher DFS rates than SRT; however, HART did not favourably affect OS. Toxicity was comparable in the two RT schedules.

Determining the binding capability of the mouse major urinary proteins using 2-naphthol as a fluorescent probe.

The mouse major urinary proteins (MUPs) are an ensemble of isoforms secreted by adult male mice and involved in sexual olfactory communication. MUPs belong to the lipocalin superfamily, whose conserved structure is a beta-barrel made of eight antiparallel beta-strands forming a hydrophobic pocket that accommodates small organic molecules. A detailed knowledge of the molecular mechanism associated to the binding of those molecules can guide protein engineering to devise mutated proteins where the ligand specificity, binding affinity, and release rate can be modulated. Proteins with such peculiar properties may have interesting biotechnological applications for pest control, as well as in food and cosmetic industries. In this work, we demonstrate that the fluorescent molecule 2-naphthol binds to the natural ligand's binding site of MUPs with high affinity. In addition, we show that 2-naphthol binds to MUPs in its protonated form, that its fluorescence is blue-shifted, and the quantum yield is increased, thus confirming the high hydrophobicity of the protein pocket and the absence of proton acceptors inside the binding site. At large the results presented, besides demonstrating that the use of 2-naphthol provides a convenient and quick method for testing MUPs binding activity and to ascertain the quality of the protein preparation, suggest that MUPs can represent an interesting system for studying the photophysical characteristics of fluorescent molecules in a highly hydrophobic environment.

Long-term glycaemic improvement after addition of metformin to insulin in insulin-treated obese type 2 diabetes patients.

AIM: To assess the adjunct effect of metformin to insulin in type 2 diabetes. METHODS: Obese and overweight type 2 diabetes patients treated with insulin for at least 1 year, and with poor glycaemic control (HbA1c > upper reference level + 2%), were included in a randomised, double-blind, placebo-controlled study. Patients were treated for 12 months with either metformin (850 mg b.i.d.) or placebo added to their usual insulin, which was stabilized during a 3-month placebo run-in period, but thereafter attempted to be unchanged. RESULTS: Thirty-seven patients were included. Two patients dropped out during run-in. There were no differences between the metformin (n = 16) and placebo (n = 19) group at baseline. Most patients received multiple insulin injections. Metabolic control was improved by addition of metformin. Mean change in HbA1c from baseline showed highly significant difference between groups at 3, 6, 9 and 12 months. Mean change (percentage units +/- s.d.) at 12 months was -1.1 +/- 0.7% vs. + 0.3 +/- 0.8% (p < 0.001) for HbA1c and -1.4 +/- 2.1 mmol/l vs. + 0.6 +/- 2.2 mmol/l (p = 0.025) for fasting blood glucose. Mean low density lipoprotein (LDL) cholesterol change differed slightly at 6 months, but not at 12 months. There were no changes in insulin dose, blood pressure, body weight, triglycerides, total- and high density lipoprotein (HDL) cholesterol, fibrinogen, C-peptide and laboratory safety variables, including serum B12. Combination therapy was well-tolerated with the same adverse event rate as insulin alone, but more patients with diarrhoea. CONCLUSION: Addition of metformin to insulin induced and maintained clinically significant and consistent long-term reduction of hyperglycaemia in obese, insulin-treated type 2 diabetes patients.

Trypanosoma cruzi: conformational preferences of antigenic peptides bearing the immunodominant epitope of the B13 antigen.

The Trypanosoma cruzi recombinant protein B13 contains tandemly repeated domains and shows high sensitivity in the serological diagnosis of Chagas' disease. It has been shown that the immunodominant epitope of B13 is contained in the GDKPSLFGQAAAGDKPSLF-NH(2) sequence and that the hexapeptide AAAGDK seems to be the "core" of that epitope. Three peptides containing that "core" sequence, one corresponding to the entire repeat motif GDKPSLFGQAAAGDKPSLF-NH(2), pB13, and two smaller fragments, FGQAAAGDK-NH(2), S4, and QAAAGDKPS-NH(2), S5, have been tested in competitive ELISA with recombinant protein B13 in the solid phase against 40 chagasic sera from Brazilian patients. The median percentage inhibition for pB13, S4, and S5 were, respectively, 91, 86, and 68%. The possibility that the distinct antigenic activity of those peptides correlates with the existence of preferential conformational properties has been investigated by CD and NMR spectroscopy. Results indicate their propensity to adopt a helical configuration, centered in the AAAGDK sequence, and whose extent and stability directly correlates with the peptides' antigenicity. The data are discussed in the light of the existence of conformational preferences involving immunodominant epitopes in tandemly repeated antigens.

Radiation treatment of glottic squamous cell carcinoma, stage I and II: analysis of factors affecting prognosis.

PURPOSE: At least in some European Countries, there is still considerable controversy regarding the choice between surgery and radiotherapy for the treatment of patients with early laryngeal-glottic carcinoma. METHODS AND MATERIALS: Two hundred and forty-six patients with laryngeal-glottic neoplasms, Stage I-II, were treated with radical radiotherapy. Before radiotherapy the patients were evaluated to determine the surgical procedure of choice. Either 66-68.4 Gy (33-38 fractions) or 63-65 Gy (28-29 fractions) of radiation therapy (RT) were administered. The overall disease free survival was determined for each subgroup of patients. Univariate and multivariate analyses were performed to determine significant prognostic variables. RESULTS: Five- and 10-year overall survival rates were 83 and 72%, respectively. At a median follow-up of 6 years 204 patients are alive and disease free. No patient developed distant metastases. One patient died of a large local recurrence, 38 patients died of causes unrelated to their tumor, and 3 patients were lost to follow-up. The multivariate analysis confirmed that performance status (PS), macroscopic presentation of the lesion, and persistence of dysphonia after radiotherapy are significant prognostic factors. CONCLUSIONS: According to the multivariate analysis, the patients with PS > 80 and with exophytic lesions are eligible for radical RT. The surgical procedure proposed for each patient was not found to be an independent prognostic factor.

Glucose tolerance and mortality, including a substudy of tolbutamide treatment.

Mortality according to glucose tolerance was studied to determine the prognosis of impaired glucose tolerance. Among 2500 persons tested in a community screening programme in 1962-1965 and followed-up for mortality to the end of 1987, age-sex-adjusted mortality rates were 37.9 +/- 1.9, 53.6 +/- 4.2, and 70.1 +/- 3.6 deaths per 1000 person-years (+/-SE) in those with normal glucose tolerance, impaired glucose tolerance, and diabetes by World Health Organization criteria at baseline. Age-sex-adjusted mortality rates due to ischaemic heart disease were 14.3 +/- 1.1, 16.3 +/- 2.4, and 25.8 +/- 2.0 deaths per 1000 person-years, respectively. Using criteria predating those of the World Health Organization 147 men with abnormal glucose tolerance were entered into a randomized clinical trial in which 49 were treated with tolbutamide for approximately 10 years. Those treated had lower mortality rates from all causes (mortality rate ratio = 0.66, 95% confidence interval = 0.39, 1.10) and from ischaemic heart disease (mortality rate ratio = 0.42, 95% confidence interval = 0.16, 1.12) than those not receiving tolbutamide. Thus mortality rates are increased in persons with impaired glucose tolerance and diabetes, and the small clinical trial suggests that tolbutamide may be beneficial in men with abnormal glucose tolerance.

Chiral recognition by the copper(II) complex of 6-deoxy-6-N-(2-methylaminopyridine)-beta-cyclodextrin.

A modified beta-cyclodextrin bearing a 2-aminomethylpyridine binding site for copper(II) (6-deoxy-6-[N-(2-methylamino)pyridine)]-beta-cyclodextrin, CDampy) was synthesized by C6-monofunctionalization. The acid-base properties of the new ligand in aqueous solution were investigated by potentiometry and calorimetry, and its conformations as a function of pH were studied by NMR and circular dichroism (c.d.). The formation of binary copper(II) complexes was studied by potentiometry, EPR, and c.d.. The copper(II) complex was used as chiral selector for the HPLC enantiomeric separation of underivatized aromatic amino acids. Enantioselectivity in the overall stability constants of the ternary complexes with D- or L-Trp was detected by potentiometry, whereas the complexes of the Ala enantiomers did not show and difference in stability. These results were consistent with a preferred cis coordination of the amino group of the ligand and of the amino acid in the ternary complexes ("cis effect"), which leads to the inclusion of the aromatic side chain of D-Trp, but not of that of L-Trp. In Trp-containing ternary complexes, the two enantiomers showed differences in the fluorescence lifetime distribution, consistent with only one conformer of D-Trp and two conformers of L-Trp, and the latter were found to be more accessible to fluorescence quenching by acrylamide and KI.

Characterizing the secondary hydration shell on hydrated myoglobin, hemoglobin, and lysozyme powders by its vitrification behavior on cooling and its calorimetric glass-->liquid transition and crystallization behavior on reheating.

For hydrated metmyoglobin, methemoglobin, and lysozyme powders, the freezable water fraction of between approximately 0.3-0.4 g water/g protein up to approximately 0.7-0.8 g water/g protein has been fully vitrified by cooling at rates up to approximately 1500 K min-1 and the influence of cooling rate characterized by x-ray diffractograms. This vitreous but freezable water fraction started to crystallize at approximately 210 K to cubic ice and at approximately 240 K to hexagonal ice. Measurements by differential scanning calorimetry have shown that this vitreous but freezable water fraction undergoes, on reheating at a rate of 30 K min-1, a glass-->liquid transition with an onset temperature of between approximately 164 and approximately 174 K, with a width of between approximately 9 and approximately 16 degrees and an increase in heat capacity of between approximately 20 and approximately 40 J K-1 (mol of freezable water)-1 but that the glass transition disappears upon crystallization of the freezable water. These calorimetric features are similar to those of water imbibed in the pores of a synthetic hydrogel but very different from those of glassy bulk water. The difference to glassy bulk water's properties is attributed to hydrophilic interaction and H-bonding of the macromolecules' segments with the freezable water fraction, which thereby becomes dynamically modified. Abrupt increase in minimal or critical cooling rate necessary for complete vitrification is observed at approximately 0.7-0.8 g water/g protein, which is attributed to an abrupt increase of water's mobility, and it is remarkably close to the threshold value of water's mobility on a hydrated protein reported by Kimmich et al. (1990, Biophys. J. 58:1183). The hydration level of approximately 0.7-0.8 g water/g protein is approximately that necessary for completing the secondary hydration shell.

Pattern of cytokines and pharmacomodulation in sepsis induced by cecal ligation and puncture compared with that induced by endotoxin.

The production of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 and their pharmacomodulation were evaluated in a model of polymicrobial sepsis induced in mice by cecal ligation and puncture (CLP) and were compared with the effects of endotoxin (lipopolysaccharide [LPS]) treatment. LPS levels rose as early as 1 h after CLP and increased further after 2 and 21 h. TNF-alpha was detectable in serum, spleen, liver, and lungs during the first 4 h, with a peak 2 h after CLP. IL-1 beta was measurable in serum after 24 h, and levels increased significantly in spleen and liver 4 and 8 h after CLP. IL-6 levels increased significantly in serum throughout the first 16 h after CLP. These cytokines were detectable after LPS injection, with kinetics similar to those after CLP but at a significantly higher level. To cast more light on the differences between these two animal models of septic shock, we studied the effects of different reference drugs. Pretreatment with dexamethasone (DEX); ibuprofen (IBU), an inhibitor of cyclooxygenase; and NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, significantly reduced survival, while chlorpromazine (CPZ) and TNF did not affect it. Only the antibiotics and pentoxifylline significantly increased survival in mice with CLP. However, CPZ and DEX protected the mice from LPS mortality. On inhibiting TNF-alpha with DEX, CPZ, or pentoxifylline, survival was reduced, unchanged, and increased, respectively, and on increasing TNF-alpha with IBU and TNF, survival was decreased or unchanged, respectively, suggesting that the modulation of this cytokine does not play a significant role in sepsis induced by CLP, unlike treatment with LPS. The negative effects of IBU and N(G)-nitro-L-arginine suggest a protective role by prostaglandins and nitric oxide in sepsis induced by CLP.

Short-term mortality in childhood onset insulin-dependent diabetes mellitus: a high frequency of unexpected deaths in bed.

Mortality and the causes of death have been studied in a population-based cohort of 4919 childhood onset IDDM cases. Enrolment began in 1977 and at the time of study there had been a maximum duration of disease of 13.5 years, with a total of 33,721 person years at risk. Survival status was ascertained by linkage to the Swedish Cause-of-Death register. Death certificates, autopsy protocols, and hospital records were scrutinized for classification of causes of deaths. Twenty males and 13 females with IDDM died before the age of 28.5 years. This corresponds to a Standardized Mortality Rate for age of 262% (95% confidence limits, 172-400) for the boys and 384% (95% confidence limits, 232-635) for girls. Seven patients died of ketoacidosis, four at onset of diabetes. Nine cases were found 'dead in bed', having been seen apparently healthy 1-2 days before death. One of these cases had signs of cerebral haemorrhages at autopsy and another one had signs of bite marks in the mouth, but otherwise all autopsies were normal and no evidence of alcohol or other intoxication was found. In a well-educated population with good access to inexpensive diabetes care, there is still a two- to threefold excess mortality among young onset insulin-dependent diabetic individuals including a high frequency of unexplained deaths in bed.

Simvastatin treatment of hypercholesterolemia in patients with insulin dependent diabetes mellitus.

The effects of 16 weeks therapy with the HMG-CoA reductase inhibitor Simvastatin 10-20 mg (n = 12) was compared to placebo (n = 13) in 25 euthyreoid males with insulin dependent diabetes mellitus and fasting total serum cholesterol above 6 mmol/l. Insulin dependence was defined as a glucagon stimulated C-peptide level less than 0.6 mmol/l. The study was placebo-controlled, double-blind with a parallel group design. Body weight, blood pressure, glycemic control as well as liver enzymes were unchanged and simvastatin was well tolerated by all patients. Ophthalmological slitlamp examination before and at the end of the study period did not show development of new lenticular opacities. Simvastatin decreased serum total cholesterol from 6.7 +/- 1.0 mmol/l (mean +/- SD) to 4.9 +/- 0.4 (p < 0.001 vs. placebo) and LDL-cholesterol from 4.6 +/- 0.7 mmol/l to 2.8 +/- 0.3 (p < 0.001 vs. placebo). HDL-cholesterol and triglycerides remained unaltered. A positive influence on the atherosclerotic process in patients with insulin dependent diabetes mellitus remains, however, to be proven.