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1.
Dig Liver Dis ; 52(7): 695-699, 2020 07.
Article in English | MEDLINE | ID: mdl-32425732

ABSTRACT

We conducted a survey to investigate to what extent the fear of COVID-19 has influenced the patients decision to undergo or to cancel endoscopic procedures. We collected data from 847 patients from 13 centres. The main indication for endoscopy was anemia, followed by pain and unexplained weight loss. The percentage of not presenters progressively increased throughout the three weeks of study, from 15.1% at the beginning to 48.2% at the end. 37 (34.2%) upper GI endoscopies and 112 (56.3 %) colonoscopies showed an organic cause explaining the symptoms presented by the patients, respectively; 5 cases of gastric cancer (4.6%) and 16 cases of colorectal cancer (CRC) (6.0%), respectively, were detected; during the second week the percentage of organic diseases found at upper endoscopy was 19 (33.3%) with 5 cancer (8.7%), and 61 (49.1% ) at colonoscopy, with 2 CRC (1.6%); finally, during the third week the corresponding figures were 19 (48.7%) for upper GI examinations, with 3 gastric cancers (7.7%), and 43 (60.5%) with 4 (6.5%) CRC cases found.We conclude that patients weighted the fear of having a clinically relevant disease with the fear of becoming infected by coronavirus, and a relevant percentage of them (29.4%) decided not to attend the endoscopy suites at the scheduled date.


Subject(s)
Colorectal Neoplasms , Coronavirus Infections , Endoscopy, Gastrointestinal , Fear , No-Show Patients , Pandemics , Pneumonia, Viral , Stomach Neoplasms , Attitude to Health , Betacoronavirus/isolation & purification , COVID-19 , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/physiopathology , Colorectal Neoplasms/psychology , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Coronavirus Infections/transmission , Disease Outbreaks , Endoscopy, Gastrointestinal/psychology , Endoscopy, Gastrointestinal/statistics & numerical data , Female , Humans , Italy/epidemiology , Male , Middle Aged , No-Show Patients/psychology , No-Show Patients/statistics & numerical data , Outcome Assessment, Health Care , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Pneumonia, Viral/transmission , SARS-CoV-2 , Stomach Neoplasms/diagnosis , Stomach Neoplasms/epidemiology , Stomach Neoplasms/physiopathology , Stomach Neoplasms/psychology , Surveys and Questionnaires
2.
Dig Liver Dis ; 51(3): 375-381, 2019 03.
Article in English | MEDLINE | ID: mdl-30377063

ABSTRACT

BACKGROUND AND AIM: Endoscopic full-thickness resection(EFTR) with FTRD® in colo-rectum may be useful for several indications.The aim was to assess its efficacy and safety. MATERIAL AND METHODS: In this retrospective multicenter study 114 patients were screened; 110 (61M/49F, mean age 68 ±â€¯11 years, range 20-90) underwent EFTR using FTRD®. Indications were:residual/recurrent adenoma (39), incomplete resection at histology (R1 resection) (26), non-lifting lesion (12), adenoma involving the appendix (2) or diverticulum (2), subepithelial lesions(10), suspected T1 carcinoma (16), diagnostic resection (3). Technical success (TS: lesion reached and resected), R0 resection (negative lateral and deep margins),EFTR rate(all layers documented in the specimen) and safety have been evaluated. RESULTS: TS was achieved in 94.4% of cases. EFTR was achieved in 91% with lateral and deep R0 resection in 90% and 92%. Mean size of specimens was 20 mm (range 6-42). In residual/recurrent adenomas, final analysis revealed: low-risk T1 (11), adenoma with low-grade dysplasia (LGD) (24) and high-grade dysplasia (HGD) (3), scar tissue (1). Histology reports of R1 resections were: adenoma with LGD (6), with HGD (1), low-risk (6) and high-risk (1) T1, scar tissue (12). Non-lifting lesions were diagnosed as: adenoma with HGD (3), low-risk (7) and high risk (2) T1. Adverse clinical events occurred in 12 patients (11%),while adverse technical events in11%. Three-months follow-up was available in 100 cases and residual disease was evident in only seven patients. CONCLUSIONS: EFTR using FTRD® seems to be a feasible, effective and safe technique for treating selected colo-rectal lesions. Comparative prospective studies are needed to confirm these promising results.


Subject(s)
Adenoma/surgery , Colorectal Neoplasms/surgery , Endoscopy/instrumentation , Adult , Aged , Aged, 80 and over , Female , Humans , Italy , Male , Middle Aged , Neoplasm Staging , Recurrence , Retrospective Studies , Treatment Outcome , Young Adult
3.
Int J Immunopathol Pharmacol ; 24(4): 1017-25, 2011.
Article in English | MEDLINE | ID: mdl-22230407

ABSTRACT

Patients with chronic fatigue syndrome (CFS) often report a comorbid depressive disorder. Comorbid depression may negatively influence the long-term outcome of CFS therefore it must be correctly diagnosed and treated. The aim of the present study is to provide a clinical and psychometric assessment of CFS patients with and without depressive features. A comparative analysis between 57 CFS subjects (CDC, 1994), 17 of whom with a comorbid depression, and 55 matched healthy volunteers was assessed to evaluate the presence of any psychophysical distress and alexithymic traits, by means of Symptom Checklist-90-R (SCL-90R) and Toronto Alexithymia Scale (TAS-20). The severity of fatigue was also assessed in all CFS patients using the Fatigue Impact Scale (FIS). With regard to psychiatric comorbidity, the SCL-90R scores showed higher levels of somatic complaints in CFS patients than in healthy subjects, whereas augmented depressive and obsessive-compulsive symptoms were observed only in the depressed CFS subgroup. When comparing the TAS-20 scores, we observed a selective impairment in the capacity to identify feelings and emotions, as measured by the Difficulty in Identifying Feelings subscale (DIF), non-depressed CFS patients showing an intermediate score between depressed CFS and healthy controls. Finally, in terms of FIS scores, a statistical trend versus a higher fatigue severity in depressed CFS patients, with respect to non-depressed ones, was observed. In conclusion, comorbid depression in CFS significantly increased the level of psychophysical distress and the severity of alexithymic traits. These findings suggest an urgent need to address and treat depressive disorders in the clinical care of CFS cases, to improve social functioning and quality of life in such patients.


Subject(s)
Affective Symptoms/psychology , Depressive Disorder/psychology , Fatigue Syndrome, Chronic/psychology , Stress, Psychological/psychology , Adult , Affective Symptoms/diagnosis , Affective Symptoms/epidemiology , Analysis of Variance , Case-Control Studies , Checklist , Chi-Square Distribution , Comorbidity , Depressive Disorder/diagnosis , Depressive Disorder/epidemiology , Fatigue Syndrome, Chronic/diagnosis , Fatigue Syndrome, Chronic/epidemiology , Female , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Predictive Value of Tests , Psychiatric Status Rating Scales , Psychometrics , Severity of Illness Index , Stress, Psychological/diagnosis , Stress, Psychological/epidemiology
4.
Int J Immunopathol Pharmacol ; 23(2): 417-22, 2010.
Article in English | MEDLINE | ID: mdl-20646337

ABSTRACT

Cytokines may influence brain activities especially during stressful conditions, and elevated levels of IL-6 and C-reactive protein have been pointed out in subjects with Major Depression. If pro-inflammatory cytokines play a causative role in major depressive disorders, one would expect that antidepressants may down-regulate these cytokines or interfere with their actions, leading to improvement of depressive symptoms. Accumulating evidence has been published that antidepressants modulate cytokine production and this is particularly true for Tricyclics and Selective serotonin reuptake inhibitors (SSRIs), but the influence of newer antidepressants acting on both serotonin (5-HT) and norepinephrine (NE) such as venlafaxine, duloxetine and mirtazapine on cytokine levels has not been extensively studied. However, both pre-clinical and clinical studies examined in this review have demonstrated that newer serotonin-noradrenalin antidepressants can inhibit the production and/or release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines, suggesting that reductions in inflammation might contribute to treatment response. Moreover, the results of the present review support the notion that the serotonin-noradrenalin antidepressants venlafaxine and mirtazapine may influence cytokine secretion in patients affected by MD, restoring the equilibrium between their physiological and pathological levels and leading to recovery. To date, no studies have evaluated the effect of duloxetine, the newest serotonin-noradrenalin antidepressant, on cytokine levels and therefore this should be evaluated in future studies.


Subject(s)
Antidepressive Agents/pharmacology , Cyclohexanols/pharmacology , Cytokines/biosynthesis , Mianserin/analogs & derivatives , Thiophenes/pharmacology , Animals , Duloxetine Hydrochloride , Humans , Mianserin/pharmacology , Mirtazapine , Selective Serotonin Reuptake Inhibitors/pharmacology , Venlafaxine Hydrochloride
5.
Dig Liver Dis ; 42(2): 127-30, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19596616

ABSTRACT

BACKGROUND: Submucosal lifting of lesions prior to endoscopic resection is crucial to reduce complications and improve the technical feasibility of the procedure. AIM: To compare a self-assembled hydro-jet system vs. standard needle injection for tissue elevation prior to endoscopic resection of colorectal lesions. METHODS: Randomised study performed at a single tertiary care institution. Consecutive patients with colonoscopic diagnosis of sessile polyps or non-polypoid lesions >5 mm or laterally spreading tumours. OUTCOME MEASURES: successful elevation, time to proper elevation, completeness of excision, cautery damage, and general histological diagnostic quality (blinded pathologic assessment). RESULTS: 79 patients were randomised to hydro-jet (40 patients, group A) and needle (39 patients, group B) elevation. Successful elevation was achieved in 97.5% and 94.8%, respectively. Time to proper elevation was 8+/-5 s vs. 18+/-3 s (p<0.05). In group A, histology showed selective accumulation of fluid in the submucosa with intact collagen fibres. Damage to muscularis mucosa was never noted in the specimens of group A and in 7 cases of group B (p<0.01). Artefacts from "cautery effect" were very limited. Radial margins of resection could be adequately evaluated in all cases and were negative. CONCLUSIONS: The hydro-jet system is as effective and safe as standard needle injection for tissue elevation prior to endoscopic resection of colorectal lesions, but it is significantly faster.


Subject(s)
Ablation Techniques/instrumentation , Colonic Polyps/surgery , Colonoscopy/methods , Colorectal Neoplasms/surgery , Precancerous Conditions/surgery , Ablation Techniques/methods , Aged , Biopsy/instrumentation , Female , Humans , Male , Middle Aged
6.
J Biol Regul Homeost Agents ; 23(3): 133-40, 2009.
Article in English | MEDLINE | ID: mdl-19828089

ABSTRACT

The individuation of sensitive and specific biochemical markers, easily assessable on large samples of subjects and usefully employable as predictors of severe psychiatric disorders, such as mood disorders, could help clinicians to improve the diagnostic and therapeutic processes facilitating the long-term follow-up. In particular, serum cholesterol levels may potentially be optimal markers due to their relative easy sampling and low cost. The involvement of cholesterol in affective disorders such as Major Depression (MD), Seasonal Affective Disorder (SAD) and Bipolar Disorders (BD) is a debated issue in current research. However, current literature is controversial and, to date, it is still not possible to reach an agreement on its possible usefulness of cholesterol as a biological marker of affective disorders. Despite the controversial results on the relationships between cholesterol levels and affective disorders, the majority of literature seems to show a more consistent relationship between cholesterol levels and suicidal behaviour, with few studies that have found no relationships. The aim of this review is to elucidate current facts and views about the role of cholesterol levels in mood disorders as well as its involvement in suicidal behaviour.


Subject(s)
Cholesterol/blood , Mood Disorders/blood , Suicide , Bipolar Disorder/blood , Depression/blood , Humans , Seasonal Affective Disorder/blood
7.
Dig Liver Dis ; 41(10): 729-34, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19362522

ABSTRACT

BACKGROUND: Acrylate glue injection is seldom performed in patients with bleeding oesophageal varices. AIM: To assess efficacy and safety of acrylate glue injection in patients with bleeding oesophageal varices, as well as the impact of this technique on subsequent variceal ligation. METHODS: Prospective study on 133 consecutive cirrhotic patients treated by intravariceal injection of undiluted N-butyl-2-cyanoacrylate into the bleeding varix. Outcome measures were initial haemostasis, recurrent bleeding, complications and mortality at 6 weeks. RESULTS: 52 patients were actively bleeding at endoscopy and 81 showed stigmata of recent haemorrhage. Initial haemostasis was achieved in 49/52 active bleeders (94.2% [95% CI 85.1-98.5]). Overall, early recurrent bleeding occurred in 7 patients (5.2% [95% CI 2.3-10.1]). No major procedure-related complication was recorded. At 6 weeks, death occurred in 11 patients, with an overall bleeding-related mortality of 8.2% [95% CI 5.8-15.3]. Mortality was higher in active (15.4% [95% CI 6.9-28.1]) than non-active bleeders (3.7% [95% CI 0.8-10.4], OR 4.7 [95% CI 1.05-28.7], p=0.02). Of those surviving the first bleeding episode, 112 patients subsequently underwent ligation. No technical difficulties were encountered in performing the banding procedure which was successfully completed in all cases. CONCLUSIONS: Emergency injection of acrylate glue is safe and effective for the treatment of acute bleeding oesophageal varices and does not hamper subsequent variceal ligation.


Subject(s)
Cyanoacrylates/administration & dosage , Esophageal and Gastric Varices/therapy , Gastrointestinal Hemorrhage/therapy , Hemostasis, Endoscopic/methods , Tissue Adhesives/administration & dosage , Acute Disease , Aged , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/diagnosis , Esophageal and Gastric Varices/mortality , Esophagoscopy/methods , Female , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/mortality , Humans , Injections, Intralesional , Ligation , Male , Middle Aged , Prospective Studies , Recurrence , Treatment Outcome
8.
Dig Liver Dis ; 41(7): e42-4, 2009 Jul.
Article in English | MEDLINE | ID: mdl-18799375

ABSTRACT

Ulcerative colitis may be associated with a number of skin lesions such as erythema nodosum and pyoderma gangrenosum. We here describe an unusual case of a 33-year-old-caucasian male with ulcerative colitis and skin lesions diagnosed as leukocytoclastic vasculitis. An initial treatment with oral deflazacort led to little benefit, while treatment with oral mesalazine caused remission of the skin and intestinal manifestations in 2 weeks.


Subject(s)
Colitis, Ulcerative/complications , Colitis, Ulcerative/diagnosis , Vasculitis, Leukocytoclastic, Cutaneous/complications , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Colitis, Ulcerative/drug therapy , Humans , Male , Mesalamine/therapeutic use , Vasculitis, Leukocytoclastic, Cutaneous/drug therapy , Vasculitis, Leukocytoclastic, Cutaneous/pathology
9.
J Biol Regul Homeost Agents ; 22(3): 195-200, 2008.
Article in English | MEDLINE | ID: mdl-18842173

ABSTRACT

The aim of the present study is to evaluate role of plasma antioxidants (albumin, bilirubin and uric acid) in patients suffering from type I Bipolar Disorder (BD-I) during different phases of illness: acute mania, euthymia and bipolar depression. Medical records of consecutive 110 BD-I patients (38 patients with acute mania, 35 in euthymic state, full remission, and 37 in depressive phase) were reviewed to evaluate plasma antioxidant levels. Laboratory data of 40 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. Serum uric acid levels were higher in acute mania than other patient subgroups and healthy controls. Serum uric acid levels directly correlated with BRMRS and YMRS scores. No differences were found between clinical groups during different phases and healthy controls concerning albumin and bilirubin. In conclusion, the results of the present study support the notion that serum uric acid levels may be higher in patients with BP-I (especially during manic phases) which may suggest a dysregulation of the purinergic system. However, limitations should be considered and further studies are needed.


Subject(s)
Antioxidants/metabolism , Bipolar Disorder/blood , Bipolar Disorder/psychology , Adult , Bipolar Disorder/classification , Female , Humans , Male
11.
J Clin Pathol ; 61(10): 1112-5, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18755715

ABSTRACT

OBJECTIVES: Helicobacter pylori infection is a major health problem worldwide, and effective eradication of the infection is mandatory. The efficacy of recommended eradication regimens is approximately 70%. To avoid treatment failure and the consequent development of secondary resistance(s), it is important to choose the most appropriate first-line treatment regimen. This choice should also be made based on the knowledge of the antimicrobial resistance peculiar to a given geographical area. We evaluated the prevalence of antimicrobial-resistant H pylori strains isolated from naive patients and from patients with previous unsuccessful treatments. METHODS: This study examined 109 H pylori-infected subjects (Group 1) who had never received an eradication treatment and 104 H pylori-infected subjects (Group 2) who had failed one or more eradication treatments. Resistance to amoxicillin (AMO), tetracycline (TET), clarithromycin (CLA), metronidazole (MET) and levofloxacin (LEV) was determined using the epsilometer test. The significance of differences was evaluated by the chi2 test. RESULTS: The prevalence of antimicrobial resistance was 0% versus 3.1% to AMO, 0% versus 2% to TET, 27% versus 41.3% to MET (p<0.05), 18% versus 45.8% to CLA (p<0.05) and 3% versus 14.6% to LEV (p<0.05) in Group 1 vs Group 2, respectively. In Group 2, there was an increased prevalence of H pylori strains resistant to multiple antimicrobials. CONCLUSIONS: This study confirms the high prevalence of H pylori strains resistant to CLA and MET, and indicates that unsuccessful treatments significantly increase resistance. Choosing eradication regimens other than standard triple therapy as a first-line therapy should be advisable in areas with high primary antimicrobial resistance prevalence.


Subject(s)
Drug Resistance, Bacterial , Helicobacter Infections/microbiology , Helicobacter pylori/drug effects , Adult , Aged , Amoxicillin , Anti-Bacterial Agents/therapeutic use , Case-Control Studies , Chi-Square Distribution , Clarithromycin , Colony Count, Microbial , Female , Helicobacter Infections/drug therapy , Helicobacter pylori/isolation & purification , Helicobacter pylori/physiology , Humans , Levofloxacin , Male , Metronidazole , Middle Aged , Ofloxacin , Tetracycline Resistance , Treatment Failure
12.
Int J Immunopathol Pharmacol ; 21(2): 319-24, 2008.
Article in English | MEDLINE | ID: mdl-18547475

ABSTRACT

The aim of the present study is to evaluate the role of CRP and Total Cholesterol (TC) in patients suffering from type I Bipolar Disorder (BD-I). Moreover, the goal is to elucidate possible CRP and TC differences in different phases of BD-I: acute mania, euthymia and bipolar depression. Medical records of 90 BD-I patients (30 patients with acute mania, 30 in euthymic state, full remission, and 30 in depressive phase) were reviewed to evaluate serum CRP and TC levels. Laboratory data of 30 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. CRP levels were higher in acute mania and depressive phase subgroups when compared to healthy controls. CRP was positively associated with BRMRS and YMRS scores in acute mania and with HAM-D in depressive phase subgroups. TC levels were lower in all clinical groups compared to controls. TC levels were negatively correlated to BRMRS, YMRS and HAM-D. In conclusion, the results of the present study support the notion that CRP and TC may be altered in patients with BP-I.


Subject(s)
Bipolar Disorder/blood , C-Reactive Protein/metabolism , Cholesterol/blood , Adiposity , Adolescent , Adult , Bipolar Disorder/psychology , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Retrospective Studies
14.
Int J Immunopathol Pharmacol ; 19(4): 721-5, 2006.
Article in English | MEDLINE | ID: mdl-17166394

ABSTRACT

Recently, a possible relationship between C-Reactive Protein (CRP), a marker of underlying low-grade inflammation, and mood disorders has been proposed by some researchers. The aim of this review is to elucidate the current facts and views about CRP in mood disorders such as Depressive and Bipolar Disorders. Several studies have examined the relationship between affective disorders and CRP, but the majority of the studies in literature have been limited by retrospective, case-controlled study design, and very few studies have examined the relationship between depression and CRP in large study samples. In conclusion, the role of CRP in mood disorders is, to date, intriguing but somewhat unclear. Further prospective studies are needed to introduce the CRP in clinical settings as a marker of affective states and suicidability.


Subject(s)
C-Reactive Protein/physiology , Mood Disorders/physiopathology , Humans
16.
Int J Immunopathol Pharmacol ; 18(1): 15-9, 2005.
Article in English | MEDLINE | ID: mdl-15698507

ABSTRACT

Cannabinoids are the constituents of the marijuana plants. The central effects of exogenous cannabinoids are implicated in enhancing mood, altering emotional states, and interfering in the formation of short-term memory. Cannabinoid receptors are G protein-coupled receptors with seven transmembrane domains that are expressed on the cell surface with their binding domain exposed to the extracellular space. To date, two cannabinoid receptors have been cloned, CB1 and CB2. Recent evidence suggests that a third CB3 receptor is out there, waiting to be cloned. The endocannabinoids may represent the first members of a new classes of neuromodulators, that are not stored in cell vesicles, but rather synthesised by the cell on demand. The endogenous cannabinoid system could play a central role in several neuropsychiatric disorders and is also involved in other conditions such as pain, spasticity and neuroprotection. Implication of cannabinoid system in the pathogenesis and development of schizophrenia is also discussed.


Subject(s)
Mental Disorders/metabolism , Nervous System Diseases/metabolism , Receptors, Cannabinoid/metabolism , Humans , Mental Disorders/psychology , Nervous System Diseases/psychology , Receptors, Cannabinoid/genetics , Receptors, Cannabinoid/physiology , Schizophrenia/etiology
17.
Int J Immunopathol Pharmacol ; 18(4): 737-44, 2005.
Article in English | MEDLINE | ID: mdl-16388723

ABSTRACT

Hypothalamic pituitary thyroid (HPT) axis abnormalities and alterations in major depression are reported in the literature. The aim of our study was to evaluate the effect of mirtazapine on thyroid hormones after 6 months of therapy in a sample of adult outpatients with Major Depression (MD). 17 adult outpatients (7 men, 10 women) with MD according to DSM-IV criteria, were included in the study. All participants had to have met criteria for a major depressive episode with a score of at least 15 on the Hamilton Depression Rating Scale (HAM-D). Fasting venous blood samples were obtained for determination of serum Thyroid Stimulating Hormone (TSH), Free T3 (FT3) and Free T4 (FT4) concentrations both at baseline and after 6 months of therapy. HAM-D scores decreased significantly from the first day of treatment to the end of the treatment period (P<0.001) and twelve patients (70.6%) were classified as responders. A significant increase in FT3 concentrations was found between baseline and the end of the treatment period (P=0.015), whereas FT4 concentrations decreased (P=0.046). No significant changes were found in TSH levels. Higher FT4 concentrations at baseline predicted higher HAM-D scorers both at baseline and at the end of the treatment period. Furthermore, higher FT3 concentrations at endpoint were found to be predictors of lower HAM-D scores. Long-term treatment with mirtazapine increases FT3 levels and decreases FT4 maybe involving the deiodination process of T4 into T3.


Subject(s)
Antidepressive Agents, Tricyclic/adverse effects , Depressive Disorder, Major/blood , Mianserin/analogs & derivatives , Thyroid Hormones/blood , Adult , Antidepressive Agents, Tricyclic/therapeutic use , Depressive Disorder, Major/drug therapy , Female , Humans , Hypothalamo-Hypophyseal System/drug effects , Male , Mianserin/adverse effects , Mianserin/therapeutic use , Middle Aged , Mirtazapine , Psychiatric Status Rating Scales , Regression Analysis , Thyroid Gland/drug effects , Thyrotropin/blood , Thyroxine/blood , Treatment Outcome , Triiodothyronine/blood
19.
Mol Cell Endocrinol ; 198(1-2): 69-75, 2002 Dec 30.
Article in English | MEDLINE | ID: mdl-12573816

ABSTRACT

Prostate growth and differentiation is under the control of androgens not only during fetal life and childhood but also in adulthood, and it has been proposed that increased prostatic concentration of androgens, or increased androgen responsiveness, causes benign prostatic hyperplasia (BPH). However, different androgen ablation strategies such as treatment with GnRH agonists and finasteride resulted in a modest decrease of the hyperplastic prostate volume. In the last few years it became evident that both androgen-dependent and androgen-independent growth factors promote prostate enlargement by inducing cell proliferation or reducing apoptosis. Therefore, new therapeutic strategies, aimed at reducing intraprostatic growth factor signaling, are under investigation. In this study, we report further evidence that a non hypercalcemic-analogue of vitamin D(3), analogue (V) decreases growth factor-induced human BPH cell proliferation and survival. We found that Des (1-3) insulin-like growth factor [Des (1-3) IGF-I], an IGF-I analogue, which does not bind to IGF-binding proteins, is a potent mitogen for BPH stromal cells via a dual mechanism: stimulation of cell growth and inhibition of apoptosis. Similar results were previously reported for another growth factor for BPH cells, keratinocyte growth factor (KGF). Accordingly, we speculate that both KGF and IGF might be involved in the pathogenesis of BPH. We also found analogue (V) not only inhibits the mitogenic activity of growth factors on BPH cells, but even decreased the basal expression of bcl-2, and induced apoptosis. Therefore, vitamin D(3) analogues might be considered for the medical treatment of BPH.


Subject(s)
Cholecalciferol/analogs & derivatives , Cholecalciferol/pharmacology , Insulin-Like Growth Factor I/pharmacology , Peptide Fragments/pharmacology , Prostatic Hyperplasia/pathology , Stromal Cells/physiology , Animals , Apoptosis , Cell Division , Cells, Cultured , Cholecalciferol/metabolism , Cholecalciferol/therapeutic use , Humans , Insulin-Like Growth Factor I/metabolism , Male , Peptide Fragments/metabolism , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Stromal Cells/pathology
20.
J Clin Endocrinol Metab ; 85(7): 2576-83, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10902811

ABSTRACT

Prostate enlargement and function is under the dual control of androgens and intraprostatic growth factors. They regulate, in concert, prostate cell proliferation and apoptosis. An increased signaling of both growth factors and androgens are supposed to underlie benign prostate hyperplasia (BPH), one of the more common disorders of the aging male. Since, in clinical practice, androgen ablation resulted in a rather limited decrease in prostate volume, therapeutic strategies targeting intraprostatic growth factors are emerging. The activated form of vitamin D, vitamin D3, and some of its analogues have been described as potent regulators of cell growth and differentiation. In this study, we report the effects of one of these vitamin D3 analogues, 1,25-dihydroxy-16ene-23yne D3, or analogue (V), on the fate of isolated epithelial cells derived from patients with BPH. We essentially found that analogue (V), as well as vitamin D3, inhibited BPH cell proliferation and counteracted the mitogenic activity of a potent growth factor for BPH cells, such as keratinocyte growth factor (KGF). Moreover, analogue (V) induced bcl-2 protein expression, intracellular calcium mobilization, and apoptosis in both unstimulated and KGF-stimulated BPH cells. Since a short-term (5-min) incubation with analogue (V) reduced the KGF-induced tyrosine phosphorylation of a 120-kDA protein, corresponding to the KGF receptor, a rapid and direct cross-talk between these two molecules is suggested. Such a rapid effect of analogue (V), together with the transient induction of intracellular calcium waves, seems to indicate the partial involvement of a membrane, nongenomic receptor for vitamin D3. In conclusion, we demonstrated the antiproliferative and proapoptotic effect of analogue (V) in BPH cells and speculated on its possible use in the therapy of BPH.


Subject(s)
Calcitriol/analogs & derivatives , Cholecalciferol/analogs & derivatives , Fibroblast Growth Factors , Growth Substances/pharmacology , Keratinocytes/drug effects , Prostatic Hyperplasia/pathology , Receptors, Fibroblast Growth Factor , Blotting, Western , Calcitriol/pharmacology , Calcium/metabolism , Cell Death/drug effects , Cell Division/drug effects , Electrophoresis, Polyacrylamide Gel , Fibroblast Growth Factor 10 , Fibroblast Growth Factor 7 , Humans , Immunohistochemistry , Male , Microscopy, Electron , Phosphorylation , Primed In Situ Labeling , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins c-bcl-2/genetics , Receptor, Fibroblast Growth Factor, Type 2 , Receptors, Growth Factor/drug effects , Tyrosine/metabolism
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