Clinical, environmental, and molecular factors associated to the occurrence and persistence of posttraumatic stress disorder after an earthquake.

Post-traumatic stress disorder (PTSD) is a common and disabling condition with high incidence after an earthquake. The objective of the present study was to identify risk factors associated with the occurrence and persistence of PTSD. Individuals (18-65 years old) who experienced the earthquake of September 19th, 2017, attended the National Institute of Psychiatry (INPRFM) between October and November 2017 (baseline n = 68). Participants were followed 4-6 (first follow-up, n = 40) and 7-9 (second follow-up n = 41) months after the earthquake. Delay returning to normal activities, a negative emotional valence to a previous earthquake, comorbidity with depression, history of childhood maltreatment, and low expression of Glucocorticoid Receptor (GR) were associated with PTSD in the basal assessment. The earthquake-related variable associated with the persistence of PTSD at the second follow-up was that the earthquake had directly affected the participants, either because they were evicted, had damage to their homes, or suffered some injury. Comorbidity with dysthymia, history of childhood maltreatment, and higher severity of PTSD in the basal assessment were associated with persistent PTSD in the second follow-up. The lower expression of the FK506 binding protein 5 (FKBP5) in participants with persistent PTSD in the second follow-up was better explained by childhood physical abuse than with PTSD severity. These findings suggest that acute exposure to earthquake-related stressful situations is relevant for the initial risk of PTSD, while potential long-term stressful conditions are associated with its persistence. Likewise, molecular markers associated with hypothalamus-pituitary-adrenal-axis dysregulation were differentially associated with PTSD diagnosis at the different assessment times.

Development of a diabetes-related nutrition knowledge questionnaire for individuals with type 2 diabetes mellitus in Singapore.

AIM: Diabetes-related nutrition knowledge (DRNK) is essential for the self-care of patients with type 2 diabetes mellitus (T2DM). A specific tool measuring DRNK can help us to understand awareness levels and tailor structured nutrition education programs. Our study aimed to develop a questionnaire to assess DRNK for individuals with T2DM in Singapore. METHODS: An expert panel was formed to consolidate in-depth, culturally suitable, and current information on DRNK. A literature review of diabetes self-care knowledge questionnaires was performed to outline the scope of the questionnaire and generate a question pool. User friendliness was tested in the first draft of the questionnaire (n = 21). Then, a second draft was tested for item difficulty, discrimination index, and internal consistency (n = 62). The final draft was examined for construct validity and test-retest reliability (n = 100). RESULTS: The final questionnaire (four sections: 27 questions) was found to be consistent and reliable. The item difficulty scores of the selected questions ranged from difficult to desirable (2-85). There was fair to good internal consistency (Cronbach's alpha: 0.66, 0.79, 0.56, and 0.78 for Sections 1, 2, 3 and 4, respectively) and construct validity (independent t-test: P < 0.001). Questions in the final questionnaire had an average discrimination index of 0.3 (reasonably good). The questionnaire was revealed to have good test-retest reliability (intraclass correlation: 0.82-0.84). CONCLUSIONS: The DRNK questionnaire is a valid and reliable measure to complement assessment tools measuring self-efficacy/behaviour in individuals with T2DM living in Singapore.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.

Association of Budd-Chiari syndrome and celiac disease.

BACKGROUND AND AIMS: An association between Budd-Chiari syndrome (BCS) and celiac disease (CD) is uncommon. The aims of our study were to investigate the etiology of BCS and to search for a particular HLA Ag pattern among patients. PATIENTS AND METHODS: BCS diagnosis was based on Doppler ultrasound and CD diagnosis on duodenal biopsy, transglutaminase (TGAb) and gliadin antibodies (GAb). Patients were screened for prothrombotic disorders and seven had a PCR-SSO test for HLA genotypes. Patients were treated with anticoagulants and gluten-free diet. RESULTS: Nine patients were included; mean age 27 years (20-42); sex ratio (F/M) 2; mean follow-up duration 31 months (6-54). All patients had endoscopic and histological features of CD. GAb/TGAb were found in 78 % (n=7). Ag HLA found were HLA DQß1(*)02 (n=6) and DQß1(*)03 (n=3). Prothrombotic conditions identified were latent myeloproliferative disorder (n=1), protein C deficiency (n=1), probable factor V Leiden (n=1) and oral contraceptive use (n=1). No prothrombotic state could be identified in the five other patients. CONCLUSION: The BCS-CD association is relatively frequent in our country. Underlying prothrombotic conditions were absent in more than 50 % of cases, suggesting CD plays a role in the occurrence of thrombosis. HLA alleles found are strongly associated with CD, without any particular pattern for the BCS-CD association.

Inflammatory bowel disease and hepatitis B and C.

The risk of viral B and C hepatitis has long been considered to be increased in patients with inflammatory bowel disease (IBD). Blood transfusion and surgery have been identified as the two main risk factors, suggesting nosocomial transmission could be involved. However, recent epidemiologic surveys have found that prevalence in IBD patients is similar to or even lower than that in the general population. Part of the explanation of these recent data may lie in the application of protective measures against viral infection (hepatitis B virus [HBV] vaccination and hepatitis C virus [HCV]-free blood transfusions). Sometimes fatal viral reactivations have been reported in patients on immunosuppressive therapy. Two periods can be distinguished: a) during therapy, a rise in viremia associated with a decrease of immune-mediated hepatic lesions; b) after cessation of therapy, an immune rebound with a destruction of virus-infected hepatocytes. For HBV, preemptive strategy consisting of an antiviral analog is efficient in chronic HBs antigen carriers. For HCV, the impact of immunosuppressive drugs on the natural history is unclear. Most studies report improved comfort although no biopsies were performed before and after immunosuppressive treatment. Physicians managing IBD patients should be aware of the need for screening and institute preventive measures against B and C hepatitis.

[Is it possible to stop nucleos(t)ide analogue based therapy in chronic hepatitis B?]. / Peut-on arrêter un traitement par analogue nucléos(t)idique chez un malade atteint d'hépatite chronique B ?

Nucleos(t)ide analogues are very efficient in the treatment of chronic hepatitis B. In the HBe antigen positive patients, the HBe seroconversion rates range from 12 to 22% after one year of treatment. When HBe seroconversion occure, it is possible to stop the treatment with analogue but only in non cirrhotic patients. If the treatment with analogue is continued for at least 6 months after confirmed HBeAg seroconversion, the HBe seroconversion is durable in 70-90% of patients. The follow up should be done during years. Stopping the treatment is more problematic in HBe antigen negative patients. A virological relapse occur in 44 to 80% of cases and a biochemical relapse occur in 30 to 70% of cases. Stopping the treatment with an analogue in this population should be considered only in a prospective study with careful monitoring and with a long term follow up.

Single-channel function of recombinant type 2 inositol 1,4, 5-trisphosphate receptor.

A full-length rat type 2 inositol 1,4,5-trisphosphate (InsP(3)) receptor cDNA construct was generated and expressed in COS-1 cells. Targeting of the full-length recombinant type 2 receptor protein to the endoplasmic reticulum was confirmed by immunocytochemistry using isoform specific affinity-purified antibodies and InsP(3)R-green fluorescent protein chimeras. The receptor protein was solubilized and incorporated into proteoliposomes for functional characterization. Single-channel recordings from proteoliposomes fused into planar lipid bilayers revealed that the recombinant protein formed InsP(3)- and Ca(2+)-sensitive ion channels. The unitary conductance ( approximately 250 pS; 220/20 mM Cs(+) as charge carrier), gating, InsP(3), and Ca(2+) sensitivities were similar to those previously described for the native type 2 InsP(3)R channel. However, the maximum open probability of the recombinant channel was slightly lower than that of its native counterpart. These data show that our full-length rat type 2 InsP(3)R cDNA construct encodes a protein that forms an ion channel with functional attributes like those of the native type 2 InsP(3)R channel. The possibility of measuring the function of single recombinant type 2 InsP(3)R is a significant step toward the use of molecular tools to define the determinants of isoform-specific InsP(3)R function and regulation.

Transmembrane ion movements elicited by sodium pump inhibition in Helix aspersa neurons.

1. Transmembrane ion movements upon sodium-pump inhibition were studied in identified neurons of the subesophageal ganglia of Helix aspersa. A two-microelectrode, voltage-clamp technique was used to measure transmembrane currents. Changes in intracellular Na+, K+, and Ca2+ concentrations were measured, in unclamped neurons, with Na(+)-sensitive microelectrodes, K(+)-sensitive microelectrodes, and with the fluorescent probe fura-2, respectively. 2. Inhibition of the sodium pump with ouabain (1 mM) elicited an increase in intracellular Na+ concentration, [Na+]i, at an initial rate of 0.42 +/- 0.05 mM/min (mean +/- SE; n = 27), and a membrane depolarization often followed by hyperpolarization. In cells clamped at -50 or -60 mV, ouabain produced an inward shift in membrane-holding current followed by an outward current usually having two components, transient and sustained, respectively. 3. Replacing external Na+ with either N-methyl-D-glucammonium or tetraethylammonium (TEA+) abolished both the ouabain-induced inward membrane current and the rise in [Na+]i, suggesting that Na+ was the charge carrier of the inward current. 4. Cd2+ (400 microM) reduced the rate of rise of the inward current by 60% and the estimated net Na+ flux by 47%. 5. The outward current was abolished by K(+)-channel blockers (10 mM TEA+ and 5 mM 4-aminopyridine or 10 nM apamin). Cd2+ (400 microM), a Ca(2+)-entry blocker, also abolished the outward current. 6. Inhibition of the sodium pump elicited a fall in [K+]i at an initial rate of 1.4 +/- 0.2 mM/min (n = 9 cells). 7. Upon inhibition of the sodium pump in neurons loaded with fura-2, [Ca2+]i increased from an estimated resting level of 147 +/- 37 nM to a maximum of 764 +/- 248 nM (n = 12 cells). 8. The rise in [Ca2+]i in the sustained presence of ouabain was transient, lasting 19.5 +/- 2.8 min, and could be prevented by removal of external Ca2+ before ouabain application or curtailed by removal of external Ca2+ during sustained ouabain exposure. The latter effect was not a consequence of exhaustion of caffeine-sensitive intracellular Ca2+ stores. 9. It is concluded that 1) the rise in [Ca2+]i upon Na(+)-pump inhibition requires the presence of external Ca2+, 2) the outward current observed upon pump inhibition is a Ca(2+)-activated K+ current flowing through apamin-sensitive channels, 3) the resting Na+ permeability involves a Cd(2+)-sensitive component, 4) a large fraction (approximately 30-60%) of the previously described ouabain-induced cell shrinkage may result from Ca(2+)-activated K+ efflux contributing to net solute and water loss.

Effectiveness of magnesium pidolate in the prophylactic treatment of primary dysmenorrhea.

To evaluate Magnesium (Mg) effectiveness in the treatment of primary dysmenorrhea, 30 volunteer dysmenorrheic women of mean age 22.6 years were selected from the out-patients of the Dept. of Obstetrics and Gynaecology of the University of Parma during the period January-December 1989. Patients affected by secondary dysmenorrhea were excluded from the trial. The women considered were asked to self-evaluate their menstrual pain for 6 subsequent cycles using the VAS (Visual Analogue Scale). In the first cycle, as control, no drug was administered; in the following ones, every woman was given 4.5 mg oral Mg Pidolate in 3 administrations daily, from the 7th day preceding the onset of menses till the 3rd day of menstruation. Data were statistically analyzed. In Mg-treated cycles compared with the control one, first day dysmenorrhea progressively decreased, with a significant drop (p < 0.05) from the 1st to the 6th cycle. A similar trend, but not statistically significant, was seen for the 2nd and 3rd day of cycle. No side effect was remarked. These data suggest Mg administration to be a reliable therapy of primary dysmenorrhea.