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.

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.

Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study.

BACKGROUND: Being the rate-limiting enzyme in the biosynthesis of serotonin, the tryptophan hydroxylase gene (TPH) has been considered a possible candidate gene in bipolar and unipolar affective disorders (BPAD and UPAD). Several studies have investigated the possible role of TPH polymorphisms in affective disorders and suicidal behavior. METHODS: The TPH A218C polymorphism has been investigated in 927 patients (527 BPAD and 400 UPAD) and their matched healthy control subjects collected within the European Collaborative Project on Affective Disorders. RESULTS: No difference of genotype distribution or allele distribution was found in BPAD or UPAD. No statistically significant difference was observed for allele frequency and genotypes counts. In a genotype per genotype analysis in UPAD patients with a personal history of suicide attempt, the frequency of the C-C genotype (homozygosity for the short allele) was lower in UPAD patients (24%) than in control subjects (43%) (chi(2) = 4.67, p =.03). There was no difference in allele or genotype frequency between patients presenting violent suicidal behavior (n = 48) and their matched control subjects. CONCLUSIONS: We failed to detect an association between the A218C polymorphism of the TPH gene and BPAD and UPAD in a large European sample. Homozygosity for the short allele is significantly less frequent in a subgroup of UPAD patients with a history of suicide attempt than in control subjects.

DRD4 exon 3 variants associated with delusional symptomatology in major psychoses: a study on 2,011 affected subjects.

We previously reported an association of DRD4 exon3 long allele variants with delusional symptomatology independently from diagnoses. The aim of this investigation was to study DRD4 in major psychoses and to test the association in a larger sample. We studied 2,011 inpatients affected by bipolar disorder (n = 811), major depressive disorder (n = 635), schizophrenia (n = 419), delusional disorder (n = 104), psychotic disorder not otherwise specified (n = 42), and 601 healthy controls. A subsample of 1,264 patients were evaluated using the OPCRIT checklist and differences of symptomatology factor scores among genetic variants were assessed using one-way analysis of variance (ANOVA). DRD4 allele and genotype frequencies in bipolars, schizophrenics, delusionals, and psychotic NOS were not significantly different from controls; major depressives showed a trend toward an excess of DRD4*Short and DRD4*Short/Short variants versus controls. The ANOVA on factor scores in the whole subsample of 1,264 subjects showed a significant difference on delusion factor in allele analysis (P = 0.007), and in genotype one (P = 0.018), with DRD4*Long containing variants associated with severe symptomatology. The analysis in the replication subjects only (n = 803) showed a trend in the same direction, though not reaching the significance level. This analysis in an enlarged sample suggests that DRD4*Long alleles exert a small but significant influence on the delusional symptomatology in subjects affected by major psychoses.

Serotonin-2C and serotonin-1A receptor genes are not associated with psychotic symptomatology of mood disorders.

The serotonergic system is involved in both pathophysiology and treatment of mood disorders. In the present study we investigated the possible influence of the polymorphisms of the serotonin-1A and 2C receptor genes on the symptomatology of mood disorders. Eighty-four inpatients affected by mood disorders (72 bipolar and 12 major depressive disorder) were assessed by the Operational Criteria Checklist for Psychotic Illness to score their lifetime psychotic symptomatology. The subjects were also typed for 5HT1A and 5HT2C variants using polymerase chain reaction techniques. No association was found between 5HT2C and psychopathology as defined by the four symptomatologic factors used as phenotype definition (mania, depression, delusion, and disorganization) even when bipolar subjects were analyzed separately. Only one subject with the 5HT1A variant was observed. Genetic variation at the 5HT1A and 5HT2C receptor genes does not, therefore, play a major role in the pathogenesis of mood disorders symptomatology. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:161-166, 2000.

Serotonin-2A receptor gene is not associated with symptomatology of schizophrenia.

The serotonin receptor type 2A (5-HT2A) is a primary candidate for involvement in major psychoses. Polymorphisms within the 5-HT2A gene have recently been reported to be associated with a variety of psychopathological conditions. In the present study, we investigated the potential influence of the T102C polymorphism on the psychopathology of schizophrenia. One hundred eighty-eight inpatients affected by schizophrenia (DSM-III-R) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were typed for their 5-HT2A variants by PCR techniques. Mania, depression, delusion and disorganization were the four symptomatologic factors previously derived from our psychotic population that were used to define phenotype in our sample. Genetic variants of the polymorphism under study were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex and age of onset did not reveal any association either. Our results do not, therefore, support the hypothesis that the serotonin receptor 2A gene is a liability factor for the symptomatology of schizophrenia as defined by the OPCRIT checklist. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:84-87, 2000.

Dopamine D3 receptor gene not associated with symptomatology of major psychoses.

Dopamine D3 receptor gene (DRD3) variants have been implicated in the pathogenesis of psychiatric disorders. Many studies, however, have failed to replicate the association of DRD3 with schizophrenia. A possible reason for this may lie in the definition of phenotype, which is traditionally based on psychiatric diagnosis. In this study we investigated the possibility that variants of the DRD3 gene might be associated with symptomatology in a sample of subjects affected by major psychoses. Two hundred and eleven inpatients affected by major psychoses were assessed by the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and were also typed for the DRD3 variants using polymerase chain reaction techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definitions. DRD3 variants were not associated with these symptomatologic factors, and consideration of possible stratification effects, such as sex and psychiatric diagnosis, did not reveal any association either.

No interaction between serotonin transporter gene and dopamine receptor D4 gene in symptomatology of major psychoses.

Previously, we reported an association of the dopamine receptor D4 (DRD4) gene with delusional symptomatology of major psychoses. However, DRD4 variants accounted for only 2% of the phenotypic variance, indicating that contributions from other genes were probable. The serotonin transporter gene is a primary candidate in major psychoses, and a functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has recently been reported to be associated with a number of psychopathological conditions. In the present study we investigated the original cohort of subjects to evaluate the 5-HTTLPR possible influence on the psychopathology of major psychoses in interaction with DRD4. Four hundred and sixty-one inpatients affected by major psychoses were assessed by the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and were also typed for the 5-HTTLPR and DRD4 variants using polymerase chain reaction techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definition. 5-HTTLPR variants did not significantly influence the previously reported association of DRD4 with delusional symptoms. No interaction was observed on the other symptom factors. The serotonin transporter gene does not, therefore, interact with DRD4 in determining the symptomatology of major psychoses.

No interaction of GABA(A) alpha-1 subunit and dopamine receptor D4 exon 3 genes in symptomatology of major psychoses.

Previously, we reported on an association of the dopamine receptor D4 (DRD4) gene with delusional symptomatology of major psychoses. However, despite the strength of the association, it only accounted for 2% of the variance, indicating that contributions from other genes were probable. In the present study, we investigated the original cohort of subjects to evaluate the gene for the gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1). The possible association of GABRA1 with the psychopathology of major psychoses was tested both alone and in interaction with DRD4. Four hundred and sixty-one inpatients affected by major psychoses were assessed by the operational criteria checklist for psychotic illness (OPCRIT) and were also typed for the DRD4 and GABRA1 variants using PCR techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definitions. GABRA1 variants were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex and psychiatric diagnosis also did not reveal any association. GABRA1 variants did not significantly influence the association of DRD4 with delusional symptoms. No interaction was observed on the other symptom factors. The GABA(A) alpha-1 subunit gene does not, therefore, interact with DRD4 in the symptomatology of major psychoses.

Intragastric balloon in obese patients.

BACKGROUND: Since March 1998, 143 BioEnterics Intragastric Balloons (BIB) were placed in 132 obese and morbidly obese patients, to study the clinical possibilities of a new system, both from the point of view of the materials used and the application method. METHODS: 36 patients were male and 96 female; mean age was 43 years (21-70); mean weight was 115.4 kg (67-229), and mean BMI was 41.0 (29-81). 8 patients were affected by severe respiratory insufficiency. We placed and removed the balloon endoscopically under conscious sedation or general anesthesia. BIB was removed in the majority of patients 4 months after insertion. The patients were given a balanced diet of 800-1000 kcal/day; follow-up involved a monthly check-up (routine blood tests, weight control) and a visit every 15 days with the dietitian. RESULTS: Mean weight loss was 14.4 kg; mean reduction in BMI was 5.2. Weight loss was much better in males. The weight loss produced an improvement of the complications associated with the obesity. Complications observed were: balloon intolerance (9 early removals), 1 balloon deflated and passed, 2 cases of gastric ulcer at balloon removal. CONCLUSIONS: The most correct indications for BIB should be: extremely obese patients (BMI>40) in preparation for a bariatric operation; obese patients with BMI 30-35 with a chronic disease otherwise unresolved; patients with BMI<30 in a multidisciplinary approach.