Interpenetrating gels in binary suspensions of DNA nanostars.

We experimentally investigate the equilibrium gel formation in a binary mixture of DNA nanostars. The binding rules, encoded in the DNA sequence of the nanostar binding ends, are such that each component is able to form only intra-species bonds. Reducing the excluded volume by properly designing the DNA nanostars, we show that two interpenetrating unconnected gels form in the sample on cooling, each of the two forms at a temperature controlled by the selected binding DNA sequence. The dynamic light scattering correlation functions show a non-common three-step relaxation process due to the splitting of the slow relaxation into two distinct decays, each of them reflecting the relaxation dynamics of one of the two networks.

Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease.

BACKGROUND/AIMS: The aim of this study was to assess the effect of functional ENPP1(ectoenzyme nucleotide pyrophosphate phosphodiesterase 1)/PC-1 (plasma cell antigen-1) and IRS-1 (insulin receptor substrate-1) polymorphisms influencing insulin receptor activity on liver damage in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, whose progression is associated with the severity of insulin resistance. PATIENTS AND METHODS: 702 patients with biopsy-proven NAFLD from Italy and the UK, and 310 healthy controls. The Lys121Gln ENPP1/PC-1 and the Gly972Arg IRS-1 polymorphisms were evaluated by restriction analysis. Fibrosis was evaluated according to Kleiner. Insulin signalling activity was evaluated by measuring phosphoAKT levels by western blotting in a subset of obese non-diabetic patients. RESULTS: The ENPP1 121Gln and IRS-1 972Arg polymorphisms were detected in 28.7% and 18.1% of patients and associated with increased body weight/dyslipidaemia and diabetes risk, respectively. The ENPP1 121Gln allele was significantly associated with increased prevalence of fibrosis stage >1 and >2, which was higher in subjects also positive for the 972Arg IRS-1 polymorphism. At multivariate analysis, the presence of the ENPP1 121Gln and IRS-1 972Arg polymorphisms was independently associated with fibrosis >1 (OR 1.55, 95% CI 1.24 to 1.97; and OR 1.57, 95% CI 1.12 to 2.23, respectively). Both polymorphisms were associated with a marked reduction of approximately 70% of AKT activation status, reflecting insulin resistance and disease severity, in obese patients with NAFLD. CONCLUSIONS: The ENPP1 121Gln and IRS-1 972Arg polymorphisms affecting insulin receptor activity predispose to liver damage and decrease hepatic insulin signalling in patients with NAFLD. Defective insulin signalling may play a causal role in the progression of liver damage in NAFLD.

Metabolic parameters after BioEnterics Intragastric Balloon placement in obese patients.

BACKGROUND: BioEnterics Intragastric Balloon (BIB) is a non-invasive, temporary and relatively safe procedure shown to be effective in the short-term treatment of obesity. Nowadays, BIB does not show convincing evidence of significant long-term weight loss, as compared with conventional management, and data regarding changes in metabolic and nutritional parameters are lacking. METHODS: Forty obese patients [11 males, 29 females, age 36.65+/-10.6 yr, body mass index (BMI) 44.9+/-8.9 kg/m2] were evaluated before and 3 and 6 months after BIB placement by assessment of anthropometric and biochemical parameters as well as nutritional habits. RESULTS: Patients showed a significant reduction in weight (-13.2+/-6.5%), BMI (-13.2%), waist circumference (-6.5 cm), and percentage of fat mass (-19.5%), but not fat-free mass. A significant improvement in insulin sensitivity but not in lipid pattern was seen. After BIB insertion, a significant reduction in caloric intake was paralleled by a redistribution of nutrients; in particular, increased lipid (12.8%) and decreased carbohydrate (-11.7%) percentage, but not absolute intake was observed. CONCLUSION: These data show that BIB improves anthropometric parameters, with reduction of fat mass and preservation of fat-free mass, as well as insulin resistance, but not other metabolic features. The observed change in dietary habits, with a relative increase in lipid intake, once BIB is removed, might favor body weight regain and impact negatively on body weight composition and the other traits of the metabolic syndrome.

Mirtazapine in an HIV-1 infected patient with progressive multifocal leukoencephalopathy.

We describe the clinical course of an HIV-infected patient with progressive multifocal leukoencephalopathy who took mirtazapine for his depression. After six months of therapy the clinical symptoms had not worsened and the neuroradiological image of the brain was unchanged. Further studies are necessary to determine the effect of serotonin receptor antagonist in treating PML associated to HIV.

An unusual complication of gastric banding: recurrent small bowel obstruction caused by the connecting tube.

Laparoscopic adjustable gastric banding (LAGB) is a widely performed surgical procedure for morbid obesity. The application of this mini-invasive approach has given the benefits of shorter hospital stay, less postoperative pain and quicker functional recovery. LAGB complications are related either to the access-port, such as port-site infection or tubing disconnection, or to the band, such as band slippage, pouch dilatation, or intragastric migration. We report a case of recurrent small bowel obstruction caused by the connecting tube around a jejunal loop, in a woman who had under-gone LAGB 3 years before. The diagnosis was difficult to establish because the clinical history and examination were non-specific. A 3-dimensional CT scan was needed to explain the cause of the recurrent abdominal pain, and the small bowel loop was freed from the connecting tube at laparoscopy.

Obese teenagers treated by Lap-Band System: the Italian experience.

BACKGROUND: Little is known about obesity surgery in young and adolescent patients. The aim of this study is to evaluate results of laparoscopic adjustable gastric banding in obese teenagers. METHODS: Patients < or = 19 years old selected from the database of the Italian Collaborative Study Group for Lap-Band were analyzed according to mortality, comorbidities, laparotomic conversion, intra- and postoperative complications, body mass index (BMI), and % excess weight loss (EWL) at different times of follow-up. Data were expressed as mean +/- SD. RESULTS: Fifty-eight (1.5%) of 3813 patients who underwent operation with the Lap-Band System were < or = 19 years old: 47F/11M; mean age, 17.96 +/- 0.99 years (range, 15-19); mean BMI, 46.1 +/- 6.31 Kg/m2 (range, 34.9 - 69.25); mean % excess weight, 86.4 +/- 27.1 (range, 34 - 226.53). Sixteen (27.5%) of the 58 patients were superobese (BMI > or = 50). In 27/58 (46.5%) patients, 1 or more comorbidities were diagnosed. Mortality was absent. Laparotomic conversion was necessary in 1 patient with gastric perforation on the anterior wall. Overall postoperative complications occurred in 6/58 (10.3%). The band was removed in 6/58 (10.3%) patients for gastric erosion (3 patients), psychologic, intolerance (2 patients), and in the remaining patient was converted 2 years after surgery (BMI 31) to gastric bypass or gastric pouch dilatation. Patient follow-up at 1, 3, 5, and 7 years was 48/52 (92.3%), 37/42 (88.1%), 25/33 (75.7%), and 10/10, respectively. At these times, mean BMI was 35.9 +/- 8.4, 37.8 +/- 11.27, 34.9 +/- 12.2, and 29.7 +/- 5.2 Kg/m2. Mean %EWL at the same time was 45.6 +/- 29.6, 39.7 +/- 29.8, 43.7 +/- 38.1, and 55.6 +/- 29.2. Five/25 (20%) patients had < or = 25% EWL at 5 years follow-up, while none of the 10 patients subject to follow-up at 7 years had < or = 25% EWL. CONCLUSIONS: Lap-Band System is an interesting option for teenagers suffering obesity and its related comorbidities, which deserves further investigation.

Unusual presentation of a transparietal cavernous hemangioma of the esophagus.

Hemangiomas are tumors of vascular origin and represent less than 3% of benign neoplasm of the esophagus. We herein report a case of a 55-year-old man, who presented transitory dysphagia and weight loss. A malignancy could not be excluded by a complete work-up, including esophagogram, endoscopic biopsies, CT scan, esophageal endoscopic ultrasonography, PET and thoracoscopic biopsies. Only after partial esophagectomy with laparoscopic gastric mobilization was histological diagnosis obtained. In fact, on microscopic observation of the specimen, the neoplasm appeared to be a cavernous hemangioma of the esophageal submucosa with transparietal extension.

Recreational substance use and tolerance of efavirenz in HIV-1 infected patients.

During the past few years, efavirenz has been increasingly used in the treatment of HIV1 infection. Its main side effect is a syndrome of central nervous system stimulation occurring in 40-50% of adults in the first few weeks of therapy which might be observed at increased frequency in subjects concurrently using recreational substances. We therefore conducted a single center, retrospective study in 134 patients treated with efavirenz and found no significant differences in CNS side effects or discontinuation rates between recreational substance (cocaine, ecstasy, cannabis) users and non-users. Although our study is limited, the results support the idea that efavirenz can be safely prescribed to patients using recreational substances.

Serotonin transporter gene (5-HTTLPR) and major psychoses.

Serotoninergic neurotransmitter systems have been implicated in the pathogenesis of major psychoses. A functional polymorphism (5-HTTLPR) in the upstream regulatory region of the gene (SLC6A4) has been associated with a number of psychiatric disturbances, but conflicting replication followed. The aim of this study was to investigate the possibility that the 5-HTTLPR might be associated with major psychoses. One thousand, eight hundred and twenty inpatients (789 bipolars, 667 major depressives, 66 delusionals, 261 schizophrenics, 37 psychotics not otherwise specified-NOS) and 457 control subjects were included in this study. A subsample of 1235 patients (523 bipolars, 359 major depressives, 259 schizophrenics, 66 delusionals, 28 psychotic NOS) were evaluated for lifetime psychotic symptomatology using the Operational Criteria for Psychotic illness (OPCRIT) checklist. The subjects were also typed for 5-HTTLPR variants using PCR techniques. 5-HTTLPR allele frequencies were not significantly different between controls and bipolars, major depressives, schizophrenics, delusionals and psychotic NOS; genotype analysis also did not show any association. The analysis of symptomatology did not show significant differences. Consideration of possible stratification factors such as sex and age of onset did not significantly influence results. 5-HTTLPR variants are not therefore a liability factor for major psychoses or for major psychoses symptomatology.

No association between dopamine D(2) and D(4) receptor gene variants and antidepressant activity of two selective serotonin reuptake inhibitors.

The possible association of the dopamine receptor D(2) (Ser 311Cys) and D(4) exon 3 (48 base pair repeat) gene variants with the antidepressant activity of selective serotonin reuptake inhibitors (SSRIs) was investigated in a sample of 364 inpatients affected by a major depressive episode treated with fluvoxamine, 300 mg/day (n=266), or paroxetine, 20-40 mg/day (n=98). The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression. Dopamine receptor D(2) (DRD2) and dopamine receptor D(4) (DRD4) allelic variants were determined in each subject by polymerase chain reaction. We observed that DRD2 and DRD4 variants were not associated with response to SSRI treatment. Possible stratification factors, such as sex, diagnosis, presence of psychotic features, depressive symptoms at baseline, paroxetine and fluvoxamine plasma levels, and pindolol augmentation did not significantly influence the observed results. The investigated DRD2 and DRD4 gene variants therefore do not seem to play a major role in the antidepressant activity of SSRIs, at least in the present sample.

Major psychoses symptomatology: factor analysis of 2241 psychotic subjects.

Current nosography classifies major psychoses as separate disorders, but their symptomatological presentation during illness episodes largely overlaps and diagnoses may change during a lifetime. Few analyses of major psychoses symptomatology have been performed so far because of the large number of subjects needed to obtain stable factors. The purpose of this study was, therefore, to identify the symptomatologic structure common to major psychoses based on lifetime symptoms. Two thousand and forty-one inpatients affected by schizophrenic (n=1008), bipolar (n=563), major depressive (n=352), delusional (n=108) and psychotic not otherwise specified disorder (n=210) were rated for lifetime symptoms using the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and included in a factorial analysis. Four factors were obtained, the first consisted of excitement symptoms, the second comprised psychotic features (delusions and hallucinations), the third comprised depression and the fourth disorganization. When scored by the OPCRIT checklist, major psychoses symptomatology is composed of excitement, depressive, delusion and disorganization symptoms.

Influence of 5-HTTLPR and TPH variants on illness time course in mood disorders.

The aim of our study was to investigate gene variants in the long-term outcome of mood disorders. We retrospectively studied a sample of inpatients affected by recurrent and rapid cycling mood disorders. The serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) and the A218C tryptophan hydroxylase (TPH) gene variant were determined using a PCR-based technique. For 5-HTTLPR polymorphism we genotyped 435 inpatients affected by major depressive (n=153), bipolar (n=213) and rapid cycling (n=69) mood disorders and 456 controls; for TPH we genotyped 399 inpatients (MD, n=132; BP, n=203; rapid cycling n=64) and 259 controls. Random Regression Model analysis was used to investigate the longitudinal time course of the illness. 5-HTTLPR and TPH polymorphisms were not associated with mood disorders time course. However we observed an excess of 5-HTTLPR*long alleles among rapid cycling subjects compared to both controls (P=0.018) and remitting mood disorders (P=0.006). TPH frequencies did not differ between mood disorders subtypes. Our results suggest that 5-HTTLPR variants may confer a susceptibility toward rapid cycling mood disorders.

Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression.

BACKGROUND: It has been recently reported that the short variant of the serotonin transporter (5-HTT) gene-linked functional polymorphic region (5-HTTLPR) influences the antidepressant response to certain selective serotonin reuptake inhibitors. The aim of the present study was to test this finding in a sample of major and bipolar depressives, with or without psychotic features. METHODS: One hundred fifty-five inpatients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double-blind design for 6 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique. RESULTS: 5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment, independently from the recorded clinical variables. More specifically, the diagnosis, the presence of psychotic features, and the severity of depressive symptomatology did not influence this association. Conversely, pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects, thus reducing the difference in the response rate among the genotype variants. CONCLUSIONS: If confirmed, these results may improve patient care by helping the clinician to individualize treatment according to the patient's genetic 5-HTTLPR pattern.