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2.
R Soc Open Sci ; 11(10): 40962, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39386982

ABSTRACT

Conformational flexibility is one of the main disadvantages of peptide-based compounds. We focus on their molecular 'chameleonicity' related to forming pseudo-cyclic motifs via modulation of weak intramolecular interactions. It is an appealing strategy for controlling equilibrium between the polar open and the nonpolar closed conformations. Within this context, we report here the crystal structure of the (R)-(2-tert-butoxycarbonyl)amino-1-oxo-3-phenyl)propyl)-1-cyclopentene (1), synthesis of which in high yield was achieved by a facile multi-step protocol. Our Cambridge Structural Database (CSD) overview for the peptide-based crystals revealed the exclusivity of this compound from the viewpoint of the unusual pseudo-bicyclic system via C-H…O and C-O…π interactions, in which cyclopentene shields the amide bond. Notably, cyclopentene as a bioisostere of proline is an appealing scaffold in medicinal chemistry. An extensive combined experimental and computational study provided more profound insight into the supramolecular landscape of 1 with respect to similar derivatives deposited in the CSD, including the tendency of cyclopentene for the generation of pseudo-cyclic motifs through weak H-bonding and π-based intramolecular interactions. These weak interactions have been examined by either the quantum theory of 'atoms-in-molecules' (QTAIM) or complex Hirshfeld surface methodology, including enrichment ratios, molecular electrostatic potential surfaces and energy frameworks. In all analysed crystals, all types of H-bonded motifs involving cyclopentene are formed at all levels of supramolecular architecture. A library of cyclopentene-based H-bonding synthons is provided. A molecular docking study depicted vital interactions of cyclopentene with key amino acid residues inside the active sites of two prominent protein kinases, uncovering the therapeutic potential of 1 against breast cancer. To a large extent, dispersion forces have significance in stabilizing the supramolecular structure of both ligand and bio-complex ligand-protein. Finally, the satisfactory in silico bio-pharmacokinetic profile of 1 related to drug-likeness and blood-brain barrier permeation was also revealed.

3.
Pharmaceutics ; 16(8)2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39204451

ABSTRACT

The anti-inflammatory, antiviral, and anti-cancer properties, as well as the mechanism of action of cyclo-[Pro-Pro-ß3-HoPhe-Phe-] tetrapeptide (denoted as 4B8M), were recently described. The aim of this work was to synthesize and evaluate the immunosuppressive actions of the stereochemical variants of 4B8M by sequential substitution of L-amino acids by D-amino acids (a series of peptides denoted as P01-P07) using parent 4B8M as a reference compound. In addition, diverse available bioinformatics tools using machine learning and artificial intelligence were tested to find the bio-pharmacokinetic and polypharmacological attributes of analyzed stereomers. All peptides were non-toxic to human peripheral blood mononuclear cells (PBMCs) and only cyclo-[D-Pro-Pro-ß3-HoPhe-Phe-] peptide (P03) was capable of inhibiting mitogen-induced PBMC proliferation. The peptides inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) to various degrees, with P04 (cyclo-[Pro-Pro-D-ß3-HoPhe-Phe-]) and P03 being the most potent. For further in vivo studies, P03 was selected because it had the combined properties of inhibiting cell proliferation and TNF-α production. P03 demonstrated a comparable ability to 4B8M in the inhibition of auricle edema and lymph node cell number and in the normalization of a distorted blood cell composition in contact sensitivity to the oxazolone mouse model. In the mouse model of carrageenan-induced inflammation of the air pouch, P03 exhibited a similar inhibition of the cell number in the air pouches as 4B8M, but its inhibitory effects on the percentage of neutrophils and eosinophils in the air pouches and blood, as well as on mastocyte degranulation in the air pouches, were stronger in comparison to 4B8M. Lastly, in a mouse model of dextran sulfate-induced colitis, similar effects to 4B8M regarding thymocyte number restoration and normalization of the blood cell pictures by P03 were observed. In summary, depending on either experimental findings or in silico predictions, P03 demonstrated comparable, or even better, anti-inflammatory and bio-pharmacokinetic properties to 4B8M and may be considered as a potential therapeutic. The possibility of P00 and P03 identification by circular dichroism measurements was tested by quantum-chemical calculations.

4.
Cureus ; 16(7): e65716, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39211682

ABSTRACT

Fabry disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene, which lead to a deficiency of the alpha-galactosidase A enzyme. Pulmonary involvement is one of the possible manifestations of FD, but it is often overlooked and is rarely the only clinical presentation. Chronic cough is an uncommon and nonspecific symptom of pulmonary involvement in FD. Here, we report a case of a 46-year-old non-smoker, Caucasian male who presented to a general practitioner with chronic cough without a significant medical history. The patient was referred to our hospital after routine blood tests revealed elevated creatinine levels. As his cousin had end-stage chronic kidney disease due to FD, we performed a fluorometric assay of the alpha-galactosidase A activity in dried blood spots, which showed abnormal results. Eventually, genetic testing revealed a mutation in the GLA gene. As respiratory symptoms persisted during hospitalization, spirometry was performed, revealing an obstructive pattern. Furthermore, bronchoscopy showed nonspecific bronchial inflammation. Additionally, end-stage renal disease and hypertrophic cardiomyopathy were diagnosed. The patient was put on enzyme replacement therapy, and underwent kidney transplantation. Despite all these procedures, we did not observe any improvement in his cough. This case highlights that chronic cough may be an important clue for pulmonary involvement in FD and should prompt further evaluation in patients with other features suggestive of FD. Early diagnosis and treatment are essential for improving the outcome and quality of life in patients with FD.

8.
J Interv Card Electrophysiol ; 67(3): 493-501, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37505337

ABSTRACT

BACKGROUND: Cryoballoon ablation is a well-established anatomical approach for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Although widely adopted, regional variations in standards of care have not been well characterized. METHODS: Patients with AF were enrolled in the Cryo Global Registry (NCT02752737) from May 2016 to Sept 2021 at 128 sites in 37 countries and treated with cryoballoon ablation according to local clinical practice. Baseline patient and procedural characteristics were summarized for 8 regions (Central Asia & Russia, East Asia, Europe, Middle East, North America, South Africa, South America, and Southeast Asia). Serious procedure-related adverse events (SAEs) were evaluated in a subset of patients with ≥ 7 days of follow-up. RESULTS: A total of 3,680 patients undergoing initial PVI for AF were included. Cryoballoon ablation was commonly performed in patients with paroxysmal AF. Mean age ranged from 47 ± 12 years in the Middle East to 64 ± 11 years in East Asia. Mean procedure time was ≤ 95 min in all regions. Average freeze duration ranged from 153 ± 41 s in Southeast Asia to 230 ± 29 s in Central Asia & Russia. Acute procedural success was ≥ 94.7% in all geographies. In 3,126 subjects with ≥ 7 days of follow-up, 122 procedure-related SAEs were reported in 111 patients (3.6%) and remained low in all regions. One procedure-related death was reported during data collection. CONCLUSIONS: Despite regional variations in patient selection and procedural characteristics, PVI using cryoballoon ablation was performed with high acute success and short procedural times around the world. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02752737.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Cryosurgery , Pulmonary Veins , Humans , Adult , Middle Aged , Treatment Outcome , Patient Selection , Cryosurgery/methods , Registries , Pulmonary Veins/surgery , Catheter Ablation/methods , Recurrence
9.
J Neurochem ; 2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37791997

ABSTRACT

Neuropsychiatric conditions represent a major medical and societal challenge. The etiology of these conditions is very complex and combines genetic and environmental factors. The latter, for example, excessive maternal or early postnatal inflammation, as well as various forms of psychotrauma, often act as triggers leading to mental illness after a prolonged latent period (sometimes years). Matrix metalloproteinase-9 (MMP-9) is an extracellularly and extrasynaptic operating protease that is markedly activated in response to the aforementioned environmental insults. MMP-9 has also been shown to play a pivotal role in the plasticity of excitatory synapses, which, in its aberrant form, has repeatedly been implicated in the etiology of mental illness. In this conceptual review, we evaluate the experimental and clinical evidence supporting the claim that MMP-9 is uniquely positioned to be considered a drug target for ameliorating the adverse effects of environmental insults on the development of a variety of neuropsychiatric conditions, such as schizophrenia, bipolar disorder, major depression, autism spectrum disorders, addiction, and epilepsy. We also identify specific challenges and bottlenecks hampering the translation of knowledge on MMP-9 into new clinical treatments for the conditions above and suggest ways to overcome these barriers.

10.
Adv Clin Exp Med ; 32(11): 1249-1256, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37078411

ABSTRACT

BACKGROUND: Transvenous lead extraction (TLE) is recommended in cases of local and systemic infections related to cardiac implantable electronic devices (CIEDs). Additionally, TLE is indicated in the event of lead damage or CIED malfunction. The extraction procedure is associated with a risk of life-threatening complications. OBJECTIVES: The aim of the EVO registry was to assess the safety and efficacy of birotational Evolution tool usage. MATERIAL AND METHODS: This registry study was prospectively conducted in 8 high-volume implantation centers in Poland. The study included 133 patients aged 63.5 ±15.1 years, and 76.69% were male. Indications for the procedure were: local or systemic infection (33.1%) and lead dysfunction (66.9%). The number of leads extracted varied from 1 (39.84%) to 3 (9.77%). RESULTS: Clinical procedural success was achieved in 99.1% of cases. A total of 226 leads were extracted, and 206 used the Evolution system. Two procedural strategies were identified while using the Evolution system: (1) usage of locking stylet, propylene sheaths and the Evolution system (118 leads, 52%) - group A; (2) usage of locking stylet and Evolution (88 leads, 39%) - group B. There were no differences in the number of complications between these 2 groups. The extraction time was significantly shorter (p = 0.02) in group B than in group A. Major complications occurred in 5.2% of cases with 2 intraprocedural deaths. Minor complications occurred in 1.5% of patients. CONCLUSIONS: The registry confirmed the efficacy and relative safety of the birotational Evolution sheath. Using the rotational sheath as a first attempt significantly reduces extraction time without compromising its safety.


Subject(s)
Defibrillators, Implantable , Pacemaker, Artificial , Aged , Female , Humans , Male , Middle Aged , Defibrillators, Implantable/adverse effects , Device Removal , Employment , Pacemaker, Artificial/adverse effects , Prospective Studies , Registries , Retrospective Studies , Treatment Outcome
11.
Kardiol Pol ; 81(5): 455-462, 2023.
Article in English | MEDLINE | ID: mdl-36871295

ABSTRACT

BACKGROUND: The use of subcutaneous implantable cardioverter-defibrillators (S-ICD) has been growing in Poland since 2014. The Polish Registry of S-ICD Implantations was run by the Heart Rhythm Section of the Polish Cardiac Society between May 2020 and September 2022 to monitor the implementation of that therapy in Poland. AIMS: To investigate and present the state-of-the-art of S-ICD implantation in Poland. METHODS: Implanting centers reported clinical data of patients undergoing S-ICD implantations and replacements, including age, sex, height, weight, underlying disease, history of pacemaker and defibrillator implantations, indications for S-ICD, electrocardiographical parameters, procedural techniques, and complications. RESULTS: Four hundred and forty patients undergoing S-ICD implantation (411) or replacement (29) were reported by 16 centers. Most patients were in New York Heart Association class II (218 patients, 53%) or I (150 patients, 36.5%). Left ventricular ejection fraction was 10%-80%, median (IQR) was 33% (25%-55%). Primary prevention indications were present in 273 patients (66.4%). Non-ischemic cardiomyopathy was reported in 194 patients (47.2%). The main reason for the choice of S-ICD were: young age (309, 75.2%), risk of infectious complications (46, 11.2%), prior infective endocarditis (36, 8.8%), hemodialysis (23, 5.6%), and immunosuppressive therapy (7, 1.7%). Electrocardiographic screening was performed in 90% of patients. The rate of adverse events was low (1.7%). No surgical complications were observed.


Subject(s)
Defibrillators, Implantable , Humans , Poland , Defibrillators, Implantable/adverse effects , Stroke Volume , Ventricular Function, Left , Registries , Death, Sudden, Cardiac/prevention & control
12.
Europace ; 25(5)2023 05 19.
Article in English | MEDLINE | ID: mdl-36916199

ABSTRACT

AIMS: The field of conduction system pacing (CSP) is evolving, and our aim was to obtain a contemporary picture of European CSP practice. METHODS AND RESULTS: A survey was devised by a European CSP Expert Group and sent electronically to cardiologists utilizing CSP. A total of 284 physicians were invited to contribute of which 171 physicians (60.2%; 85% electrophysiologists) responded. Most (77%) had experience with both His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Pacing indications ranked highest for CSP were atrioventricular block (irrespective of left ventricular ejection fraction) and when coronary sinus lead implantation failed. For patients with left bundle branch block (LBBB) and heart failure (HF), conventional biventricular pacing remained first-line treatment. For most indications, operators preferred LBBAP over HBP as a first-line approach. When HBP was attempted as an initial approach, reasons reported for transitioning to utilizing LBBAP were: (i) high threshold (reported as >2 V at 1 ms), (ii) failure to reverse bundle branch block, or (iii) > 30 min attempting to implant at His-bundle sites. Backup right ventricular lead use for HBP was low (median 20%) and predominated in pace-and-ablate scenarios. Twelve-lead electrocardiogram assessment was deemed highly important during follow-up. This, coupled with limitations from current capture management algorithms, limits remote monitoring for CSP patients. CONCLUSIONS: This survey provides a snapshot of CSP implementation in Europe. Currently, CSP is predominantly used for bradycardia indications. For HF patients with LBBB, most operators reserve CSP for biventricular implant failures. Left bundle branch area pacing ostensibly has practical advantages over HBP and is therefore preferred by many operators. Practical limitations remain, and large randomized clinical trial data are currently lacking.


Subject(s)
Cardiac Resynchronization Therapy , Heart Failure , Humans , Stroke Volume/physiology , Ventricular Function, Left , Treatment Outcome , Heart Conduction System , Bundle-Branch Block/diagnosis , Bundle-Branch Block/therapy , Arrhythmias, Cardiac/therapy , Heart Failure/diagnosis , Heart Failure/therapy
13.
Article in English | MEDLINE | ID: mdl-36429615

ABSTRACT

Infections with Borrelia may cause cardiac conduction system abnormalities, including atrioventricular blocks (AVBs). Therefore, we aimed to identify patients in whom Lyme carditis (LC) could be considered as the initial diagnosis among consecutive subjects who were referred for implantation of a permanent pacemaker due to symptomatic AVBs. To date, such a systematic evaluation has not been reported yet. Validation of the Suspicious Index for Lyme Carditis (SILC) in our study population was considered as an additional goal. We investigated consecutive patients with AVB admitted to our department for a pacemaker implantation. Serological diagnostic tests against Borrelia burgdorferi sensu lato (Bbsl) were performed in those with no obvious cardiac causes of AVB. The final study population consisted of 130 patients (80 M, mean age 67.4 ± 17.6). Lyme carditis was assumed as the initial diagnosis in 16 patients (12%) based on ABV and IgM Bbsl seropositivity. The patients with LC were younger and more frequently manifested constitutional symptoms of infection and fluctuating AVB. The highest prognostic value for identification of LC patients was obtained for the modified SILC, which included the following parameters: (1) age lower than 75 years; (2) risky outdoor activity and living in the countryside; (3) tick bite; (4) constitutional symptoms of Lyme disease; (5) erythema migrans; (6) male sex and (7) fluctuating atrioventricular block. We concluded that diagnostics for LC should be routinely considered in patients with advanced AVB. Modified SILC may identify the patients at risk of LC.


Subject(s)
Atrioventricular Block , Borrelia burgdorferi , Lyme Disease , Myocarditis , Humans , Male , Middle Aged , Aged , Aged, 80 and over , Atrioventricular Block/epidemiology , Atrioventricular Block/etiology , Prevalence , Myocarditis/epidemiology , Myocarditis/etiology , Lyme Disease/complications , Lyme Disease/diagnosis , Lyme Disease/epidemiology
14.
Pol Merkur Lekarski ; 50(299): 282-286, 2022 Oct 21.
Article in Polish | MEDLINE | ID: mdl-36283009

ABSTRACT

Myocardial infarction (MI) of the right ventricle (RV) coexists in 20- 60% of patients with inferior MI. There are electrocardiographic indicators which are connected with RV MI, which may also predict unfavorable clinical outcome of in-hospital follow-up. AIM: The aim of the study was determination a value of seven electrocardiographic predictors of RV MI in prognosis of in-hospital complications in patients with inferior MI. MATERIALS AND METHODS: The analysis of hospital files of patients admitted with diagnosis of inferior MI with persistent ST elevation (STEMI) was retrospectively performed. A set of seven RV MI predictors (RVMIP) was assessed from the electrocardiographic tracings (ECG). Finally in group of 167 patients relation between each RVMIP and in-hospital complications was statistically evaluated. RESULTS: The most often RVMIP was an elevation of ST higher in III lead then in II and aVF (RVMIP-2; recorded in 61,7% patients). In total any RVMIP was found in ECG of 142 patients (85%). Patients who had more RVMIP were more prone for combined adverse cardiac event (CACE, which included artificial respirotherapy, lungs edema and cardiogenic shock) (p=0,012); ventricular arrhythmias (p<0,001) and second/third grade atrioventricular blocks (p=0,028). Advanced atrioventricular blocks were more often observed in patient with ST elevation in V1 and ST depression in aVL (OR=4,91, p=0,005; OR=4,67, p=0,006; respectively). On the other hand second/third grade atrioventricular blocks were also related to higher incidence of CACE, ventricular arrhythmias and atrial fibrillation (AF), respectively: OR=8,1, p<0,001; OR=7,19, p=0,001; OR=5,75, p=0,001). CONCLUSIONS: The more RVMIPs the higher risk of in-hospital complication in patients with inferior MI. The second/third grade atrioventricular blocks were recorded more often in patients with ST elevation in V1 and ST depression in aVL. Advanced atrioventricular conduction blocks were related to worse outcome of in-hospital followup. A detailed ECG analysis in admission still adds important contribution in determination of in-hospital risk of complications.


Subject(s)
Atrioventricular Block , Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , Retrospective Studies , Electrocardiography , Arrhythmias, Cardiac
15.
Sci Rep ; 12(1): 17263, 2022 10 14.
Article in English | MEDLINE | ID: mdl-36241660

ABSTRACT

The devastating Varroa mite (Varroa destructor Anderson and Trueman) is an obligatory ectoparasite of the honey bee, contributing to significant colony losses in North America and throughout the world. The limited number of conventional acaricides to reduce Varroa mites and prevent disease in honey bee colonies is challenged with wide-spread resistance and low target-site selectivity. Here, we propose a biorational approach using comparative genomics for the development of honey bee-safe and selective acaricides targeting the Varroa mite-specific neuropeptidergic system regulated by proctolin, which is lacking in the honey bee. Proctolin is a highly conserved pentapeptide RYLPT (Arg-Tyr-Leu-Pro-Thr) known to act through a G protein-coupled receptor to elicit myotropic activity in arthropod species. A total of 33 different peptidomimetic and peptide variants were tested on the Varroa mite proctolin receptor. Ligand docking model and mutagenesis studies revealed the importance of the core aromatic residue Tyr2 in the proctolin ligand. Peptidomimetics were observed to have significant oral toxicity leading to the paralysis and death of Varroa mites, while there were no negative effects observed for honey bees. We have demonstrated that a taxon-specific physiological target identified by advanced genomics information offers an opportunity to develop Varroa mite-selective acaricides, hence, expedited translational processes.


Subject(s)
Acaricides , Peptidomimetics , Varroidae , Acaricides/pharmacology , Animals , Bees/genetics , Genomics , Ligands , Peptidomimetics/pharmacology , Varroidae/physiology
16.
Front Nutr ; 9: 957256, 2022.
Article in English | MEDLINE | ID: mdl-35967783

ABSTRACT

Background: One of tools to tackle growing problem of overweight and obesity are the taxation mechanisms applied to sugar-sweetened beverages, which are expected to influence the common eating behaviors, but also they have impact on the market and public finances. The solution is therefore highly entangled in the complex of social and intersectoral interests generating a number of opportunities and threats affecting its feasibility. Aims: The study aims to depict the views of Polish stakeholders on the implementation of the sugar tax in Poland, particularly the perception of success determinants, barriers, as well as views on the features of the implemented solutions and possible alternatives. Methods: We used semi-structured interviews with 18 individuals representing key public health stakeholders in Poland. The interview consisted of four parts, where first concentrated on the advantages and disadvantages of the SSB tax, the second part explored stakeholder involvement and stances, third concerned the feasibility of the project, and in the fourth part respondents were asked for suggestions for decision-makers regarding the content of the project and its implementation process. To reconstruct position of 4 main political parties we applied desk research. We used MAXQDA v2020 to analyse the collected data. Results: Stakeholders tend to expressed conflicting views on the effectiveness, relevance and socio-economic impact of the SSB tax. All of them agreed that the tax may appear severe for the poorest groups, children and adolescents, while disagreeing about the economic impact of the levy. The allocation of additional tax revenues was raising doubts, with stakeholders believing that the fiscal aim is the basic reason for implementing the tax, while these resources should be primarily dedicated to health promotion intervention and prevention of diet-related diseases. On the other hand, the political debate on the tax was highly superficial with strong populism arising of the presented positions. Conclusions: There is a need to conduct a thorough public debate and improvements in terms of public communication to increase social awareness, sealing and refining the implemented solutions. Close cooperation with market players and non-governmental organizations is highly recommended.

17.
Int J Mol Sci ; 23(13)2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35806175

ABSTRACT

Short peptides have great potential as safe and effective anticancer drug leads. Herein, the influence of short cyclic peptides containing the Pro-Pro-Phe-Phe sequence on patient-derived melanoma cells was investigated. Cyclic peptides such as cyclo(Leu-Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe-), called CLA, and cyclo(Pro-homoPro-ß3homoPhe-Phe-), called P11, exert the cytotoxic and the cytostatic effects in melanoma cells, respectively. CLA was the most active peptide as it reduced the viability of melanoma cells to 50% of control at about 10 µM, whereas P11 at about 40 µM after 48 h incubation. Interestingly, a linear derivative of P11 did not induce any effect in melanoma cells confirming previous studies showing that cyclic peptides exert better biological activity compared to their linear counterparts. According to in silico predictions, cyclic tetrapeptides show a better pharmacokinetic and toxic profile to humans than CLA. Notably, the spatial structure of those peptides containing synthetic amino acids has not been explored yet. In the Cambridge Structural Database, there is only one such cyclic tetrapeptide, cyclo((R)-ß2homoPhe-D-Pro-Lys-Phe-), while in the Protein Data Bank-none. Therefore, we report the first crystal structure of cyclo(Pro-Pro-ß3homoPhe-Phe-), denoted as 4B8M, a close analog of P11, which is crucial for drug discovery. Comparative molecular and supramolecular analysis of both structures was performed. The DFT findings revealed that 4B8M is well interpreted in the water solution. The results of complex Hirshfeld surface investigations on the cooperativity of interatomic contacts in terms of electrostatic and energetic features are provided. In short, the enrichment ratio revealed O…H/H…O and C…H/H…C as privileged intercontacts in the crystals in relation to basic and large supramolecular H-bonding synthon patterns. Furthermore, the ability of self-assemble 4B8M leading to a nanotubular structure is also discussed.


Subject(s)
Melanoma , Peptides, Cyclic , Dipeptides , Humans , Melanoma/drug therapy , Peptides , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology
18.
Am J Case Rep ; 23: e935259, 2022 Jul 29.
Article in English | MEDLINE | ID: mdl-35905036

ABSTRACT

BACKGROUND Cardiac inflammatory pseudotumors are rarely observed. Their etiology might include immunologic abnormalities, fibrogenetic disorders, specific reactions to infections or abnormalities related to trauma, necrosis, or neoplasm. Life-threatening ventricular tachycardia and cases of sudden death related to cardiac tumors have been reported. The present report describes and discusses diagnostic and therapeutic solutions for the treatment of nonsarcoid multiorgan pseudotumors with cardiac involvement. CASE REPORT A 38-year-old woman presented to the clinic with symptomatic ventricular tachycardia. As coronary artery disease, cardiomyopathy, and channelopathy were ruled out, and electrocardiograms were not typical of idiopathic arrhythmia, the patient underwent detailed diagnostics which included targeted endomyocardial biopsy, which revealed a cardiac inflammatory pseudotumor. Laborious testing (and eventually, antibiotic therapy) led to ex juvantibus diagnosis of multiorgan disseminated brucellosis with cardiac involvement. Treatment with ceftriaxone, doxycycline, and rifampicin resulted in a complete resolution of all lesions after 3 months, and sustained recovery was observed during a 5-year follow-up. As the risk of ventricular tachycardia could not be reliably predicted, the patient had a subcutaneous implantable cardioverter-defibrillator implanted. CONCLUSIONS A vast diagnostic armamentarium of modern medicine allowed us to diagnose an unsuspected and rare cardiac inflammatory pseudotumor. In the case of travelers, the possibility of regionally specific illnesses, especially infections, must be taken into consideration as possible causes of arrhythmias. Cardiac magnetic resonance imaging may be useful in patients with 'idiopathic ventricular tachycardias' to detect non-apparent myocardial lesions which may result from the underlying cause of the arrhythmia.


Subject(s)
Brucellosis , Defibrillators, Implantable , Granuloma, Plasma Cell , Heart Neoplasms , Tachycardia, Ventricular , Adult , Arrhythmias, Cardiac/diagnosis , Brucellosis/complications , Brucellosis/diagnosis , Female , Granuloma, Plasma Cell/diagnosis , Granuloma, Plasma Cell/therapy , Humans , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/therapy
19.
Molecules ; 27(11)2022 May 31.
Article in English | MEDLINE | ID: mdl-35684487

ABSTRACT

The core of Cyclolinopeptide A (CLA, cyclo(LIILVPPFF)), responsible for its high immunosuppressive activity, contains a Pro-Pro-Phe-Phe sequence. A newly synthesized cyclic tetrapeptide, cyclo(Pro-Pro-ß3-HoPhe-Phe) (denoted as 4B8M) bearing the active sequence of CLA, was recently shown to exhibit a wide array of anti-inflammatory properties in mouse models. In this investigation, we demonstrate that the peptide significantly inhibits the replication of human adenovirus C serotype 5 (HAdV-5) and Herpes simplex virus type-1 (HSV-1) in epithelial lung cell line A-549, applying Cidofovir and Acyclovir as reference drugs. Based on a previously established mechanism of its action, we propose that the peptide may inhibit virus replication by the induction of PGE2 acting via EP2/EP4 receptors in epithelial cells. In summary, we reveal a new, antiviral property of this anti-inflammatory peptide.


Subject(s)
Herpesvirus 1, Human , Animals , Antiviral Agents/pharmacology , Dipeptides , Immunosuppressive Agents/pharmacology , Mice , Peptides , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology
20.
Molecules ; 27(11)2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35684571

ABSTRACT

It is beyond doubt that short peptides hold significant promise in bio-medicine, as the most versatile molecules, both structurally and functionally [...].


Subject(s)
Medicine , Peptides , Peptides/chemistry
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