Biomedical subjects

L Franchini

Publications and source records attributed to L Franchini.

At least 19 recordsLinked to original sources

PubMed2005

Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development.

To gain insights into the role of purinergic receptors in oligodendrocyte development, we characterized the expression and functional activity of P2 receptors in cultured rat oligodendrocyte progenitors and investigated the effects of ATP and its breakdown products on the migration and proliferation of this immature glial cell population. Using Western blot analysis, we show that oligodendrocyte progenitors express several P2X (P2X(1,2,3,4,7)) and P2Y (P2Y(1,2,4)) receptors. Intracellular Ca(2+) recording by Fura-2 video imaging allowed to determine the rank potency order of the P2 agonists tested: ADPbetaS = ADP = Benzoyl ATP > ATP > ATPgammaS > UTP, alpha,beta-meATP ineffective. Based on the above findings, on pharmacological inhibition by the antagonists oxATP and MRS2179, and on the absence of alpha,betameATP-induced inward current in whole-cell recording, P2X(7) and P2Y(1) were identified as the main ionotropic and metabotropic P2 receptors active in OPs. As a functional correlate of these findings, we show that ATP and, among metabotropic agonists, ADP and the P2Y(1)-specific agonist ADPbetaS, but not UTP, induce oligodendrocyte progenitor migration. Moreover, ATP and ADP inhibited the proliferation of oligodendrocyte progenitors induced by platelet-derived growth factor, both in purified cultures and in cerebellar tissue slices. The effects of ATP and ADP on cell migration and proliferation were prevented by the P2Y(1) antagonist MRS2179. By confocal laser scanning microscopy, P2Y(1) receptors were localized in NG2-labeled oligodendrocyte progenitors in the developing rat brain. These data indicate that ATP and ADP may regulate oligodendrocyte progenitor functions by a mechanism that involves mainly activation of P2Y(1) receptors.

Adenosine Diphosphate↗

PubMed2003

N-terminal truncation of the variable subunit stabilizes spinach ferredoxin:thioredoxin reductase.

The variable subunit of spinach ferredoxin:thioredoxin reductase (FTR) has an extended N-terminus compared to FTRs from other sources and this was proposed to contribute to the instability of the protein. We constructed two N-terminal truncation mutants of recombinant FTR by removing 16 or 24 residues from the variable subunit. The mutant proteins are readily expressed and show half-saturation values (S(0.5)) for ferredoxin and thioredoxin f comparable to WT. However, truncation increases significantly their stability. Using the stabilized FTR an exposed Cys on its thioredoxin contact surface could be substituted without altering its properties, whereas the replacement of an active site Cys by Ser completely destabilized the protein.

Amino Acid Sequence↗

PubMed2001

Long-term treatment with citalopram in patients with highly recurrent forms of unipolar depression.

The authors evaluated the efficacy and safety of citalopram in a 28-month study in 48 inpatients with highly recurrent forms of unipolar depression. The patients, who each had at least one depressive episode during the 18 months preceding the index episode, were openly treated with citalopram, 40 mg/day. Thirty-six of the patients had a stable response to citalopram and continued treatment as outpatients for 4 months. No relapses were observed. At the time of recovery, 32/36 subjects received maintenance treatment with citalopram (40 mg) for an additional 24 months. At the end of the study, 11/32 patients experienced a single new recurrence.

Adult↗

PubMed2001

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.

Adult↗

PubMed2001

A neural network approach to the outcome definition on first treatment with sertraline in a psychiatric population.

Therapy decision is one of the most important tasks clinicians have to perform in their clinical practice. The decision process requires taking into account many different factors. The Authors have proposed a neural computing approach for supporting clinical decision analysis. The mathematical model of artificial neural network (ANN) has been applied on a pool of clinical information gathered through case description freely filled by senior psychiatrists into 416 clinical charts. Sertraline, as drug for treatment, has been chosen since its clinical uses range from treatment of depression to that of many other psychiatric clinical conditions so that it has been thought to be a good candidate to this type of study. The ANN performance in forecasting successful and unsuccessful treatment cases showed an overall accuracy of classification of 97.35%. This result suggests a possible future application of this method to obtain a reliable prediction of a given psychiatric patient outcome during a specific psychopharmacological therapy, optimising the decisional making process.

Adolescent↗

PubMed2000

Will a second prophylactic treatment with a higher dosage of the same antidepressant either prevent or delay new depressive episodes?

Fifty-seven highly recurrent unipolar patients, excluded from previous long-term studies with selective serotonin reuptake inhibitors (SSRIs) after they experienced a new recurrence, were acutely treated with the full dosage of the SSRIs they were on. Fifty-one of them (89.5%) had a sustained response and entered into the 4-month continuation therapy. During this phase, no relapse was observed. At the end of it, all patients gave their written informed consent to be enrolled in a 24-month long-term therapy, maintaining the same treatment dosage of fluvoxamine 300 mg/day, sertraline 150 mg/day, or paroxetine 40 mg/day. At the end of the study, 28 out of the 51 outpatients (54.9%) showed a further recurrence. Nevertheless, second recurrences observed during this second maintenance therapy were less severe than first recurrences, decreasing from 25.1+/-3.4 to 21.6+/-3.3 (P<0.0001), respectively. Considering the clinical characteristics of patients, we found that a high number of prior depressive episodes and an early age at onset of illness may predict a bad outcome. Moreover, patients with a longer duration of euthymia during a first maintenance period are less likely to have a new episode of depression.

Adult↗

PubMed2000

A dicistronic construct for the expression of functional spinach chloroplast ferredoxin:thioredoxin reductase in Escherichia coli.

Ferredoxin:thioredoxin reductase (FTR) is a heterodimeric Fe&z.sbnd;S containing disulfide reductase involved in the light-dependent activation of photosynthetic enzymes. We have designed a dicistronic construct for the heterologous expression of this nucleus encoded chloroplast protein in Escherichia coli. The coding sequences for the two mature subunits have been inserted in tandem into the expression vector pET-3d. This dicistronic construct is correctly translated yielding soluble, perfectly functional FTR. The recombinant enzyme is composed of both subunits, contains the correctly inserted Fe&z.sbnd;S cluster as evidenced by its spectral properties and is indistinguishable from the enzyme isolated from leaves in its capacity to activate chloroplast fructose-1,6-bisphosphatase, one of the well known light activated enzymes of the Calvin cycle.

Journal Article↗

PubMed2000

Patterns of symptom improvement during antidepressant treatment of delusional depression.

We assessed the pattern of changes in depressive symptoms in delusional depressed inpatients treated openly with 300 mg/day of fluvoxamine for 6 weeks. We studied 59 inpatients affected by bipolar (n=23) and major depressive (n=36) disorders with psychotic features (DSM-IV) who showed complete responses to fluvoxamine treatment. Responses were evaluated using the Hamilton Rating Scale for Depression (HAMD-21, divided into: Core, Activity, Psychic anxiety, Somatic anxiety and Delusion clusters) administered at baseline and weekly until the 6th week. Random Regression Model (RRM) analysis was used to investigate the longitudinal time course of HAMD clusters. HAMD depressive symptom clusters decreased in a parallel manner from baseline to the end of the 6-week trial. The RRM analysis revealed no significant difference between HAMD clusters and the time course of the total HAMD score during treatment. Our data indicate that there is a simultaneous decrease in depressive symptoms during antidepressant treatment of delusional depressives.

Adult↗

PubMed2000

Melancholic features and response to lithium prophylaxis in mood disorders.

Clinical predictors of the efficacy of lithium prophylaxis in mood disorders have great potential value. Melancholic features during depressive phases have been both proposed and rejected as valid predictors of favorable outcome. The aim of the present study is to describe the validity of melancholic features during depressive phases as predictors of the prophylactic efficacy of lithium. Sixty-one subjects affected by bipolar (n = 51) and major depressive (n = 10) disorder were followed prospectively for an average of 53 months. All subjects were evaluated as a lifetime perspective at intake, by the Operational Criteria checklist for psychotic illness (OPCRIT). Melancholic features were correlated with outcome only when controlling for time of first lithium administration. These two variables accounted for more than 30% of the total variance in lithium response. Others clinical factors such as polarity, delusions, gender, onset, personality disorders, and family history of mood disorders did not influence the observed association. Our preliminary findings suggest that melancholic features may be associated with favorable lithium prophylactic outcome in mood disorders.

Adult↗

PubMed2000

Four-year follow-up study of sertraline and fluvoxamine in long-term treatment of unipolar subjects with high recurrence rate.

We prolonged from 24 to 48 months a follow-up study of unipolar subjects with high recurrence rate treated with fluvoxamine (N=25) and sertraline (N=22). During the two-year additional period a significant risk of recurrences was observed during the third year of follow-up, without differences in the two long-term therapy groups. During the fourth year no patients showed new episodes of illness.

Adult↗

PubMed2000

Venlafaxine versus fluvoxamine in the treatment of delusional depression: a pilot double-blind controlled study.

BACKGROUND: Previous studies have reported the efficacy of selective serotonin reuptake inhibitors as monotherapy in the treatment of delusional depression. The clinical efficacy of venlafaxine, a serotonin-norepinephrine reuptake blocker, has been demonstrated in the treatment of patients with moderate-to-severe depression, but, to date, no evidence is available about its use in depressed patients with psychotic features. METHOD: Under double-blind conditions, 28 hospitalized patients who met DSM-IV criteria for major depression, severe with psychotic features, were randomly assigned to receive fluvoxamine or venlafaxine, 300 mg/day, for 6 weeks. Severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D) and the Dimensions of Delusional Experience Rating Scale (DDERS) administered at baseline and every week thereafter. Side effects were also recorded. Clinical response was defined as a reduction of the scores in the 21-item HAM-D to 8 or below and in the DDERS to 0. RESULTS: At study completion, the response rates were 78.6% (N = 11) and 58.3% (N = 7) for fluvoxamine and venlafaxine, respectively. No significant difference was found between drugs (Fisher exact test, p = .40). Analysis of covariance on HAM-D scores did not reveal a significantly different decrease of depressive symptomatology between the 2 treatment groups (p = .14). Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded. The overall safety profile of both fluvoxamine and venlafaxine was favorable. CONCLUSION: The results of this pilot double-blind trial show that fluvoxamine is useful in the treatment of delusional depression and suggest that venlafaxine may also be an effective compound in the treatment of this disorder. The latter finding, although promising, warrants further replication in a larger sample of patients.

Adult↗

PubMed1999

Dopamine receptor D2 and D4 genes, GABA(A) alpha-1 subunit genes and response to lithium prophylaxis in mood disorders.

Lithium is an effective prophylactic agent in mood disorders, and genetic factors are likely to modulate individual susceptibility to lithium treatment. The aim of this study is to investigate the influence of dopamine receptor D2 (DRD2), D4 exon 3 (DRD4), and gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1) gene variants on the efficacy of lithium prophylaxis in mood disorders. Patients with mood disorders (N = 125: bipolar subtype, n = 100; major depressive disorder subtype, n = 25) were followed prospectively for an average of 53 months and were typed for DRD2 (Ser311/Cys311: n = 121, VNTR: n = 63), DRD4 (n = 125) and GABRA1 (n = 61) variants using polymerase chain reaction (PCR) techniques. DRD2, DRD4 and GABRA1 variants were not associated with response to lithium. A trend was observed toward a better outcome of DRD4* 2/4 subjects, but it was due to only two subjects. Consideration of possible stratification effects like gender, polarity, family history, age at onset and duration of lithium treatment did not reveal any association either. DRD2, DRD4 and GABRA1 variants therefore do not appear to be associated with the outcome of lithium prophylaxis in mood disorders.

Adult↗

PubMed1999

Early onset of lithium prophylaxis as a predictor of good long-term outcome.

The recurrence rates during lithium preventive treatment were investigated in a sample of 270 Mood Disorder subjects subdivided according to their onset time for lithium prophylaxis as very early (within 5 years from the onset of illness), early (6-10 years), late (11-20 years) and very late (more than 21 years). 131 subjects of the sample followed for 4 years prolonged the observation for a further period of 8 years. Results indicated that beginning lithium therapy within the first ten years of illness predicts better preventive outcomes than beginning prophylaxis later, both in major depression, recurrent and bipolar patients.

Adult↗

PubMed1999

Social adjustment and self-esteem in remitted patients with mood disorders.

Mood disorders are characterized by manic and depressive episodes alternating with normal mood. While social function is heavily impaired during episodes of illness, there are conflicting opinions about inter-episode function. The present paper focuses on self-esteem and social adjustment in remitted mood disorders patients. Patients with mood disorders (99 bipolar and 86 major depressive subjects, in remission) were compared with a group of 100 control subjects. The self-esteem scale (SES) and the social adjustment scale (SAS) were used to measure self-esteem and social adjustment, respectively, in both groups of subjects. Patients with mood disorder exhibited worse social adjustment and lower self-esteem than control subjects. These results strongly confirm previous observations of poor inter-episode function in patients with mooddisorder.

Adult↗

PubMed1999

Two-year maintenance treatment with citalopram, 20 mg, in unipolar subjects with high recurrence rate.

BACKGROUND: The efficacy of citalopram, 20 to 60 mg/day, in relapse prevention in major depression was demonstrated in 6-month placebo-controlled studies. The authors tested the efficacy of citalopram, 40 mg/day, in relapse prevention over a 4-month period and citalopram, 20 mg/day, in recurrence prevention over a 24-month period. METHOD: Fifty inpatients with recurrent major depressive disorder (DSM-IV criteria) who had had at least one depressive episode during the 18 months preceding the index episode were openly treated with citalopram, 40 mg/day. Thirty-six subjects had a stable response to citalopram and remained in the continuation treatment with citalopram, 40 mg/day, for 4 months as outpatients. At the time of recovery, 32 patients gave their written informed consent before entering the 24-month maintenance period with citalopram, 20 mg/day. They were evaluated monthly by trained psychiatrists on the basis of the 21-item Hamilton Rating Scale for Depression. Every 3 months, patients were given the Sheehan Disability Scale, a self-rating instrument, to assess their psychosocial adjustment. RESULTS: No relapse was observed in the 4-month continuation period. Sixteen (50%) of 32 patients who entered the 24-month maintenance period had a new recurrence. Patients with recurrence showed a persistent moderate disability on Sheehan Disability Scale score, while no further differences were highlighted in clinical and demographic characteristics between patients with and without recurrence. CONCLUSION: In agreement with previous findings, these data suggest that a full dose of antidepressant is strongly recommended in prophylactic therapy of patients with recurrent major depression. Moreover, it appears that psychosocial impairment may increase the risk of recurrence, thus conditioning a poor outcome.

Adult↗

PubMed1998

Faster onset of action of fluvoxamine in combination with pindolol in the treatment of delusional depression: a controlled study.

This double-blind, controlled study was undertaken to investigate whether the addition of pindolol could improve the therapeutic response to fluvoxamine of depressed patients with psychotic features. After a 1-week placebo run-in period, 72 patients received fluvoxamine 300 mg/day in combination with placebo or pindolol 7.5 mg/day. At study completion, 28 (80%) of 35 patients treated with fluvoxamine plus placebo and 29 (80.5%) of 36 patients treated with fluvoxamine plus pindolol were categorized as responders (reduction of their score on the 21-item Hamilton Rating Scale for Depression to 8 or less and on the Dimension for the Delusional Experience Rating Scale to 0). In the third and fourth weeks, the response rates were significantly superior in the fluvoxamine plus pindolol group (p = 0.0001, p = 0.023, respectively). Treatment response seemed to be unrelated to the demographic and the clinical characteristics recorded. No significant difference was found comparing plasma levels of fluvoxamine between groups, thus excluding a pharmacokinetic interaction. Other than mild nausea and sedation in a few patients, treatments were well tolerated. No medically significant adverse events occurred. Depressed patients with psychotic features who were administered pindolol experienced a more rapid improvement during fluvoxamine treatment. Thus, the combination of fluvoxamine with pindolol may be a useful pharmacologic strategy in the treatment of this disorder. A rapid clinical response in such patients is of relevance in clinical practice as well as in economic fields, given the direct and indirect costs of depression.

Adolescent↗

PubMed1998

Mode of inheritance in mood disorder families according to fluvoxamine response.

Mood disorders are known to cluster within families, but the mode of transmission remains largely unknown. The purpose of our analysis was to determine whether selection of a sample that was homogeneous in its response to an antidepressant provided stronger evidence for a single major locus. Complex segregation analysis was applied to a sample of 171 Italian families of bipolar and unipolar probands that were responsive to the antidepressant fluvoxamine. We used regressive logistic analyses to determine the best fit from among environmental, arbitrary Mendelian, dominant, recessive and additive models. For the 171 affective families with probands that were responsive to the antidepressant fluvoxamine, a Mendelian model of inheritance was rejected. When considering 68 families of bipolar probands, the best fit was obtained for a Mendelian dominant model of transmission. The identification of a Mendelian mode of transmission in bipolar subjects who were selected according to their response to fluvoxamine supports the use of a pharmacological criterion as a tool for identifying true genetic disorders.

Adult↗

PubMed1998

Dose-response efficacy of paroxetine in preventing depressive recurrences: a randomized, double-blind study.

BACKGROUND: The authors evaluated and compared the efficacy of 20 mg versus 40 mg of paroxetine in a randomized, double-blind, parallel-group study during a maintenance period of 28 months. METHOD: Ninety-nine inpatients with recurrent, unipolar depression (DSM-IV criteria) who had at least 1 depressive episode during the 18 months preceding the index episode were openly treated with paroxetine 40 mg/day. Seventy-two subjects had a stable response (Hamilton Rating Scale for Depression score < 8) to paroxetine treatment and remained in the continuation treatment as outpatients for 4 months. At the time of recovery, 68 patients were randomly assigned to 1 of the 2 maintenance treatment groups: paroxetine 20 mg or paroxetine 40 mg daily. RESULTS: Sixty-seven patients completed the 28-month follow-up period. Seventeen (51.5%) of 33 patients in the 20-mg paroxetine regimen had a single recurrence compared with 8 (23.5%) of 34 subjects in the 40-mg dose regimen (chi2 = 5.56, p = .018). CONCLUSION: These data suggest that a full dose of paroxetine is recommended in unipolar patients who are at high risk for recurrent depressive episodes.

Adult↗