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Hepatic fibrosis is a common consequence of chronic liver diseases and necessitates accurate evaluation for optimal patient management. Traditional liver biopsy, the gold standard for fibrosis assessment, is invasive and can be associated with complications. Lately, considerable progress has been made in developing noninvasive markers for liver fibrosis evaluation.This comprehensive review presents a systematic analysis of the current noninvasive markers for hepatic fibrosis assessment. Serological markers, imaging techniques and novel technologies are thoroughly evaluated for their diagnostic accuracy and clinical applicability.The advantages and limitations of each noninvasive marker are discussed, highlighting their potential to replace or complement liver biopsy. Moreover, challenges and opportunities in standardization, validation, and clinical implementation of these markers are addressed.In conclusion, noninvasive markers play a significant role in hepatic fibrosis evaluation. As reliable alternatives to liver biopsy, these markers have the potential to enhance patient care, streamline disease monitoring, and drive personalized treatment strategies in liver diseases associated with fibrosis. However, further research and validation studies are required to establish their widespread use in routine clinical practice.

Background and Objectives: Fibrillinopathies have different phenotypic expression: Marfan-like skeleton features, MLSF; mitral valve prolapse syndrome, MVPS; MASS phenotype, M = mitral valve prolapse, MVP, A = aortic root dilation, S = skeletal features, and the second S = (cutaneous) striae; Marfan Syndrome, MS. The study had the following main objectives: the correlation between disc displacement, DD (a major sign for temporomandibular joint dysfunction, TMDs) on magnetic resonance imaging, MRI, and aortic Z score (a major sign for aortic root dilation) on echocardiography; the predictive value of DD towards aortic Z score. DD had 2 types of severity: DD with reduction (the mild type, DDwR), and DD without reduction (the severe type, DDwoR). Materials and Methods: The type of fibrillinopathy was precised by clinical exam (systemic score), ophthalmic exam (for ectopia lentis), and echocardiography (aortic Z score, MVP). Medical treatment consisted of betablockers, BB (for patients with tachycardia), or angiotensin II receptor blockers, ARB. Surgical treatment was addressed to aortic root aneurysm, and severe mitral regurgitation, MR. DD benefited from dental conservatory treatment or surgical restoration. Results: DD-Z score had a powerful correlation in MASS (Rho = 0.787, p < 0.01), and in MS patients (Rho = 0.819, p < 0.01). For the entire sample, both DDwR-Z score and DDwoR-Z score had a moderate correlation (Rho = 0.469, and respectively 0.669). Furthermore, DD was an important predictor for Z score. DDwoR had a double power of prediction for the Z score compared with DDwR (B coefficient = 1.661 for DDwR and 3.281 for DDwoR). Conclusions: TMDs had a powerful correlation with aortic root dilation in MASS and MS patients from the sample. Likewise, TMDs was a major predictor for aortic root dilation, in the entire sample. In clinical practice, we can utilize an extracardiac finding, TMDs, obtained by a non-invasive technique, MRI, for cardiac severity stratification of fibrillinopathies.

Ewing's sarcoma is a rare type of bone malignancy that occurs mostly in the bones of the pelvis and the limbs. We report a case of Ewing's sarcoma developed in the peroneal bone of a 10-year-old boy, with a severe affectation of the bone and pulmonary metastasis. Chemotherapy was administered to the patient. Approximately two years after first presentation, radiological exams indicated a nearly complete regenerated fibula and PET-CT scan indicated an inactive right lung mass. This case showed the incredible potency of recovery in pediatric patients and highlights the need for a personalized approach in pediatric orthopedic oncology. [ABSTRACT FROM AUTHOR]

In the light of growing concerns faced by Western societies due to aging, natality decline, and epidemic of cardio-metabolic diseases, both preventable and treatable, new and effective strategical interventions are urgently needed in order to decrease their socio-economical encumbrance. The recent focus of research has been redirected towards investigating the potential of haskap (Lonicera caerulea L.) as a novel functional food or superfruit. Therefore, our present review aims to highlight the latest scientific proofs regarding the potential of Lonicera caerulea L. (LC), a perennial fruit-bearing plant rich in polyphenols, in reversing cardio-metabolic dysfunctions. In this regard, a systematic search on two databases (PubMed and Google Scholar) from 1 January 2016 to 1 December 2023 was performed, the keyword combination being Lonicera caerulea L. AND the searched pharmacological action, with the inclusion criteria consisting of in extenso original articles, written in English. The health-enhancing characteristics of haskap berries have been examined through in vitro and in vivo studies from the 35 included original papers. Positive effects regarding cardiovascular diseases and metabolic syndrome have been assigned to the antioxidant activity, hypolipidemic and hypoglycemic effects, as well as to the hepatoprotective and vasoprotective potential. Latest advances regarding LCF mechanisms of action are detailed within this review as well. All these cutting-edge data suggest that this vegetal product would be a good candidate for further clinical studies.

Smoking and diabetes mellitus have been recognized as significant modifying factors of the evolution of periodontitis, being considered at the moment as descriptive factors in the periodontitis grading system. The purpose of this study was to assess the consequence of smoking, type 2 diabetes, and the combination of these two factors on clinical periodontal parameters, on the levels of gingival crevicular fluid (GCF), and also on ratios of pro-inflammatory and anti-inflammatory cytokines by using a commercially available kit-based multiplex fluorescent immunoassay. The study was carried out on 124 volunteers (control (C) group = 29, diabetes mellitus (DM) group = 32, smoking (S) group = 31, and S + DM group = 32). Total mean bleeding on probing was significantly lower in the S and S + DM groups, compared to that of the other groups (p < 0.05). Total amounts of TGF-β, MIP-1α, IL-6, IL-2, and IL-17 were significantly increased in the periodontally healthy sites of diabetes patients (p < 0.05), compared to those of the controls. Systemically healthy smoking patients had higher values of GM-CSF, TGF-β, IL-4, TNF-α, IL-5, and IL-7, while diabetic smoking patients showed higher values of IL-4, TGF-β, and MIP-1α. In smoking and systemically healthy patients, IL-23, IL-7, and IL-12 showed increased concentrations, while concentrations of TGF-β, MIP-1α, IL-2, IL-7, IL-12, IL-17, IL-21, and IL-23 were higher in smoking DM patients. In conclusion, in our study, diabetes mellitus induced a general pro-inflammatory state, while smoking mainly stimulated immunosuppression in the periodontal tissues of periodontitis subjects. [ABSTRACT FROM AUTHOR]

Introduction: Hip arthroplasty conducted through either cemented or cementless prostheses must alleviate pain and restore joint mobility and muscle strength. The main goal is to restore mobility, stability and to maintain ADL (Activities of Daily Living) within normal parameters. Current surgical techniques allow for state-of-the-art surgeries to be performed. Yet, the postop-erative course is strongly influenced by both pre-and postoperative psychological factors, as well as by associated diseases. Materials and Methods: We present the case of a 79-year-old female patient from Iasi, a retired yet still physically active gym teacher who was admitted an emergency to the Orthopedics Clin-ic of the ”Sf. Spiridon” Emergency Hospital with a displaced left femoral neck fracture resulting from same-level fall. The patient had for 6 years a Scorpio-Stryker cemented knee prosthesis on the same leg. Through surgical intervention, a cementless bipolar Lépine prosthesis was inserted into the left hip. Then, the patient presented to the Department of Physical Medicine and Reha-bilitation of the Iasi Clinical Railroad Hospital to receive an adequate post-operative rehabili-tation program. Results: The psychosocial factors have been analyzed with the help of various recent and spe-cialized psychological scales. The obtained results confirm the fact that these factors significantly influence the rehabilitation of prosthesis-wearing patients. Conclusion: Our study emphasizes the psychological impact on standing and walking rehabili-tation in a patient with two prostheses on the same motor axis

Introduction: Low back pain is a frequent condition, associated as a symptom with a multitude of organic or non-organic pathologies, resulting in the appearance of disability generating negative economic and soc-professional consequences. Being a relatively common symptom among patients, we created this paper with the aim to high-light the importance of the clinical examination along with the correct direction of the patient to a profile depart-ment, the review of differential diagnoses, as well as the establishment of a particular recovery plan adapted to each case. Materials and Methods: We analyzed a series of recent articles using the PubMed and the Cochrane Library data-bases ,using the keywords words “low back pain” and “rehabilitation”, to obtain data on the clinical and paraclinical examination, positive and differential diagnosis of chronic low back pain, as well as on rehabilitation management. Results: Low back pain may appear due to vertebral conditions (inflammatory, infectious, traumatic, neoplastic, degenerative, metabolic), or due to extravertebral causes. Along with the anamnesis, clinical examination and im-agistic investigations, we establish the positive diag-nosis and create an individualised rehabilitation plan. The reha-bilitation protocol is divided into stages , the final goal is to minimize the ischemia-pain-contracture chain. Conclusion: The pathology of the lumbosacral spine can be characterized by the word "diversi-ty", being one of the causes of early disability of the population in the field of work. Our work highlights the importance of the clinical and paraclinical examination in outlining the differen-tial diagnosis of chronic lumbar pain, as well as the role of the multidisciplinary team in com-plex individualized rehabilitation treatment.

The article presents a clinical case of the use of mycophenolate mofetil in a patient with high activity of systemic lupus erythematosus (SLE) and suppression of hematopoietic systems. The patient had all the characteristic signs of a severe course of SLE with the development of a complication - severe anemia (frequent exacerbations of the main disease, a significant and constant decrease in the number of erythrocytes and the level of hemoglobin in the general blood test against the background of glucocorticosteroid therapy, the severity of clinical symptoms). Damage to the hematopoietic system is characteristic of such patients and prevailed in the clinical picture of the disease and became the direct reason for seeking medical help. The appointment of mycophenolate mofetil made it possible to reduce the activity of manifestations of the main disease, reduce the development of possible complications, and in the future achieve clinical and laboratory remission. The clinical feature of this case is the effective use of mycophenolate mofetil in a patient with high activity of the course of SLE and the constant occurrence of a severe complication - severe anemia, against the background of glucocorticoid therapy. Damage to the hematopoietic system in the patient prevailed in the clinical picture of the disease and became the direct reason for seeking medical help. According to the literature, the use of mycophenolate mofetil in patients gives a positive clinical result in the treatment of such patients: reducing the activity of the course of the main disease, preventing complications, extending the period of clinical and laboratory remission. This approach will improve the quality of life of patients with this group of diseases with the additional advantage of reducing the burden on health care due to the reduction in the frequency of hospitalizations of patients with severe SLE.

The Acipenser ruthenus (Linnaeus, 1758), albino variety, in the second summer rearing to Brates sturgeons station from Galati was experimented. A number of 513 one year old sterlet were stocked in three Ewos fibreglass tanks, at an individual mean weight of 40 g and total length of 20 cm, in the first day of June 2007. The experiment had extended on 165 days, until half of November. During experimental tries the fishes were monitoring permanently and the essential parameters of technological water (dissolved oxygen, pH and temperature evolution) were checked and recorded. Feeding was achieved with commercial granular food and the conversion coefficient recorded was 1,3. Final body mean weight of sterlet was 130 g/ex. and the average length of 30 cm; the specific growth rate was 0,55g/day., i.e. 90 g/ex, and the survival percent recorded was 89,08 %.

Hepatitis C virus (HCV) infection is a major global health concern, with a significant risk of developing hepatocellular carcinoma (HCC) in infected individuals. The advent of oral antiviral therapy has revolutionized the management of HCV, achieving sustained virologic response (SVR) rates and reducing the risk of HCC. However, some patients still remain at risk for HCC even after successful antiviral treatment. Scoring systems have emerged as valuable tools to predict HCC risk and assist in post-treatment surveillance. This review aims to summarize and evaluate the existing scoring systems developed to assess HCC risk in HCV patients after oral antiviral therapy. We systematically searched relevant databases for published articles. We included studies that focused on the development, validation, and clinical application of scoring models for HCC risk prediction. We identified scoring systems, utilizing different variables such as demographic data, liver function tests, imaging findings, and genetic markers. We discuss the strengths and limitations of each scoring system and compare their predictive accuracy. Furthermore, we explore the potential for combining multiple scoring models to enhance risk stratification. The findings of this review highlight the utility of scoring systems in identifying patients at higher risk of developing HCC despite achieving SVR with oral antiviral therapy. Additionally, we discuss the implications of these scoring systems for clinical practice, risk stratification, and long-term surveillance of HCV patients. In conclusion, scoring systems offer a valuable approach to estimate the risk of HCC in HCV patients post oral antiviral treatment. A better understanding of these scoring models will help clinicians in tailored follow-up strategies and early detection of HCC, ultimately improving patient outcomes. Further research is needed to refine and validate these scoring systems in different populations and to explore their potential inclusion into clinical guidelines.

Smoking and diabetes mellitus have been recognized as significant modifying factors of the evolution of periodontitis, being considered at the moment as descriptive factors in the periodontitis grading system. The purpose of this study was to assess the consequence of smoking, type 2 diabetes, and the combination of these two factors on clinical periodontal parameters, on the levels of gingival crevicular fluid (GCF), and also on ratios of pro-inflammatory and anti-inflammatory cytokines by using a commercially available kit-based multiplex fluorescent immunoassay. The study was carried out on 124 volunteers (control (C) group = 29, diabetes mellitus (DM) group = 32, smoking (S) group = 31, and S + DM group = 32). Total mean bleeding on probing was significantly lower in the S and S + DM groups, compared to that of the other groups (p < 0.05). Total amounts of TGF-β, MIP-1α, IL-6, IL-2, and IL-17 were significantly increased in the periodontally healthy sites of diabetes patients (p < 0.05), compared to those of the controls. Systemically healthy smoking patients had higher values of GM-CSF, TGF-β, IL-4, TNF-α, IL-5, and IL-7, while diabetic smoking patients showed higher values of IL-4, TGF-β, and MIP-1α. In smoking and systemically healthy patients, IL-23, IL-7, and IL-12 showed increased concentrations, while concentrations of TGF-β, MIP-1α, IL-2, IL-7, IL-12, IL-17, IL-21, and IL-23 were higher in smoking DM patients. In conclusion, in our study, diabetes mellitus induced a general pro-inflammatory state, while smoking mainly stimulated immunosuppression in the periodontal tissues of periodontitis subjects.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global coronavirus (COVID-19) pandemic. Although initially viewed as an acute respiratory illness, COVID-19 is clearly a complex multisystemic disease with extensive cardiovascular involvement. Emerging evidence shows that the endothelium plays multiple roles in COVID-19 physiopathology, as both a target organ that can be directly infected by SARS-CoV-2 and a mediator in the subsequent inflammatory and thrombotic cascades. Arterial stiffness is an established marker of cardiovascular disease. The scope of this review is to summarize available data on the acute and long-term consequences of COVID-19 on vascular function. COVID-19 causes early vascular aging and arterial stiffness. Fast, noninvasive bedside assessment of arterial stiffness could optimize risk stratification in acute COVID-19, allowing for early escalation of treatment. Vascular physiology remains impaired at least 12 months after infection with SARS-CoV-2, even in otherwise healthy adults. This raises concerns regarding the extent of arterial remodeling in patients with preexisting vascular disease and the potential development of a persistent, chronic COVID-19 vasculopathy. Long-term follow up on larger cohorts is required to investigate the reversibility of COVID-19-induced vascular changes and their associated prognostic implications. [ABSTRACT FROM AUTHOR]

Hepatic diseases pose a significant public health concern. Regardless of the severity of hepatic fibrosis, treatment is recommended for all chronic hepatitis C virus (HCV) subjects. However, fibrosis and steatosis assessment remains crucial for evaluating the prognosis, progression, and hepatic disease monitoring, particularly following the treatment with direct-acting antivirals (DAAs). The aim of our study was to evaluate the impact of metabolic factors and the extent of hepatic fibrosis and fat accumulation in chronic HCV infection subjects. Additionally, another objective was to investigate modifications regarding fibrosis and steatosis three months after a successful sustained viral response (SVR). A total of 100 patients with compensated cirrhosis and chronic hepatitis C (CHC) were included in our study. These patients received treatment with DAA and underwent Fibromax assessment before and three months post SVR. After DAA treatment, a significant decrease was observed in the degree of hepatic fibrosis and hepatic steatosis. This regression was evident three months following the achievement of SVR. Chronic viral hepatitis C may trigger risk factors for metabolic syndromes, such as obesity and type 2 diabetes mellitus. Conclusions: It is crucial to monitor metabolic factors and take timely measures to prevent or treat metabolic syndrome in patients with chronic viral hepatitis C.

The interaction of radiation with matter takes place through energy transfer and is accomplished especially by ionized atoms or molecules. The effect of radiation on biological systems involves multiple physical, chemical and biological steps. Direct effects result in a large number of reactive oxygen species (ROS) within and outside and inside of the cells as well, which are responsible for oxidative stress. Indirect effects are defined as alteration of normal biological processes and cellular components (DNA, protein, lipids, etc.) caused by the reactive oxygen species directly induced by radiation. In this work, a classical design of an electrochemical (EC) three-electrodes system was employed for analyzing the effects of proton beam radiation on melanoma B16 cell line. In order to investigate the effect of proton radiation on the B16 cells, the cells were grown on the EC surface and irradiated. After optimization of the experimental set-up and dosimetry, the radiobiological experiments were performed at doses ranging between 0 and 2 Gy and the effect of proton beam irradiation on the cells was evaluated by the means of cyclic voltammetry and measuring the open circuit potential between working and reference electrodes. [ABSTRACT FROM AUTHOR]

The paper aims to investigate the cytotoxic effect on tumor cells of irradiated AuNPs in green light and subsequently functionalized with HS-PEG-NH2. The toxicity level of gold conjugates after their functionalization with DOX and TAT peptide was also evaluated. The AuNPs were prepared using the modified Turkevich method and exposed to visible light at a wavelength of 520 nm prior their PEGylation. The optical properties were analyzed by UV-vis spectroscopy, the surface modification was investigated using FTIR and XPS spectroscopies and their sizes and morphologies were evaluated by TEM and DLS techniques. DOX and TAT peptide were linked to the surface of PEGylated AuNPs by reacting their amino groups with glycidyloxypropyl of PEGylated DOX or TAT conjugates under mild conditions at room temperature and in the presence of ethanol as catalyst. The conjugates containing DOX or DOX and TAT have been characterized by fluorescence and FTIR techniques. The changes of electrochemical features were observed using cyclic voltammetry, suggesting a better stability of irradiated nanoparticles. By mass spectrometry it was confirmed that the compounds of interest were obtained. The cell viability test showed that irradiated and non-irradiated nanoparticles coated with PEG are not toxic in normal cells. Tumor cell viability analysis showed that the PEGylated nanoparticles modified with DOX and TAT peptide were more effective than pristine DOX, indicating cytotoxicity up to 10% higher than non-irradiated ones. [ABSTRACT FROM AUTHOR]

Background. Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care. Methods. The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions. Results. We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures. Conclusions. We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges sur [ABSTRACT FROM AUTHOR]

A magnetic bottle device with optimized sizes for high-efficiency positron moderation was manufactured and attached to a positron detection system based on two gamma detectors operating in coincidence to detect positron annihilation events. The detection system's performance was tested with a 22Na calibrated source. Titanium foils with a natural isotope mixture that were 2- μ m-thick were proton irradiated to produce 48V. Experiments with a stack of up to four 48V foils showed that the magnetic bottle trap achieved a 10-fold increase in the standard positron moderator efficiency of tungsten in transmission mode. However, the measured moderation efficiency of ∼ 0.4% was found to be in huge discrepancy with the value of 1.8% obtained by Gerchow et al. for a non-optimized trap. One possible reason for this discrepancy was pointed out, namely that Gerchow et al mainly detected moderated positrons but almost no fast/unmoderated positrons, which escape the magnetic bottle trap and should also reach the positron detector used. Our experimental and simulation results showed that the ratio of moderated to fast/unmoderated positrons that reach our detection system is about 1:7. [ABSTRACT FROM AUTHOR]

[Display omitted] • Bis(azopyrenyl) dibenzo-18-crown-6 ether system synthesis has been described. • The novel system's structure was validated by physicochemical analysis. • The excited state's photophysical properties were shown by UV-vis and fluorescence. • DFT and TD-DFT levels of theory were used to estimate the electronic configuration. • The DFT method was used to calculate and illustrate Van der Waals interactions. Understanding self-assemble process of molecules is crucial for developing synthetic analogues and improving our knowledge of natural systems. Compounds with crown-ethers and pyrene sequences in their structure have caught the attention lately due to their self-assembly abilities. A new molecular system, bis(azopyrenyl) dibenzo-18-crown-6-ether (AzoPy-18C6), was designed and obtained by sidechain modifications of both amino groups from the dibenzo-crown-ether with pyrene moieties, resulting in the formation of two azopyrene groups on each side. The compound was characterized by physico-chemical techniques such as: 1H-NMR, 13C-NMR, TGA, and DSC. Our work aimed to explore the supramolecular arrangement of the AzoPy-18C6 molecular system from a fundamental point of view based on the theoretical and experimental determinations. The Wide-Angle X-ray Diffraction (WAXD) analysis revealed a supramolecular arrangement through the appearance of a sharp peak at 2 θ = 1.914°. By investigating the photophysical properties in the excited state, by UV–vis analysis and fluorescence spectroscopy, the π-π interactions among the aromatic pyrene moieties within the ordered stacks of the AzoPy-18C6 were observed. This was confirmed also by the molecular dynamics and DFT calculations. The interplay between electronic densities of molecular orbitals was discussed in order to prove the dimer/excimer association. Theoretical calculations revealed that the dihedral angle of C-N=N-C, specific to the azopyrene units, and the Van der Waals interactions play a key role in the π-π stacking of the bis(azopyrenyl) dibenzo-18-crown-6-ether system. [ABSTRACT FROM AUTHOR]

Platelet-vessel wall interactions and local thrombosis are investigated in vivo in a branch of the mesenteric artery of the guinea pig, using optoelectronic registration and ultrastructural control. Following an electrical challenge resulting in changes of cell membrane polarization, subsequent superfusion by PAF-acether or a stable analogue, (1-O-alkyl-2-N-methylcarbamyl-sn-glycero-3-phosphocholine, 10(-8) M focal concentration (f.c.)) for a restricted period results in endothelial cell retraction and bleb formation followed by platelet adhesion and the development of a thrombus which over time becomes invaded by leukocytes and eventually occludes the vascular lumen. It was demonstrated in a previous investigation that these phenomena are triggered by the generation of endogenous PAF-acether by the endothelial cells. Specific PAF-acether-antagonists, such as BN 52021 a ginkgolide, but also synthetic molecules, derivatives of the triazolo-pyridino-diazepine group (BN 50727, BN 50755 and BN 50789), significantly inhibit platelet-vessel wall interactions and thrombosis, but not the formation of blebs in the endothelial cells. Hydrogen peroxide (10(-5)M f.c.) not only primes the effect of PAF-acether, but is by itself capable of inducing thrombosis through a PAF-acether-mediated mechanism. Inhibition of acetyl hydrolase by PMSF (phenyl-methyl-sulfonyl-fluoride, 10(-5)M f.c.) invariably results in a significant enhancement of thrombosis, while conversely, inhibition of acetyl transferase by 27584 RP (4-(naphtylvinyl)pyridine hydrochloride, 10(-6)M f.c.) inhibits thromboformation indicating that the remodeling pathway is involved.

Study Objective: The aim was to investigate the role of platelet activating factor (PAF) in myocardial ischaemia by using BN 50739, a new specific PAF receptor antagonist with a hetrazepine framework., Design: Isolated working rat hearts were subjected to regional ischaemia, induced by ligation of the left main coronary artery for 30 min, followed by reperfusion. BN 50739 was applied at concentrations of 10(-7), 10(-6), 10(-5) and 5 X 10(-5) M, and its effects on the incidence of ischaemia induced and reperfusion induced ventricular tachycardia and ventricular fibrillation and heart functions, such as heart rate, coronary flow, aortic flow, left ventricular developed pressure (LVDP), its first derivative (LVdP/dtmax), and left ventricular end diastolic pressure (LVEDP), were determined., Experimental Material: Studies were performed on isolated working hearts of male Sprague-Dawley rats weighing 300-360 g. Hearts were perfused with BN 50739 dissolved in dimethylsulphoxide. Control hearts were perfused with the vehicle., Measurements and Main Results: Regional ischaemia triggered ventricular arrhythmias showing high incidence between 12 and 20 min with peak appearance at 16 min. BN 50739 induced dose dependent protection against ventricular tachycardia and fibrillation: incidences declined from their respective control values of 91% and 75% to 33% (p less than 0.05) and 8% (p less than 0.05) after exposure to 10(-5) M, and to 25% (p less than 0.05) and 8% (p less than 0.05) after exposure to 5 X 10(-5) M concentrations. Reperfusion of the ischaemic myocardium resulted in an immediate appearance of ventricular tachycardia and fibrillation, but these were not suppressed by the PAF antagonist. Regional ischaemia slightly reduced heart rate, markedly decreased coronary flow, aortic flow, LVDP and LVdP/dtmax, and increased LVEDP. With the exception of LVEDP, these variables were not influenced by the drug. BN 50739, applied at a concentration of 5 X 10(-5) M, reduced LVEDP significantly during the whole ischaemic period., Conclusions: Under in vitro conditions PAF is likely to be involved in the genesis of ischaemia induced ventricular arrhythmias since BN 50739, a specific PAF receptor antagonist, exerts a protective effect against these rhythm disturbances. This suggests that PAF antagonists may have benefit in the clinical management of acute myocardial ischaemia.

We have studied the metabolic and functional effects of two new platelet-activating factor (PAF) antagonists (BN 50726 and BN 50739) and their diluent (dimethyl sulfoxide; DMSO) during reoxygenation of the 14-min ischemic isolated brain. Blood gases, EEG, auditory evoked potentials, cerebral metabolic rate for glucose (CMRglc), and cerebral metabolic rate for oxygen (CMRO2) were monitored throughout the study. Frozen brain samples were taken for measurement of brain tissue high-energy phosphates, carbohydrate content, and thiobarbituric acid-reactive material (TBAR, an indicator of lipid peroxidation) at the end of the study. Following 60 min of reoxygenation in the nontreated 14-min ischemic brains, lactate, AMP, creatine (Cr), intracellular hydrogen ion concentration [H+]i), and TBAR values were significantly higher and ATP, creatine phosphate (PCr), CMRglc, CMRO2, and energy charge (EC) values were significantly lower than the corresponding normoxic control values. PCr and CMRO2 values were significantly higher, and glycogen, AMP, and [H+]i values were significantly lower in the BN 50726-treated ischemic brains than in DMSO-treated ischemic brains. In brains treated with BN 50739, ATP, ADP, PCr, CMRO2, and EC values were significantly higher, and lactate, AMP, Cr, and [H+]i values were significantly lower than corresponding values in the DMSO-treated ischemic brains. TBAR values were near control levels in all brains exposed to DMSO. There was also marked recovery of EEG and auditory evoked potentials in brains treated with DMSO. Treatment with BN 50726 or BN 50739 in DMSO appeared to improve brain mitochondrial function and energy metabolism partly as the result of DMSO action as a free radical scavenger.(ABSTRACT TRUNCATED AT 250 WORDS)