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1.
Heliyon ; 10(8): e29464, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38638950

ABSTRACT

The temporary closure of the Outpatient Psychotherapy Clinic at the Sigmund Freud Private University in Vienna during the Covid-19 pandemic demanded an immediate and unexpected reaction to assure further psychotherapeutic services. Both psychotherapists and patients were forced into a rapid transition to online psychotherapy. While Covid-19 research has comprehensively described challenges of online psychotherapies, we were interested in learning specifically how early stage psychotherapists-in-training, who started their clinical work with patients exclusively in the online setting, experienced this unprecedented clinical situation. Sixteen in-depth interviews were conducted with psychotherapists in training. The data were analyzed using a thematic analysis. The analysis revealed how psychotherapists in training were able to cultivate a set of early-training resources and competencies in the online therapy setting without evidence-based guidelines from supervisors and the institution. This study highlighted the necessity of incorporating specific and novel educational input that is necessary for achieving specific online skills in the early training phase. Recognizing that the therapeutic landscape has undergone an irreversible transformation, the data suggest that distinct techniques are necessary to equip early-training psychotherapists for the now commonly practiced alternation between online setting and in-person setting in psychotherapeutic processes.

2.
Front Psychol ; 14: 1118659, 2023.
Article in English | MEDLINE | ID: mdl-37416537

ABSTRACT

Introduction: The present study provides longitudinal data on the development of receptive and expressive grammar in children and adolescents with Down syndrome and addresses the role of nonverbal cognitive abilities and verbal short-term memory for morphosyntactic development. Method: Seventeen German-speaking individuals with Down syndrome (aged 4;6-17;1 years at first testing (T1)) were assessed twice, 4;4-6;6 years apart. For a subset of five participants, there was also a third assessment 2 years after the second. Receptive grammar, nonverbal cognition, and verbal short-term memory were tested using standardized measures. For expressive grammar, elicitation tasks were used to assess the production of subject-verb agreement and of wh-questions. Results: At group level, the participants showed a significant increase in grammar comprehension from T1 to T2. However, progress diminished with increasing chronological age. Notable growth could not be observed beyond the age of 10 years.With respect to expressive grammatical abilities, progress was limited to those participants who had mastered verbal agreement inflection around age 10 years. Individuals who did not master verbal agreement by late childhood achieved no progress in producing wh-questions, either.There was an increase in nonverbal cognitive abilities in the majority of participants. Results for verbal short-term memory followed a similar pattern as those for grammar comprehension. Finally, neither nonverbal cognition nor verbal short-term memory were related to changes in receptive or expressive grammar. Discussion: The results point to a slowdown in the acquisition of receptive grammar which starts before the teenage years. For expressive grammar, improvement in wh-question production only occurred in individuals with good performance in subject-verb agreement marking, which suggests that the latter might have a trigger function for further grammatical development in German-speaking individuals with Down syndrome. The study provides no indication that nonverbal cognitive abilities or verbal short-term memory performance determined the receptive or expressive development. The results lead to clinical implications for language therapy.

3.
Acta Ophthalmol ; 98(4): e407-e415, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31736269

ABSTRACT

PURPOSE: To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes. METHODS: In a prospective, randomized, controlled, double-blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm-Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20. RESULTS: The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM-1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM-1) (weeks 2 and 8) and monocyte chemo-attractant protein 1 (MCP-1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time-points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 µm) compared with baseline (440 ± 144 µm) in the Lucentis group. CONCLUSION: The dexamethasone implant affected the aqueous cytokines and proteins MCP-1, sICAM-1, sVCAM-1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections.


Subject(s)
Aqueous Humor/metabolism , Cytokines/metabolism , Dexamethasone/administration & dosage , Diabetic Retinopathy/drug therapy , Macular Edema/drug therapy , Ranibizumab/administration & dosage , Visual Acuity , Aged , Angiogenesis Inhibitors/administration & dosage , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Dose-Response Relationship, Drug , Double-Blind Method , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Intravitreal Injections , Macula Lutea/pathology , Macular Edema/diagnosis , Macular Edema/etiology , Male , Middle Aged , Prospective Studies , Tomography, Optical Coherence/methods , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors
4.
Prax Kinderpsychol Kinderpsychiatr ; 68(6): 540-554, 2019 Sep.
Article in German | MEDLINE | ID: mdl-31480949

ABSTRACT

German Military Families: A Qualitative Inquiry of Strategies of Coping with the Fathers' Absence Military families with experiences of deployment are subject to multiple stressors. In this research an explorative qualitative design was used to identify specific challenges, resources and strategies of coping within the families, focusing on the children's perspective. Results show that the fathers' absence causes vital changes in the family system, which demand specific strategies to deal with the abrupt emotional and social challenges. Four of these coping strategies will be presented in this article. Furthermore, resources embedded in the social environment as well as supportive structures provided by the German military will be discussed. Two hypotheses were formulated to outline the findings that the preparation for a deployment as well as patterns of communication about the father's absence are the most crucial factors for the children's resilience in the case of military families.


Subject(s)
Adaptation, Psychological , Fathers , Military Family/psychology , Child , Emotions , Humans , Male , Qualitative Research
5.
World J Clin Oncol ; 10(3): 136-148, 2019 Mar 24.
Article in English | MEDLINE | ID: mdl-30949443

ABSTRACT

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases (RTKs) and members of the fibroblast growth factor receptors (FGFR)-family. Single-nucleotide polymorphism (SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC. AIM: To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted. METHODS: Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany. Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP. Patients' clinical data with a minimum follow-up of 5 years were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis. RESULTS: Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high" (+++) in 74 (26%), "intermediate" (++) in 103 (36.3%), and "low" (+) in 107 (36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors (33.8%), 84 of them (29.6%) having a heterozygous and 12 (4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage (P < 0.004), local metastasis (P < 0.0001) and reduced disease-free survival (P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival (P < 0.003). CONCLUSION: In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention.

6.
Clin Linguist Phon ; 32(3): 267-284, 2018.
Article in English | MEDLINE | ID: mdl-28846461

ABSTRACT

The aim of the study is to investigate if German children with hearing loss (HL) display persisting problems in comprehending complex sentences and to find out whether these problems can be linked to limitations in phonological short-term memory (PSTM). A who-question comprehension test (picture pointing) and a nonword repetition (NWR) task were conducted with 21 German children with bilateral sensorineural HL (ages 3-4) and with age-matched 19 normal hearing (NH) children. Follow-up data (ages 6-8) are reported for 10 of the children with HL. The data reveal that the comprehension of who-questions as well as PSTM was significantly more impaired in children with HL than in children with NH. For both groups of participants, there were no correlations between question comprehension scores and performance in the NWR test. Syntactic complexity (subject vs. object question) affected question comprehension in children with HL, however, these problems were overcome at school age. In conclusion, the data indicate that a hearing loss affects the comprehension of complex sentences. The observed problems did, however, not persist and were, therefore, unlikely to be caused by a genuine syntactic deficit. For the tested wh-questions, there is no indication that syntactic comprehension problems of children with HL are due to limitations in PSTM.


Subject(s)
Comprehension/physiology , Hearing Loss/psychology , Memory, Short-Term/physiology , Speech Perception , Child , Child, Preschool , Female , Germany , Humans , Language Development , Linguistics , Male
7.
J Commun Disord ; 67: 35-48, 2017 May.
Article in English | MEDLINE | ID: mdl-28544920

ABSTRACT

For children with sensorineural hearing loss the ability to understand wh-questions might be particularly challenging because they often have only restricted access to spoken language input during optimal periods of language acquisition. In previous research it has been suggested that this restricted input during critical stages in language acquisition might lead to syntactic deficits that persist into adolescence. In this study we want to pursue this issue by investigating the comprehension of wh-questions in German children with bilateral sensorineural hearing loss. We report results of a who-question comprehension task in a group of 21 3- to 4-year-old German hard-of-hearing children compared to a group of age-matched children with normal hearing. The group data and individual performance patterns suggest that the syntactic comprehension difficulties observed in some, but not all, of the children with hearing loss reflect a delay in the acquisition of who-question comprehension rather than a persistent syntactic deficit. Follow-up data elicited from a subgroup of children confirm this supposition.


Subject(s)
Comprehension/physiology , Hearing Loss, Sensorineural/psychology , Language Development , Child, Preschool , Female , Germany , Humans , Male , Persons With Hearing Impairments/psychology
8.
Logoped Phoniatr Vocol ; 41(1): 9-26, 2016.
Article in English | MEDLINE | ID: mdl-25175166

ABSTRACT

Despite modern hearing aids, children with hearing impairment often have only restricted access to spoken language input during the 'critical' years for language acquisition. Specifically, a sensorineural hearing impairment affects the perception of voiceless coronal consonants which realize verbal affixes in German. The aim of this study is to explore if German hearing-impaired children have problems in producing and/or acquiring inflectional suffixes expressed by such phonemes. The findings of two experiments (an elicitation task and a picture-naming task) conducted with a group of hearing-impaired monolingual German children (age 3-4 years) demonstrate that difficulties in perceiving specific phonemes relate to the avoidance of these same sounds in speech production independent of the grammatical function these phonemes have.


Subject(s)
Child Language , Disabled Children/psychology , Hearing Loss, Sensorineural/psychology , Persons With Hearing Impairments/psychology , Phonetics , Speech Acoustics , Speech Perception , Voice Quality , Age Factors , Case-Control Studies , Child Behavior , Child, Preschool , Female , Germany , Hearing Loss, Sensorineural/diagnosis , Humans , Male , Speech Production Measurement , Verbal Behavior , Vocabulary
9.
Clin Hemorheol Microcirc ; 62(4): 345-57, 2015 Sep 25.
Article in English | MEDLINE | ID: mdl-26444606

ABSTRACT

AIMS: The purpose of the study was to investigate, using cardiac magnetic resonance (CMR), the presence and time course of microvascular obstruction (MO) in patients with acute myocardial infarction (AMI), and to test its relationship with cardiac remodeling and clinical outcomes. METHODS AND RESULTS: 53 patients with AMI and successful percutaneous reperfusion underwent CMR examination at four separate timepoints: within the first 48 hours, at 10 days, at six and twelve months after infarction. MO was quantified immediately (early imaging) and 10 minutes (late imaging) after contrast administration in each session. The extent of MO decreased from early to late imaging at both the first and the second CMR exam (p≤0.001). Early MO was absent in 18(36%) patients both at 48 hours and 10 days after AMI. At 1 year follow-up, LVEF in these patients improved to normal (median = 62% (53-70)). Early MO was present in the first but not in the second CMR in 13 (26%) patients; LVEF at one year in these patients reached a median = 52% (47-61). Finally, Early MO was present in both exams in 19 (38%) patients, who at 1 year after infarction had a LVEF of median = 49% (42-54, P≤0.001 across groups). The time course of MO was a predictor of prognosis upon Kaplan-Meier analysis (P = 0.035). The presence of MO at 10 days after AMI was associated with a higher risk of MACE during a 5-years follow-up. CONCLUSIONS: The presence of MO within 48 hours after AMI, and its time course in the following ten days, provides complementary information on both functional myocardial recovery and long-term outcome.


Subject(s)
Contrast Media/therapeutic use , Magnetic Resonance Imaging/methods , Myocardial Infarction/diagnostic imaging , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Reperfusion
10.
Logoped Phoniatr Vocol ; 37(2): 83-93, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22432566

ABSTRACT

Many hard-of-hearing children show delays or disorders in the acquisition of morphology and syntax. There is an on-going discussion how these difficulties are connected to problems in the auditory domain. The article focuses on coronal consonants that function as suffixes in the German verbal inflectional system. Here we present a new test we developed to evaluate the ability to discriminate these consonants in syllabic offset positions. A pilot study with 22 hearing-impaired (HI) children and 15 typically developing (TD) children reveals significantly lower discrimination scores in the HI group. The results highlight the necessity to measure the capacity to distinguish particular phonemes at specific syllable positions, when considering the impact of a hearing impairment on language acquisition.


Subject(s)
Audiometry, Speech , Child Language , Hearing Loss/diagnosis , Language , Persons With Hearing Impairments/psychology , Speech Perception , Age Factors , Case-Control Studies , Child, Preschool , Discrimination, Psychological , Female , Germany , Hearing Loss/psychology , Humans , Intelligence Tests , Male , Pilot Projects , Predictive Value of Tests , Psychoacoustics , Severity of Illness Index , Speech Acoustics , Speech Intelligibility , Video Recording
11.
PLoS One ; 6(12): e25096, 2011.
Article in English | MEDLINE | ID: mdl-22162746

ABSTRACT

Current treatments for HBV chronic carriers using interferon alpha or nucleoside analogues are not effective in all patients and may induce the emergence of HBV resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine family, inhibits HBV replication by destabilizing capsid assembly. The aim of this study was to determine the antiviral effect of Bay 41-4109 in a mouse model with humanized liver and the spread of active HBV. Antiviral assays of Bay 41-4109 on HepG2.2.15 cells constitutively expressing HBV, displayed an IC(50) of about 202 nM with no cell toxicity. Alb-uPA/SCID mice were transplanted with human hepatocytes and infected with HBV. Ten days post-infection, the mice were treated with Bay 41-4109 for five days. During the 30 days of follow-up, the HBV load was evaluated by quantitative PCR. At the end of treatment, decreased HBV viremia of about 1 log(10) copies/ml was observed. By contrast, increased HBV viremia of about 0.5 log(10) copies/ml was measured in the control group. Five days after the end of treatment, a rebound of HBV viremia occurred in the treated group. Furthermore, 15 days after treatment discontinuation, a similar expression of the viral capsid was evidenced in liver biopsies. Our findings demonstrate that Bay 41-4109 displayed antiviral properties against HBV in humanized Alb-uPA/SCID mice and confirm the usefulness of Alb-uPA/SCID mice for the evaluation of pharmaceutical compounds. The administration of Bay 41-4109 may constitute a new strategy for the treatment of patients in escape from standard antiviral therapy.


Subject(s)
Albumins/metabolism , Antiviral Agents/pharmacology , Hepatitis B virus/metabolism , Hepatitis B/drug therapy , Pyridines/pharmacology , Pyrimidines/pharmacology , Animals , Biopsy/methods , DNA, Viral/metabolism , Hepatocytes/cytology , Humans , Immunohistochemistry/methods , Kinetics , Liver/metabolism , Liver/virology , Mice , Mice, SCID , Viral Load
12.
Int J Pediatr Otorhinolaryngol ; 74(6): 586-90, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20381885

ABSTRACT

OBJECTIVE: Infants with a cleft palate and microscopical evidence for middle ear effusion attracted our attention because of normal tympanometry results and negative otoacoustic emissions. These contradictory findings initiated us to study to what extent high frequency tampynometry is able to supply us with more reliable results. METHODS: Eighty-three ears of 46 cleft palate babies aged between 2 and 7 months were examined within the pedaudiological screening procedure via tympanometry before their surgical cleft closure. We applied probe tone frequencies of 226 Hz and 678 Hz. A control cohort of 69 ears of 36 babies without cleft palate was established. Results were later compared to the intraoperative findings. RESULTS: By tympanometry with a 226-Hz probe tone, the examiners predicted the intraoperative findings correctly in only 29 cases of 83 examined ears (34.9%). However, their interpretation of tympanometry results by means of a 678-Hz probe tone correlated to the intraoperative findings in 96.3% cases. CONCLUSIONS: In cleft palate babies tympanometry with a 678-Hz probe tone yields clear evidence of middle ear effusion and should therefore serve as an essential instrument before the first surgical step of palate closure. In case of applying the 226-Hz probe tone, we were often confronted with normal function of the Eustachian tube despite of proved existence of middle ear effusion.


Subject(s)
Acoustic Impedance Tests/methods , Cleft Palate/physiopathology , Otitis Media with Effusion/complications , Otitis Media with Effusion/physiopathology , Cleft Palate/surgery , Humans , Infant , Otoacoustic Emissions, Spontaneous/physiology , Predictive Value of Tests , Preoperative Care , Prospective Studies
13.
Am J Otolaryngol ; 30(3): 145-9, 2009.
Article in English | MEDLINE | ID: mdl-19410116

ABSTRACT

We characterize 2 cases with sensorineural hearing loss and ophthalmologic findings. The clinicopathologic features revealed diagnosis of Susac's syndrome, a rare microangiopathy with cochlea, retinal, and brain affection. Diagnosis may be difficult because most specialists are not familiar with this angiopathy. However, the characteristic symptoms can mimic different pathologies, which may result in attention of radiologists, ophthalmologists, neurologists and otolaryngologists. In this report, we present 2 women with Susac's syndrome unveiled by audiometry, magnetic resonance imaging of the brain, and ophthalmologic findings. The course of the illness and a review of literature are presented.


Subject(s)
Brain Damage, Chronic/pathology , Encephalitis/pathology , Hearing Loss, Sensorineural/pathology , Retinal Artery Occlusion/pathology , Adult , Audiometry, Pure-Tone , Brain Damage, Chronic/complications , Brain Damage, Chronic/therapy , Diagnosis, Differential , Encephalitis/complications , Female , Fluorescein Angiography , Hearing Loss, Sensorineural/complications , Hearing Loss, Sensorineural/etiology , Humans , Magnetic Resonance Imaging , Retinal Artery Occlusion/complications , Syndrome , Tinnitus/etiology
14.
Anticancer Res ; 28(2A): 973-9, 2008.
Article in English | MEDLINE | ID: mdl-18507044

ABSTRACT

BACKGROUND: In order to elucidate the role of the receptor tyrosine kinase HER3, the expression characteristics in different tissues of cutaneous malignancies and in normal skin were compared. MATERIALS AND METHODS: In this study HER3 expression was evaluated by RT-PCR analysis and immunohistochemistry from different tissue specimens of cutaneous tumors like nevi, primary malignant melanomas, basal cell carcinoma, squamous cell carcinoma and malignant melanoma metastases and normal skin samples and graded into weak, moderate and strong expression. Associations of tumor thickness in these specimens with HER3 expressions were also analyzed. RESULTS: HER3 expression was found in 63% (10/16) of the basal cell carcinomas, in 4/5 of squamous cell carcinomas and in one Merkel cell carcinoma. Within the group of different malignant melanomas, HER3 expression was detected in 35% of the nodular malignant melanomas (6/17) and in 9/19 of the superficial spreading melanomas, including 2 lentigo malignant melanomas. The majority of melanomas with a higher tumor thickness expressed HER3, and 85% of melanoma metastasis were HER3-positive. CONCLUSION: HER3 expression was associated with hyperproliferate tumor stages and suggested that HER3 expression could reflect an increased malignant potential in cutaneous lesions.


Subject(s)
Skin Neoplasms/metabolism , Carcinoma, Basal Cell/genetics , Carcinoma, Basal Cell/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Humans , Immunohistochemistry , Melanoma/genetics , Melanoma/metabolism , Neoplasm Metastasis , Nevus , Receptor, ErbB-3/genetics , Receptor, ErbB-3/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Skin/metabolism , Skin Neoplasms/genetics
15.
Emerg Infect Dis ; 14(4): 545-51, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18394270

ABSTRACT

In 1988, the World Health Assembly launched the Global Polio Eradication Initiative, which aimed to use large-scale vaccination with the oral vaccine to eradicate polio worldwide by the year 2000. Although important progress has been made, polio remains endemic in several countries. Also, the current control measures will likely be inadequate to deal with problems that may arise in the postpolio era. A panel convoked by the National Research Council concluded that the use of antiviral drugs may be essential in the polio eradication strategy. We here report on a comparative study of the antipoliovirus activity of a selection of molecules that have previously been reported to be inhibitors of picornavirus replication and discuss their potential use, alone or in combination, for the treatment or prophylaxis of poliovirus infection.


Subject(s)
Antiviral Agents/pharmacology , Poliomyelitis/prevention & control , Poliovirus/drug effects , HeLa Cells , Humans , Poliomyelitis/drug therapy , Poliovirus/physiology , Protein Binding , Viral Proteins/antagonists & inhibitors , Viral Proteins/metabolism , Virus Replication/drug effects
16.
Biochem Biophys Res Commun ; 353(3): 628-32, 2007 Feb 16.
Article in English | MEDLINE | ID: mdl-17194441

ABSTRACT

Despite the fact that enteroviruses are implicated in a variety of human diseases, there is no approved therapy for the treatment of enteroviral infections. Here, a series of 2,6-dihalophenyl-substituted 1H,3H-thiazolo[3,4-a]benzimidazoles with anti-enterovirus activity is reported. The compounds elicit potent activity against coxsackievirus A9, echovirus 9 and 11 and all six strains of coxsackievirus B. A structure-activity relationship analysis revealed that the presence of substituents at position 6 of the tricyclic system positively influences the antiviral activity, whereas substitutions at position 7 are less favorable. In particular a 6-trifluoromethyl substitution leads to a substantial improvement of the antiviral activity as compared to the unsubstituted structure. Furthermore, an additional introduction of a 2-Cl, 6-F substitution on the phenyl at C-1 results in a further increase of the antiviral activity. Hence, 1-(2-chloro-6-fluorophenyl)-6-trifluoromethyl-1H,3H-thiazolo[3,4-a]benzimidazole results in a dose-dependent inhibition of viral replication with a 50% effective concentration (EC50) of 0.41 microg/ml without any detectable cytotoxicity at the highest concentration (100 microg/ml) tested.


Subject(s)
Antiviral Agents/pharmacology , Benzimidazoles/pharmacology , Enterovirus Infections/drug therapy , Thiazoles/pharmacology , Animals , Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Cell Survival/drug effects , Chlorocebus aethiops , HeLa Cells , Humans , Picornaviridae/drug effects , Structure-Activity Relationship , Thiazoles/therapeutic use , Vero Cells
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