Neuroprotective Effect of Ilex Paraguariensis Intake on Brain Myelin of Lung Adenocarcinoma-Bearing Male Balb/c Mice.

Ilex paraguariensis (IP) is widely consumed as tea with high nutritional value. This plant contains several bioactive phenolic compounds, which are antioxidant and anti-inflammatory. On the other hand, lung adenocarcinoma (LAC) deleteriously involves neoplastic progression, inflammatory paraneoplastic syndromes, and death. Given that brain is a frequent target of this illness, our objective was to determine the neuroprotective effect of IP consumption in LAC-bearing mice. They were orally treated with 50 mg of IP extract/kg/day (IP50) for 3 weeks. Results (phenolic compounds, lipid peroxides, interleukin 6-IL-6-, tumor necrosis factor alpha -TNFα-, and luxol-stained myelination) were compared with respect to untreated controls (C) by the T test. IP50 significantly lowed brain IL-6 (2858.12 ± 57.81 pg g-1 vs. 3801.30 ± 27.34 pg g-1), whereas other variables differed in a less extent. C brains showed demyelination (low luxol-staining contrast between gray and white matters), with IP50 increasing myelination (P < 0.05). In conclusion, LAC deleterious effects on murine brain were prevented by dietary IP, which is an original discovery to develop a nutritional approach against cancer neurological compromise.

Effects of bioavailable phenolic compounds from Ilex paraguariensis on the brain of mice with lung adenocarcinoma.

Lung carcinoma is one of the most common cancers and has a high mortality. Recently, we showed that it produces neurological paraneoplastic syndrome, with Ilex paraguariensis (IP) extract exerting palliative effects due to its content of phenolic compounds. It is possible, therefore, that these diet agents can arrive at the brain and exert neuroprotection, after the oral intake of IP. Here, the aim was to investigate the protective role of bioavailable IP compounds on the telencephalon and diencephalon in lung adenocarcinoma-bearing BALB/cJ males. Mice aged 2 months were treated for 3 weeks with 0-100 IP mg·kg-1 ·day-1 . HPLC-UV revealed the presence of chlorogenic acid and quercetin in brain regions, liver, and tumour, in an IP dose-dependent manner. Brain was also evaluated histologically, and interleukin-6 was measured by ELISA. Chlorogenic acid was the major compound found in brain, whereas quercetin was observed at the diencephalon to a lesser extent. Both compounds were involved in IP dose-dependent diencephalic interleukin-6 reduction. Histology suggested cellular protection with less apoptosis in chlorogenic-exposed areas. Taken together, chlorogenic acid and quercetin from dietary IP were bioavailable and bioactive in brain, thereby attenuating lung cancer-related neuroinflammation and damage. These findings support plant-based strategies to improve prognosis.

[Modifications of the superoxide anion level in breast milk by the intake of flavonoids and carotenoids]. / Modificaciones en el nivel de anión superóxido en leche materna, según la ingesta de flavonoides y carotenoides.

OBJECTIVE: To associate the intake of flavonoids and carotenoids with the breast milk level of superoxide anion, as an oxidative stress marker. MATERIALS AND METHODS: 100 women from Cordoba (Argentina), who breastfed within the first postpartum 6 months, were studied during the 2013-2015 period, by evaluating their sanitary data, food intake and anion level in milk with multiple logistic regression. RESULTS: The intake of flavonoids, provitamin A carotenoids and non-provitamin carotenoids was 72 (61) mg/d, 1813 (1 657) µg/d y 5427 (3 664) µg/d, respectively. The anion was associated with the intake of flavanols (OR=1.081; CI95 1.001-1.167) y flavanones (OR=1.025; CI95 1.001-1.048). This effect was not seen with other flavonoids and carotenoids. CONCLUSIONS: Intake of flavanols and flavanones increases milk oxidation risk, which is relevant to develop diet recommendations.

OBJETIVO: Asociar la ingesta de flavonoides y carotenoides con el nivel en leche materna del anión superóxido, como marcador de estrés oxidativo. MATERIAL Y MÉTODOS: Durante el periodo 2013-2015 se estudió a 100 mujeres lactantes de Córdoba (Argentina), dentro los primeros seis meses posparto; se evaluaron sus datos sanitarios, ingesta alimentaria y nivel lácteo del anión con regresión logística múltiple. RESULTADOS: La ingesta de flavonoides, carotenoides provitamínicos y carotenoides no provitaminas fue de 72 (61) mg/día, 1 813 (1657) µg/día y 5 427 (3664) µg/día, respectivamente. El anión se asoció con la ingesta de flavanoles (RM=1.081; IC95 1.001-1.167) y flavanonas (RM=1.025; IC95 1.001-1.048). No se observó este efecto con otros flavonoides ni con los carotenoides. CONCLUSIONES: La ingesta de flavanoles y flavanonas aumenta el riesgo de oxidación láctea, lo cual es relevante para realizar recomendaciones dietéticas.

Selective CB2 receptor agonists. Part 1: the identification of novel ligands through computer-aided drug design (CADD) approaches.

Computer-aided drug design scaffold hopping strategies were utilized to identify new classes of CB2 agonists when compounds of an established series with low nanomolar potency were challenging to optimize for good drug-like properties. Use of ligand-based design strategies through BI Builder (a tool for de novo design) and PharmShape (a virtual screening software package) approaches led to the discovery of new chemotypes. Specifically, compounds containing azetidine-, proline-, and piperidine-based cores were found to have low nanomolar and picomolar CB2 agonist activities with drug-like properties considered appropriate for early profiling.

Selective CB2 receptor agonists. Part 2: Structure-activity relationship studies and optimization of proline-based compounds.

Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia.

Selective CB2 receptor agonists. Part 3: the optimization of a piperidine-based series that demonstrated efficacy in an in vivo neuropathic pain model.

A novel class of potent cannabinoid receptor 2 (CB2) agonists based on a (S)-piperidine scaffold was identified using ligand-based pharmacophore models. Optimization of solubility and metabolic stability led to the identification of several potent CB2 agonists (e.g., 30) that displayed selectivity over cannabinoid receptor 1 (CB1) and acceptable drug like properties. In rats, compound 30 demonstrated a favorable pharmacokinetic profile and efficacy in a Streptozotocin-induced diabetic neuropathy model, with full reversal of mechanical hyperalgesia.

Amplicon-Based Bisulfite Conversion-NGS DNA Methylation Analysis Protocol.

DNA methylation is an important epigenetic modification that regulates chromatin structure and the cell-type-specific expression of genes. The association of aberrant DNA methylation with many diseases, as well as the increasing interest in modifying the methylation mark in a directed manner at genomic sites using epigenome editing for research and therapeutic purposes, increases the need for easy and efficient DNA methylation analysis methods. The standard approach to analyze DNA methylation with a single-cytosine resolution is bisulfite conversion of DNA followed by next-generation sequencing (NGS). In this chapter, we describe a robust, powerful, and cost-efficient protocol for the amplification of target regions from bisulfite-converted DNA, followed by a second PCR step to generate libraries for Illumina NGS. In the two consecutive PCR steps, first, barcodes are added to individual amplicons, and in the second PCR, indices and Illumina adapters are added to the samples. Finally, we describe a detailed bioinformatics approach to extract DNA methylation levels of the target regions from the sequencing data. Combining barcodes with indices enables a high level of multiplexing allowing to sequence multiple pooled samples in the same sequencing run. Therefore, this method is a robust, accurate, quantitative, and cheap approach for the readout of DNA methylation patterns at defined genomic regions.

Locus-Specific and Stable DNA Demethylation at the H19/IGF2 ICR1 by Epigenome Editing Using a dCas9-SunTag System and the Catalytic Domain of TET1.

DNA methylation is critically involved in the regulation of chromatin states and cell-type-specific gene expression. The exclusive expression of imprinted genes from either the maternal or the paternal allele is regulated by allele-specific DNA methylation at imprinting control regions (ICRs). Aberrant DNA hyper- or hypomethylation at the ICR1 of the H19/IGF2 imprinting locus is characteristic for the imprinting disorders Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS), respectively. In this paper, we performed epigenome editing to induce targeted DNA demethylation at ICR1 in HEK293 cells using dCas9-SunTag and the catalytic domain of TET1. 5-methylcytosine (5mC) levels at the target locus were reduced up to 90% and, 27 days after transient transfection, >60% demethylation was still observed. Consistent with the stable demethylation of CTCF-binding sites within the ICR1, the occupancy of the DNA methylation-sensitive insulator CTCF protein increased by >2-fold throughout the 27 days. Additionally, the H19 expression was increased by 2-fold stably, while IGF2 was repressed though only transiently. Our data illustrate the ability of epigenome editing to implement long-term changes in DNA methylation at imprinting control regions after a single transient treatment, potentially paving the way for therapeutic epigenome editing approaches in the treatment of imprinting disorders.

Aortic dissection detection and thrombus structure quantification using volumetric ultrasound, histology, and scanning electron microscopy.

Aortic dissection occurs when a weakened portion of the intima tears, and a separation of layers propagates along the aortic wall to form a false lumen filled with active blood flow or intramural thrombus. The unpredictable nature of aortic dissection formation and need for immediate intervention leaves limited serial human image data to study the formation and morphological changes that follow dissection. We used volumetric ultrasound examination, histology, and scanning electron microscopy (SEM) to examine intramural thrombi at well-defined timepoints after dissection occurs in apolipoprotein E-deficient mice infused with angiotensin II (n = 71). Stratification of red blood cell (RBC) morphologies (biconcave, intermediate biconcave, intermediate polyhedrocyte, and polyhedrocyte) in the thrombi with scanning electron microscopy (n = 5) was used to determine degree of thrombus deposition/contraction. Very few biconcave RBCs (1.2 ± 0.6%) were in the thrombi, and greater amounts of intermediate biconcave RBCs (25.8 ± 6.7%) were located in the descending thoracic portion of the dissection while more polyhedrocytes (14.6 ± 5.1%) and fibrin (42.3 ± 4.5%; P < .05) were found in the distal suprarenal aorta. Thrombus deposition likely plays some role in patient outcomes, and this multimodality technique can help investigate thrombus deposition and characteristics in experimental animal models and human tissue samples.

Assessment of dietary intakes and feeding practices in children aged 6-23 months in a town in the Northeast region of Argentina. / Evaluación de las ingestas dietéticas y prácticas alimentarias en niños de 6 a 23 meses en una localidad del noreste argentino.

INTRODUCTION: An adequate quantity and quality of complementary feeding is essential during the first 2 years of life. The objective of this study was to assess dietary intakes and feeding practices in children aged 6-23 months in a town in the Northeast region of Argentina. POPULATION AND METHODS: Descriptive, crosssectional study (second semester of 2019). Intakes from 24-hour dietary recall interviews conducted among caregivers of children aged 6-23 months were assessed. Data were compared to dietary reference intakes. Feeding practices were assessed as per the World Health Organization's indicators. RESULTS: A total of 138 children aged 6-23 months were assessed. The mean adequacy ratio of energy and vitamins A, D, and E was below 100% for all ages, whereas the protein adequacy for children aged 7-12 and 13-23 months was 142.8% and 168.1%, respectively. A remarkable number of cases had energy and vitamin A intakes below the estimated average requirement. In relation to feeding practice indicators, 50.8% of infants received a minimum acceptable diet. CONCLUSIONS: There is a high prevalence of an inadequate level of energy and critical nutrient intake during complementary feeding of the children aged 6-23 months included in the study. Nutritional interventions that promote feeding practices to improve micronutrient intake would be highly important for children's current and future health.

Introducción. Una alimentación complementaria adecuada en cantidad y calidad resulta esencial durante los primeros dos años de vida. El objetivo del estudio fue evaluar la ingesta de nutrientes y prácticas alimentarias en niños de 6 a 23 meses de una localidad del noreste argentino. Población y métodos. Estudio descriptivo transversal (segundo semestre del 2019). Se evaluaron las ingestas de 24 horas mediante recordatorios a los cuidadores de niños de 6 a 23 meses. Los datos se compararon con las ingestas dietéticas de referencia. Las prácticas alimentarias se evaluaron según los indicadores establecidos por la Organización Mundial de la Salud. Resultados. Se evaluaron 138 niños de 6 a 23 meses de edad. La energía y las vitaminas A, D y E presentaron porcentajes medios de adecuación inferiores al 100 % en todas las edades, mientras que las proteínas alcanzaron una adecuación promedio del 142,8 % y el 168,1 % para los niños de 7-12 meses y de 13-23 meses, respectivamente. Los nutrientes que presentaron una proporción considerable de casos con ingestas por debajo del requerimiento promedio estimado en todos los grupos fueron la energía y la vitamina A. En cuanto a los indicadores de prácticas alimentarias, 50,8 % de los lactantes recibió una dieta mínima aceptable. Conclusiones. Existe una alta prevalencia de inadecuación energética y de nutrientes críticos durante la alimentación complementaria en los niños de 6 a 23 meses incluidos en el estudio. Intervenciones nutricionales que promuevan prácticas alimentarias que mejoren la ingesta de micronutrientes serían de suma importancia para su salud actual y futura.

Deletion of bone marrow-derived receptor for advanced glycation end products inhibits atherosclerotic plaque progression.

BACKGROUND: The multiligand receptor for advanced glycation end products (RAGE) of the immunoglobulin superfamily is expressed on multiple cell types implicated in the inflammatory response in atherosclerosis. We sought to determine the role of bone marrow-derived RAGE in different stages of atherosclerotic development in apolipoprotein E-deficient mice (apoE(-/-)). METHODS: Seven- and 23-week-old apoE(-/-) mice (n = 40) were lethally irradiated and given bone marrow from RAGE null (RAGE(-/-)/apoE(-/-)) or RAGE-bearing (RAGE(+/+)/apoE(-/-)) mice to apoE(-/-) mice to generate double knockout bone marrow chimera (RAGE(-/-)/apoE(-/-bmc) and RAGE(+/+)/apoE(-/-bmc)-, respectively). After 16 weeks on a standard chow diet, mice were sacrificed and atherosclerotic lesion formation was evaluated. RESULTS: Plaques in the aortic root of the young mice showed no significant difference in maximum plaque size (217,470 ± 17,480 µm(2) for the RAGE(-/-) /apoE(-/-bmc) mice compared to 244,764 ± 45,840 µm(2)), whereas lesions in the brachiocephalic arteries of the older RAGE(-/-)/apoE(-/-bmc) mice had significantly smaller lesions (94,049 ± 13,0844 µm(2) vs. 145,570 ± 11,488 µm(2), P < 0.05) as well as reduced average necrotic core area (48,600 ± 9220 µm(2) compared to 89,502 ± 10,032 µm(2), P < 0.05) when compared to RAGE(+/+)/apoE(-/-bmc) mice. Reduced plaque size and more stable plaque morphology was associated with significant reduced expression of VCAM-1, ICAM-1 and MCP-1. Accumulation of the RAGE ligand HMGB-1 was also significantly reduced within the lesions of RAGE(-/-)/apoE(-/-bmc) mice. CONCLUSIONS: This study demonstrates that bone marrow-derived RAGE is an important factor in the progression of atherosclerotic plaques.

Nicotinic acid has anti-atherogenic and anti-inflammatory properties on advanced atherosclerotic lesions independent of its lipid-modifying capabilities.

Inflammation contributes to atherosclerotic plaque initiation and progression. Recent studies suggest that nicotinic acid has anti-inflammatory effects independent of its lipid-modifying capabilities. We assessed the hypothesis that administration of nicotinic acid to older apolipoprotein E (apoE)-deficient mice with established lesions will reduce lesion size and plaque inflammation independent of its lipid-modifying effects. Therefore nicotinic acid was administered to 27-week-old apo E-deficient mice exhibiting advanced atherosclerotic lesions within the innominate artery. After 27 weeks of treatment both animal groups had no significant changes in plasma lipid levels. Mice treated with nicotinic acid (n = 22) demonstrated a 30% reduction in total lesion area compared with controls (n = 20). Furthermore, they revealed a more stable plaque composition with an increase in fibrous cap thickness and a reduction in the size of the necrotic core. Immunohistochemistry demonstrated a reduced accumulation of macrophages and a reduced expression of vascular cell adhesion molecule-1 and tissue factor. Additionally, administration of nicotinic acid significantly reduced tumor necrosis factor alpha expression in the thoracic aorta as demonstrated by real-time PCR. In conclusion, these data suggest that long-term administration of nicotinic acid has anti-atherogenic and anti-inflammatory properties on advanced atherosclerotic lesions, which are independent of its lipid-modifying actions.

Aryl 1,4-diazepane compounds as potent and selective CB2 agonists: optimization of drug-like properties and target independent parameters.

A high throughput screening campaign identified aryl 1,4-diazepane compounds as potent and selective cannabinoid receptor 2 agonists as compared to cannabinoid receptor 1. This class of compounds suffered from poor drug-like parameters as well as low microsomal stability and poor solubility. Structure-activity relationships are described with a focus on improving the drug-like parameters resulting in compounds with improved solubility and permeability.

1,4-Diazepane compounds as potent and selective CB2 agonists: optimization of metabolic stability.

A high-throughput screening campaign has identified 1,4-diazepane compounds which are potent Cannabinoid receptor 2 agonists with excellent selectivity against the Cannabinoid receptor 1. This class of compounds suffered from low metabolic stability. Following various strategies, compounds with a good stability in liver microsomes and rat PK profile have been identified.

Chemiluminescence determination of antioxidant property of Zizyphus mistol and Prosopis alba during oxidative stress generated in blood by Hemolytic Uremic Syndrome-producing Escherichia coli.

This study was undertaken to elucidate the antioxidant effect of Zizyphus mistol and Prosopis alba, with the hypothesis that these fruits can counteract the induction of reactive oxygen species (ROS) caused by toxins produced by Escherichia coli. In the search of nutrients effective against the Hemolytic Uremic Syndrome (HUS), we detected by chemiluminescence a protective role of both plants, due to their natural antioxidants significantly decreasing the levels of ROS induced by toxins from E. coli in blood. The ferric reducing antioxidant power (FRAP) was found to be higher in Z. mistol than in P. alba. The chemical analyses of the phenols and flavonoids present in the fruit extracts indicated that the FRAP correlated with the amount of phenolic compounds, but not with the flavonoids analyzed. Both fruits studied reduce the induction of ROS, and in this way help to prevent the development of complications related to oxidative stress generated in the blood of patients with HUS.

Beneficial effect of Berberis buxifolia Lam, Ziziphus mistol Griseb and Prosopis alba extracts on oxidative stress induced by chloramphenicol.

The chemiluminescence of luminol, a measure of oxidative stress, increased immediately as a consequence of reactive oxygen species (ROS) stimulated by this antibiotic. The effect of Ch was dose dependent with maximum stimulus at 8 mg/ml (Vmax); above this concentration the cells began to reduce the production of ROS. The oxidative injury of Ch was counteracted by water extracts of Berberis buxifolia lam, Zizyphus mistol Griseb and Prosopis alba, indigenous fruits from Argentina. The relatively light units (RLU) emitted decreased immediately as a consequence of a protective effect exerted by the extracts of these fruit extracts on blood cells. The three indigenous fruit extracts reduced to a different extent the oxidative injury caused by Ch. B.buxifolia lam exhibited the highest antioxidant capacity followed by Z.mistol Griseb. Water extracts of both fruit extracts were the most effective against the oxidative stress, while P.alba presented better antioxidant capacity in the ethanolic fraction obtained. Hexane extracts showed low protective action on blood cells, with little reduction of area under curve (AUC) of RLU plotted versus time. Leukocytes remained viable in blood samples incubated for 3h with Ch and water extracts of B. buxifolia lam or Z. mistol Griseb (97.1% and 92.5% viability by Trypan blue exclusion, respectively); whereas with Ch only the cells were stressed and viability decreased to 30%. The three fruit extracts protected the viability of leukocytes in parallel with the decrease of ROS. Erythrocytes were not lysed in the presence of Ch.

Pharmacological Activity of Quercetin and 5 Caffeoylquinic Acid Oral Intake in Male Balb/c Mice with Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LAC) is a major worldwide cause of death by cancer, it shows high aggressiveness, functional decline, systemic compromise and severe cachexia, which might be counteracted by dietary redox-active phytochemicals. Therefore, our aim was to establish the anticancer effects of the oral intake of quercetin and 5 caffeoylquinic acid. METHODS: LAC-1-bearing male Balb/c mice received quercetin (0-25 µg/kg/d) and 5 caffeoylquinic acid (0-120 µg/kg/d) for three weeks, with different organic and biochemical variables being then compared with ANOVA and the Fisher Test (p <0.05). RESULTS: Quercetin delayed 1.18 fold tumour appearance and increased 8.87 fold non-neoplastic body weight gain, whereas 5 caffeoylquinic acid did it in a lesser extent (1.17 and 2.48 fold, respectively), with tumour weight being consequent with the evolution time. Quercetin induced >1.15 fold tumour hydroperoxides and lipoperoxides, whereas 5 caffeoylquinic acid induced only lipoperoxides. Although both phytochemicals reduced <0.85 fold hydroperoxides and lipoperoxides in the kidney, only quercetin was also antioxidant in the liver. Additionally, 5 caffeoylquinic acid increased >1.15 fold hepatic and renal weights. Although these phytochemicals did not modify telencephalic interleukin 6 production, quercetin augmented 2.51 fold interleukin 6 in the diencephalon, whereas 5 caffeoylquinic acid decreased it 0.43 fold. CONCLUSIONS: Quercetin delayed lung adenocarcinoma appearance and increased the non-neoplastic body weight gain in mice with tumour oxidative stress, without brain interleukin 6 participation. 5 caffeoylquinic acid showed similar effects, although they were weaker. Additionally, quercetin acted as a hepatic and renal antioxidant, whereas 5 caffeoylquinic acid only exerted this effect in the kidney. Therefore, safe oral doses of this flavonoid are promissory to modulate lung cancer progression, with further studies being encouraged.

Cross-linking of protein crystals as an aid in the generation of binary protein-ligand crystal complexes, exemplified by the human PDE10a-papaverine structure.

Protein crystallography has proven to be an effective method of obtaining high-resolution structures of protein-ligand complexes. However, in certain cases only apoprotein structures are readily available and the generation of crystal complexes is more problematic. Some crystallographic systems are not amenable to soaking of ligands owing to crystal-packing effects and many protein-ligand complexes do not crystallize under the same conditions as used for the apoprotein. Using crystals of human phosphodiesterase 10a (hPDE10a) as an example of such a challenging crystallographic system, the structure of the complex with papaverine was obtained to 2.8 A resolution using protein crystals cross-linked by glutaraldehyde prior to soaking of the ligand. Inspection of the electron-density maps suggested that the correct mode of binding was obtained in one of the two monomers in the asymmetric unit and inspection of crystal-packing contacts explained why cocrystallization experiments and soaking of crystals that were not cross-linked were unsuccessful.

Critical role of macrophages in glucocorticoid driven vascular calcification in a mouse-model of atherosclerosis.

OBJECTIVE: Macrophage-derived products are known to play a crucial role during atherogenesis and vascular calcification. Glucocorticoids (GC) are important modulators of immune cell functions, but their specific effects on macrophages behavior during plaque formation are not defined. The present study was therefore designed to investigate the effects of macrophage-specific deletion of the glucocorticoid receptor (GR(LysMCre)) on atherogenesis and vascular calcification in a hyperlipidemic mouse-model. METHODS AND RESULTS: Bone marrow was isolated from GR(LysMCre) mice and wild-type controls (GR(flox)) and subsequently transplanted into lethally irradiated LDL-receptor-deficient mice. Animals were fed a Western-type diet for 15 or 24 weeks, and atherosclerotic lesions within the aortic sinus were evaluated. At both time points, no significant difference in serum lipid and corticosterone concentrations, atherosclerotic lesion size and macrophage-content within the lesions could be observed. However, GR(LysMCre) mice showed less calcification as well as a significant reduction of RANKL, BMP2, and Msx2 expression within the vasculature. In vitro studies using conditioned media from macrophages which had been stimulated with dexamethasone demonstrated a dose-dependent increase in calcium deposition by vascular smooth muscle cells. CONCLUSIONS: This study demonstrates that macrophage-specific glucocorticoid receptor inactivation reduces vascular calcification without affecting atherosclerotic lesion size in LDL receptor-deficient mice.

[Effectiveness of inpatient psychodynamic psychotherapy: a follow-up study]. / Langzeit-Katamnese zur Effektivität einer stationären psychodynamischen Psychotherapie.

OBJECTIVES: This study investigates the stability of symptomatic and interpersonal changes after inpatient psychodynamic psychotherapy. METHODS: 437 patients were assessed 3 to 5 years after discharge with the Symptom Checklist (SCL-90-R), the Inventory of Interpersonal Problems (IIP), global assessment of effectiveness and utilization of posttreatment psychotherapy. The therapist's perspective was evaluated by the Impairment Severity Score (BSS), the Global Assessment of Functioning Scale (GAF), and the Clinical Global Impressions (CGI). RESULTS: Patients improved in all SCL-90-R scales significantly. The Global Severity Index (GSI) effect size was 0.81 posttreatment and 0.82 at follow-up. All IIP scales improved significantly; effect size of IIP total score was 0.40 at posttreatment and 0.60 at follow-up. There were substantial gains in BSS,GAF, and CGI. 84% of the patients were in psychotherapy after dismissal. DISCUSSION: Posttreatment results were in accordance with comparable studies. The results are stable on a symptomatic level and improve further on an interpersonal level.