Biomedical subjects

Vassilios Papadopoulos

Publications and source records attributed to Vassilios Papadopoulos.

At least 19 recordsLinked to original sources

PubMed2006

The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria.

The peripheral-type benzodiazepine receptor (PBR) is an 18 kDa mitochondrial membrane protein with still elusive function in cell death. Here, we studied whether PBR is involved in Ca2+-induced permeability transition pore (PTP) opening in isolated rat brain mitochondria (RBM). PTP opening is important in mitochondrial events leading to programmed cell death. Immunoblots revealed a single 18 kDa anti-PBR antibody-immunoreactive band in purified RBM. Adenine nucleotide transporter, a key PTP component, was found in the PBR-immunoprecipitate. In isolated intact RBM, addition of a specific anti-PBR antibody [H. Li, Z. Yao, B. Degenhardt, G. Teper, V. Papadopoulos, Cholesterol binding at the cholesterol recognition/interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide, Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 1267-1272] delayed Ca2+-induced dissipation of membrane potential (psi(m)) and diminished cyclosporine A-sensitive Ca2+ efflux, which are both indicative for the suppression of PTP opening. Moreover, anti-PBR antibody caused partial retention of Ca2+ in the mitochondrial matrix in spite of psi(m) dissipation, and reduced activation of respiratory rate at Ca2+-induced PTP opening. A release of pro-apoptotic factors, AIF and cytochrome c, from RBM was shown at threshold Ca2+ load. Anti-PBR antibody blocked the release of AIF but did not affect the cytochrome c release. Addition of ATP was able to initiate PTP closing, associated with psi(m) restoration and Ca2+ re-accumulation. At the same time mitochondrial protein phosphorylation (incorporation of 32P from [gamma-32P]ATP) occurred and anti-PBR antibody was able to inhibit phosphorylation of these proteins. The endogenous PBR ligand, protoporphyrin IX, facilitated PTP opening and phosphorylation of the mitochondrial proteins, thus, inducing effects opposite to anti-PBR antibody. This study provides evidence for PBR involvement in PTP opening, controlling the Ca2+-induced Ca2+ efflux, and AIF release from mitochondria, important stages of initiation of programmed cell death.

Adenosine Triphosphate↗

PubMed2006

Advances in liver echinococcosis: diagnosis and treatment.

Echinococcosis or hydatid cyst disease is a zoonosis caused by the larval cestode Echinococcus granulosus. It consists of a parasitic tapeworm disease affecting mainly liver. Nevertheless, the disease might well spread to more unusual sites such as lungs and brain. The definitive diagnosis of liver echinococcosis requires a combination of imaging, serologic, and immunologic studies. Despite the fact that a number of scolecoidal agents have been developed against liver hydatid disease, the cornerstone of the definitive treatment remains surgery. Both the classic surgical techniques and the recently developed minimally invasive and laparoscopic methods target the eradication of the disease by simultaneously avoiding perioperative spillage and dissemination or recurrence of echinococcosis. The present article constitutes a review of the biology of the parasite as well as the epidemiology, diagnosis, and therapeutic options of the liver hydatid disease.

Algorithms↗

PubMed2006

Peripheral-type benzodiazepine receptor overexpression and knockdown in human breast cancer cells indicate its prominent role in tumor cell proliferation.

The peripheral-type benzodiazepine receptor (PBR), an 18-kDa high affinity drug and cholesterol binding protein, is expressed at high levels in various cancers. Its expression is positively correlated with aggressive metastatic behavior in human breast cancer cells. To determine the role of PBR in tumor progression, two human mammary carcinoma cell lines were utilized: the non-aggressive MCF-7 cell line, which expresses extremely low PBR levels, and the highly aggressive MDA-MB-231 cell line, which has much higher PBR levels. We have generated stably transfected lines of the tetracycline-repressible MCF-7 cell line (MCF-7 Tet-Off) with inducible human PBR cDNA. Induction of PBR expression in MCF-7 Tet-Off cells increased PBR ligand binding and cell proliferation. Transfection of MDA-MB-231 cells with multiple siRNAs complementary to PBR (PBR-siRNAs) led to different levels of PBR mRNA knockdown. Lentiviral-mediated PBR RNA interference in MDA-MB-231 cells decreased PBR levels by 50%. Decreased PBR expression was associated with cell cycle arrest at G2 phase, decreased cell proliferation, and significant increases in the protein levels of the cyclin-dependent kinase inhibitor p21(WAF/CIP1). These changes were accompanied by p53 activation seen as increased p53 phosphorylation (Ser15). In parallel, increased proteolytic activation of caspase-3 was also observed. Taken together these results suggest that PBR protein expression is directly involved in regulating cell survival and proliferation in human breast cancer cells by influencing signaling mechanisms involved in cell cycle control and apoptosis.

Apoptosis↗

PubMed2006

Protein-protein interactions mediate mitochondrial cholesterol transport and steroid biosynthesis.

Transport of cholesterol into the mitochondria is the rate-determining, hormone-sensitive step in steroid biosynthesis. Here we report that the mechanism underlying mitochondrial cholesterol transport involves the formation of a macromolecular signaling complex composed of the outer mitochondrial membrane translocator protein (TSPO), previously known as peripheral-type benzodiazepine receptor; the TSPO-associated protein PAP7, which binds and brings to mitochondria the regulatory subunit RIalpha of the cAMP-dependent protein kinase (PKARIalpha); and the hormone-induced PKA substrate, steroidogenic acute regulatory protein (StAR). Hormone treatment of MA-10 Leydig cells induced the co-localization of TSPO, PAP7, PKARIalpha, and StAR in mitochondria, visualized by confocal microscopy, and the formation in living cells of a high molecular weight multimeric complex identified using photoactivable amino acids. The hormone-induced recruitment of exogenous TSPO in this complex was found to parallel the increased presence of 7-azi-5alpha-cholestan-3beta-ol in the samples. Co-expression of Tspo, Pap7, PkarIalpha, and Star genes resulted in the stimulation of steroid formation in both steroidogenic MA-10 and non-steroidogenic COS-F2-130 cells that were engineered to metabolize cholesterol. Disruption of these protein-protein interactions and specifically the PKARIalpha-PAP7 and PAP7-TSPO interactions, using PAP7 mutants where the N0 area homologous to dual A-kinase-anchoring protein-1 or the acyl-CoA signature motif were deleted or using the peptide Ht31 known to disrupt the anchoring of PKA, inhibited both basal and hormone-induced steroidogenesis. These results suggest that the initiation of cAMP-induced protein-protein interactions results in the formation of a multivalent scaffold in the outer mitochondrial membrane that mediates the effect of hormones on mitochondrial cholesterol transport and steroidogenesis.

Animals↗

PubMed2006

3D QSAR studies of AChE inhibitors based on molecular docking scores and CoMFA.

Three-dimensional quantitative structure-activity relationship (3D QSAR) studies were performed on acetylcholinesterase (AChE) inhibitors, based on molecular docking scores obtained by using FlexX and FlexiDock and comparative molecular field analysis (CoMFA). The docking scores were used as molecular descriptors along with the steric and electrostatic field values of CoMFA, for partial least square (PLS) analysis. The high leave one out (LOO) cross-validated correlation coefficient (q(2)=0.714) reveals that the model is a useful tool for the prediction of test set as well as newly designed structures against AChE activity. The superimposed CoMFA models on the receptor site of AChE are guiding the design of potential inhibitory structures directed against AChE activity.

Acetylcholinesterase↗

PubMed2006

Cloning, sequencing, and chromosomal localization of pig peripheral benzodiazepine receptor: three different forms produced by alternative splicing.

We report the molecular cloning of the cDNA sequence for pig peripheral benzodiazepine receptor (PBR) by using RT-PCR and 5'/3' terminal extension. Three different transcripts (long, middle, and short) are identified. The open reading frame (ORF) of the longest PBR mRNA encodes a deduced polypeptide of 169 amino acids with a calculated molecular weight of 18,609 Da and an estimated pI of 9.70, which corresponds to the authentic PBR of other mammalian species. The middle transcript (PBR-M) contains a 141-codon ORF, which is consistent with that of the authentic PBR, but lacks a region of 84 bp so that its encoded polypeptide lacks a region of 28 amino acids from 35 to 62 of the authentic PBR polypeptide. The short transcript (PBR-S) contains a 104-codon ORF, which overlaps that of the authentic PBR, but lacks a region of 211 bp so that its encoded polypeptide lacks a region of 65 amino acids of the N-terminal of the authentic PBR. The pig PBR gene was mapped to the telomeric end of SSC5p. In addition, PBR mRNA was the more abundant detected form in pig tissues and in warm kidney that underwent ischemia suggesting functional implications of PBR during the renal repair process.

Adrenal Glands↗

PubMed2006

NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexras1.

Dexras1 is a 30 kDa G protein in the Ras subfamily whose discovery was based on its pronounced inducibility by the glucocorticoid dexamethasone. It binds to neuronal nitric oxide synthase (nNOS) via the adaptor protein CAPON, eliciting S-nitrosylation and activation of Dexras1. We report that Dexras1 binds to the peripheral benzodiazepine receptor-associated protein (PAP7), a protein of unknown function that binds to cyclic AMP-dependent protein kinase and the peripheral benzodiazepine receptor. PAP7 in turn binds to the divalent metal transporter (DMT1), an iron import channel. We have identified a signaling cascade in neurons whereby stimulation of NMDA receptors activates nNOS, leading to S-nitrosylation and activation of Dexras1, which, via PAP7 and DMT1, physiologically induces iron uptake. As selective iron chelation prevents NMDA neurotoxicity in cortical cultures, the NMDA-NO-Dexras1-PAP7-DMT1-iron uptake signaling cascade also appears to mediate NMDA neurotoxicity.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Modulation of peripheral-type benzodiazepine receptor during ischemia reperfusion injury in a pig kidney model: a new partner of leukemia inhibitory factor in tubular regeneration.

BACKGROUND: It was demonstrated that postischemic kidney expresses different factors in a pattern that recapitulates expression of these factors in the developing kidney. We investigated whether peripheral-type benzodiazepine receptor (PBR), which belongs to the mitochondrial permeability transition pore and is essential during development, could be influenced by the ischemia-reperfusion injury process when compared with leukemia inhibitor factor (LIF). STUDY DESIGN: PBR, LIF, and LIF receptor messengers and proteins were analyzed in adult normal and ischemic kidney under conditions mimicking cardiac arrest: 18 pigs were studied after 60 minutes of warm ischemia and reperfusion for 7 days and compared with sham-operated (Sham, n = 12) and control (CONT, n = 12) groups. The same messengers and proteins were assessed in fetal kidneys. RESULTS: In normal kidney, PBR was expressed in descending and ascending limbs of Henle and in distal tubules. After ischemia-reperfusion injury, PBR mRNA significantly increased between days 1 and 7 in cortex and outer medulla. PBR protein increased between days 1 and 7, and was transiently expressed in proximal tubules at days 1 and 3 and returned to basal level at day 7. LIF messenger and protein increased rapidly at day 1 in proximal tubules. In turn, LIF receptor messenger and protein were not changed during reperfusion. CONCLUSIONS: These results suggest that PBR may be implicated in ischemia-reperfusion injury and, particularly, in the regenerative process within proximal tubules with LIF. These new insights open the possibility of novel targets for organ protection and repair.

Animals↗

PubMed2006

Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function.

The peripheral-type benzodiazepine receptor or recognition site (PBR) is a widely distributed transmembrane protein that is located mainly in the outer mitochondrial membrane. The PBR binds to high-affinity drug ligands and cholesterol. Many functions are associated directly or indirectly with the PBR, including the regulation of cholesterol transport and the synthesis of steroid hormones, porphyrin transport and heme synthesis, apoptosis, cell proliferation, anion transport, regulation of mitochondrial functions and immunomodulation. Based on these functions, there are many potential clinical applications of PBR modulation, such as in oncologic, endocrine, neuropsychiatric and neurodegenerative diseases. Although "PBR" is a widely used and accepted name in the scientific community, recent data regarding the structure and molecular function of this protein increasingly support renaming it to represent more accurately its subcellular role (or roles) and putative tissue-specific function (or functions). Translocator protein (18kDa) is proposed as a new name, regardless of the subcellular localization of the protein.

Animals↗

PubMed2006

Incarcerated Spigelian hernia: a case report.

BACKGROUND: Spigelian hernia is a rare partial abdominal wall defect in the transversus abdominus aponeurosis or Spigelian fascia. We here report the case of a patient with incarcerated greater omentum in a Spigelian hernia. CASE REPORT: The patient presented with a six-hour history of nausea, constant abdominal pain, and a palpable mass in the left lower quadrant. Abdominal computed tomography revealed that omentum was strangulated in a Spigelian hernia that was successfully treated by plug and mesh repair. No recurrence has been observed during three-year follow-up. CONCLUSIONS: In our case, plug and mesh repair was a safe and effective method of repairing an incarcerated Spigelian hernia with durability through three years of follow-up.

Female↗

PubMed2006

The spirostenol (22R, 25R)-20alpha-spirost-5-en-3beta-yl hexanoate blocks mitochondrial uptake of Abeta in neuronal cells and prevents Abeta-induced impairment of mitochondrial function.

Abeta(1-42) has been shown to uncouple the mitochondrial respiratory chain and promote the opening of the membrane permeability transition (MPT) pore, leading to cell death. We have previously reported that the spirostenol derivative (22R, 25R)-20alpha-spirost-5-en-3beta-yl hexanoate (SP-233) protects neuronal cells against Abeta(1-42) toxicity by binding to and inactivating the peptide. Picomolar concentrations of Abeta(1-42) decreased the mitochondrial respiratory coefficient in mitochondria isolated from the rat forebrain, and this decrease was partially reversed by SP-233. SP-233 abolished the uncoupling of oxidative phosphorylation induced by carbonyl cyanide 3-chlorophenylhydrazone on isolated mitochondria. These results are consistent with a direct effect of SP-233 on the MPT. Moreover, SP-233 displayed a neuroprotective effect on SK-N-AS human neuroblastoma cells treated with the MPT promoter, phenylarsine oxide. Treatment of SK-N-AS cells with Abeta(1-42) resulted in an accumulation of the peptide in the mitochondrial matrix; SP-233 completely scavenged Abeta(1-42) from the matrix. In addition, SP-233 protected the cells against mitochondrial toxins targeting complexes IV and V of the respiratory chain. These results indicate that Abeta(1-42) and SP-233 exert direct effects on mitochondrial function and SP-233 protects neuronal cells against Abeta-induced toxicity by targeting Abeta directly.

Adenosine Triphosphatases↗

PubMed2006

In search of rat stem Leydig cells: identification, isolation, and lineage-specific development.

Leydig cells (LCs) are thought to differentiate from spindle-shaped precursor cells that exhibit some aspects of differentiated function, including 3beta-hydroxysteroid dehydrogenase (3betaHSD) activity. The precursor cells ultimately derive from undifferentiated stem LCs (SLCs), which are postulated to be present in testes before the onset of precursor cell differentiation. We searched for cells in the neonatal rat testis with the abilities to: (i) proliferate and expand indefinitely in vitro (self renew); (ii) differentiate (i.e., 3betaHSD and ultimately synthesize testosterone); and (iii) when transplanted into host rat testes, colonize the interstitium and subsequently differentiate in vivo. At 1 week postpartum, spindle-shaped cells were seen in the testicular interstitium that differed from the precursor cells in that they were 3betaHSD-negative, luteinizing hormone (LH) receptor (LHR)-negative, and platelet-derived growth factor receptor alpha (PDGFR alpha)-positive. These cells were purified from the testes of 1-week-old rats. The cells contained proteins known to be involved in LC development, including GATA4, c-kit receptor, and leukemia inhibitory factor receptor. The putative SLCs expanded over the course of 6 months while remaining undifferentiated. When treated in media that contained thyroid hormone, insulin-like growth factor I, and LH, 40% of the putative SLCs came to express 3betaHSD and to synthesize testosterone. When transplanted into host rat testes from which LCs had been eliminated, the putative SLCs colonized the interstitium and subsequently expressed 3betaHSD, demonstrating their ability to differentiate in vivo. We conclude that these cells are likely to be the sought-after SLCs.

3-Hydroxysteroid Dehydrogenases↗

PubMed2006

Diazepam effects on carrageenan-induced inflammatory paw edema in rats: role of nitric oxide.

High doses of diazepam (10.0-20.0 mg/kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenan administration. This effect was attributed to an action of diazepam on the peripheral-type benzodiazepine receptor (PBR) present in the adrenal and/or immune/inflammatory cells. The present study was undertaken to analyze the involvement of nitric oxide (NO) on the effects of diazepam on carrageenan-induced paw edema in rats (CIPE) and to look for the presence of PBR and inducible/constitutive NO synthases (NOS) on slices taken from the inflamed paws of diazepam-treated rats. For that, an acute inhibition of NO biosynthesis was achieved using 50.0 mg/kg No mega-nitro-L-arginine (L-NAME), L-arginine (300.0 mg/kg), the true precursor of NO, and D-arginine (300.0 mg/kg), its false substrate, were also used. The following results were obtained: (1) diazepam (10.0 and 20.0 mg/kg) decreased CIPE values in a dose- and time-dependent way; (2) diazepam effects on CIPE were increased by L-NAME pretreatment; (3) treatment with L-arginine but not with D-arginine reverted at least in part the decrements of CIPE values observed after diazepam administration; (4) PBR were found in endothelial and inflammatory cells that migrated to the inflammatory site at the rat paw; (5) confocal microscopy showed the presence of both PBR and NOS in endothelial and inflammatory cells taken from inflamed paw tissues of rats treated with diazepam a finding not observed in tissues provided from rats treated with diazepam's control solution. These results suggest an important role for NO on the effects of diazepam on CIPE. Most probably, these effects reflect a direct action of diazepam on PBR present in the endothelium of the microvascular ambient and/or on immune/inflammatory cells. An action like that would lead, among other factors, to a decrease in NO, generated by NO synthase, and thus in the mechanisms responsible for CIPE.

Animals↗

PubMed2006

Increased frequency of mutations in the gene responsible for familial Mediterranean fever (MEFV) in a cohort of patients with ulcerative colitis: evidence for a potential disease-modifying effect?

The MEFV gene, responsible for familial Mediterranean fever (FMF), is involved in inflammatory reactions through altered leukocyte apoptosis, secretion of interleukin (IL)-1beta, and activation of the NF-kappa B pathway. Ulcerative Colitis (UC) and FMF are both characterized by a recurrent pattern of presentation with periods of remission and flares associated with neutrophilic infiltration at the site of injury. The aim of this study was to investigate the possible correlation between UC and MEFV gene alterations. Twenty-five consecutive, first-diagnosed and untreated UC patients, 28 control patients with rheumatoid arthritis, and 65 normal individuals were analyzed. Nonisotopic RNase Cleavage Assay (NIRCA) was applied as a first-step mutational screening method of exons 10 and 2 of MEFV gene; direct sequencing was subsequently performed to confirm the results. MEFV mutations were identified in 7 (3 M694V/0, 2 M680I/0, 1 E148Q/E148Q, and 1 A744S/0) out of 25 UC patients versus 1 (M694V/0) out of 28 rheumatoid arthritis patients (P = .0199) and 1 (M694V/0) out of 65 healthy controls (P = .0004). Four out of 7 patients with MEFV mutations had inflammatory arthritis, a clinical finding that was not observed in the 18 UC patients with unmutated MEFV (P = .0028). Patients with UC almost universally carried the T A C G MEFV exon 2 haplotype in contrast with normal individuals (P < .0001) and FMF patients (P = .0310). In conclusion the increased frequency of mutations of MEFV in UC patients, especially in those with episodic arthritis, suggests a possible modifying effect of MEFV in the disease process and its localization within the joint. The difference in distribution of MEFV exon 2 haplotypes between UC patients and both FMF patients and normal individuals, suggests that UC patients constitute a genetically distinct population. Larger, longitudinal studies are needed to confirm these initial findings.

Adult↗

PubMed2006

Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity.

Teas represent a large family of plants containing high amounts of polyphenols that may confer health benefits in various diseases. Recently, it has been hypothesized that tea consumption may also reduce the risk of age-related neurodegenerative pathologies. Considering the deleterious role of beta-amyloid (Abeta) in the aetiology of Alzheimer's disease (AD), we investigated green and black tea extracts and flavan-3-ols (present as monomers and dimers in green and black forms, respectively) against toxicity induced by Abeta-derived peptides using primary cultures of rat hippocampal cells as model. Both green and black tea extracts (5-25 microg/mL) displayed neuroprotective action against Abeta toxicity. These effects were shared by gallic acid (1-20 microm), epicatechin gallate (ECG; 1-20 microM) and epigallocatechin gallate (EGCG; 1-10 microM), the former being the most potent flavan-3-ol. In contrast, epicatechin and epigallocatechin were ineffective in the same range of concentrations. Moreover, only tea flavan-3-ol gallate esters (i.e. ECG, EGCG) and gallic acid inhibited apoptotic events induced by Abeta(25-35). Interestingly, EGCG and gallic acid inhibited Abeta aggregation and/or the formation of Abeta-derived diffusible neurotoxin ligands. Taken together, these results indicate that the catechin gallates (through the galloyl moiety) contribute to the neuroprotective effects of both green and black teas. Moreover, the protective effect of EGCG is likely to be associated, at least in part, with its inhibitory action on Abeta fibrils/oligomers formation. These data also support the hypothesis that not only green but also black teas may reduce age-related neurodegenerative diseases, such as AD.

Amyloid beta-Peptides↗

PubMed2005

Beta-amyloid and oxidative stress jointly induce neuronal death, amyloid deposits, gliosis, and memory impairment in the rat brain.

Infusion of Fe2+, Abeta42, and buthionine-sulfoximine (FAB), but not Abeta42 alone or in combination with Fe2+, into the left cerebral ventricle of Long-Evans rats for 4 weeks induced memory impairment that was accompanied by increased hyperphosphorylated Tau protein levels in the CSF. FAB-infused animals displayed thioflavin-S-positive amyloid deposits, hyperphosphorylated Tau protein, neuronal loss, and gliosis. Animals treated with Abeta42, Fe2+, or buthionine-sulfoximine alone or in combination failed to show the histological modifications seen with FAB. This data suggests that Abeta42 is not sufficient to induce an Alzheimer's disease-like symptomatology, and it supports a model whereby a decrease in the brain's antioxidant defense system leads to the Abeta42-independent oxidative stress necessary for the peptide to induce histopathological changes and memory loss.

Amyloid↗

PubMed2005

Haploinsufficiency of cytochrome P450 17alpha-hydroxylase/17,20 lyase (CYP17) causes infertility in male mice.

Cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) is critical in determining cortisol and sex steroid biosynthesis. To investigate how CYP17 functions in vivo, we generated mice with a targeted deletion of CYP17. Although in chimeric mice Leydig cell CYP17 mRNA and intratesticular and circulating testosterone levels were dramatically reduced (80%), the remaining testosterone was sufficient to support spermatogenesis as evidenced by the generation of phenotypical black C57BL/6 mice. However, male chimeras consistently failed to generate heterozygous CYP17 mice and after five matings chimeric mice stopped mating indicating a change in sexual behavior. These results suggested that CYP17 deletion caused a primary phenotype (infertility), probably not due to the anticipated androgen imbalance and a secondary phenotype (change in sexual behavior) due to the androgen imbalance. Surprisingly, CYP17 mRNA was found in mature sperm, and serial analysis of gene expression identified CYP17 mRNA in other testicular germ cells. CYP17 mRNA levels were directly related to percent chimerism. Moreover, more than 50% of the sperm from high-percentage chimeric mice were morphologically abnormal, and half of them failed the swim test. Furthermore, 60% of swimming abnormal sperm was devoid of CYP17. These results suggest that CYP17, in addition to its role in steroidogenesis and androgen formation, is present in germ cells where it is essential for sperm function, and deletion of one allele prevents genetic transmission of mutant and wild-type alleles causing infertility followed by change in sexual behavior due to androgen imbalance.

Alleles↗

PubMed2005

Use of a device that applies external kneading-like force on the abdomen for treatment of constipation.

AIM: To evaluate the efficacy of a recently developed device that applies kneading-like motion on the abdomen in improving constipation in elderly long-term care patients. METHODS: Thirty constipated elderly patients were randomly selected from two nursing homes. They were instructed to use the device once daily for 20 min. Rate of bowel movements, volume and consistency of stool and the use of laxantia were all recorded during a 3-wk baseline period and for 12-wk treatment period. Colonic transit time (CTT) was measured in 13 patients by radiopaque markers during the baseline and at the end of treatment. RESULTS: Bowel movement rate (BM/week) increased from 1.4+/-0.4 BM/wk during baseline to 3.9+/-0.8 BM/wk during treatment (P<5.0x10(-7)). Stool amount that was "low" in 30 patients during baseline increased in 21 patients at the end of the study period (chi2 = 19.048-P = 1.3x10(-5)). Stool consistency, that was "hard" in 25 patients and "soft" in 5 patients during baseline, ameliorated in 23 patients at the end of the study (only 2 patients referred "hard" stool) (chi2 = 21.043-P = 4.0x10(-6)). The mean baseline CTT measured was 92.3+/-32.3 h at baseline and decreased to 49.4+/-31.3 h during the study period (P = 0.000208). No side effects were observed during the study period. CONCLUSION: External mechanical vibration of the abdomen reduced CTT and helped to relieve severe constipation in elderly constipated patients.

Abdomen↗