Pub Date : 2024-01-14DOI: 10.3390/pathophysiology31010004
Mijo Meter, Josip Andelo Borovac
An electrical storm (ES) is defined as the presence of at least three episodes of sustained ventricular tachycardia or ventricular fibrillation within 24 h. This patient had a previously known arterial hypertension, type II diabetes mellitus, and chronic kidney disease and has presented to the Emergency Department (ED) with symptoms of retrosternal chest pain lasting for several hours prior. The initial 12-lead electrocardiogram revealed ST segment elevation in the anterior leads (V1-V6). Emergent coronary angiography revealed an acute occlusion of the proximal left anterior descending artery (pLAD) and percutaneous coronary intervention was performed with successful implantation of one drug-eluting stent in the pLAD. On day 8 of hospitalization, the patient developed a refractory ES for which he received 50 DC shocks and did not respond to multiple lines of antiarrhythmic medications. Due to a failure of medical therapy, we decided to implant a temporary pacemaker and initiate ventricular overdrive pacing (VOP) that was successful in terminating ES. Following electrical stabilization, the patient underwent a successful ICD implantation. This case demonstrates that VOP can contribute to hemodynamic and electrical stabilization of a patient that suffers from refractory ES and this treatment modality might serve as a temporary bridge to ICD implantation.
{"title":"A Refractory Electrical Storm after Acute Myocardial Infarction: The Role of Temporary Ventricular Overdrive Pacing as a Bridge to ICD Implantation.","authors":"Mijo Meter, Josip Andelo Borovac","doi":"10.3390/pathophysiology31010004","DOIUrl":"10.3390/pathophysiology31010004","url":null,"abstract":"<p><p>An electrical storm (ES) is defined as the presence of at least three episodes of sustained ventricular tachycardia or ventricular fibrillation within 24 h. This patient had a previously known arterial hypertension, type II diabetes mellitus, and chronic kidney disease and has presented to the Emergency Department (ED) with symptoms of retrosternal chest pain lasting for several hours prior. The initial 12-lead electrocardiogram revealed ST segment elevation in the anterior leads (V1-V6). Emergent coronary angiography revealed an acute occlusion of the proximal left anterior descending artery (pLAD) and percutaneous coronary intervention was performed with successful implantation of one drug-eluting stent in the pLAD. On day 8 of hospitalization, the patient developed a refractory ES for which he received 50 DC shocks and did not respond to multiple lines of antiarrhythmic medications. Due to a failure of medical therapy, we decided to implant a temporary pacemaker and initiate ventricular overdrive pacing (VOP) that was successful in terminating ES. Following electrical stabilization, the patient underwent a successful ICD implantation. This case demonstrates that VOP can contribute to hemodynamic and electrical stabilization of a patient that suffers from refractory ES and this treatment modality might serve as a temporary bridge to ICD implantation.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"31 1","pages":"44-51"},"PeriodicalIF":2.7,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10801483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-10DOI: 10.3390/pathophysiology31010003
Matthew L Repp, I. Chinyere
The use of catheter-based irreversible electroporation in clinical cardiac laboratories, termed pulsed-field ablation (PFA), is gaining international momentum among cardiac electrophysiology proceduralists for the non-thermal management of both atrial and ventricular tachyrhythmogenic substrates. One area of potential application for PFA is in the mitigation of ventricular tachycardia (VT) risk in the setting of ischemia-mediated myocardial fibrosis, as evidenced by recently published clinical case reports. The efficacy of tissue electroporation has been documented in other branches of science and medicine; however, ventricular PFA’s potential advantages and pitfalls are less understood. This comprehensive review will briefly summarize the pathophysiological mechanisms underlying VT and then summarize the pre-clinical and adult clinical data published to date on PFA’s effectiveness in treating monomorphic VT. These data will be contrasted with the effectiveness ascribed to thermal cardiac ablation modalities to treat VT, namely radiofrequency energy and liquid nitrogen-based cryoablation.
{"title":"Opportunities and Challenges in Catheter-Based Irreversible Electroporation for Ventricular Tachycardia","authors":"Matthew L Repp, I. Chinyere","doi":"10.3390/pathophysiology31010003","DOIUrl":"https://doi.org/10.3390/pathophysiology31010003","url":null,"abstract":"The use of catheter-based irreversible electroporation in clinical cardiac laboratories, termed pulsed-field ablation (PFA), is gaining international momentum among cardiac electrophysiology proceduralists for the non-thermal management of both atrial and ventricular tachyrhythmogenic substrates. One area of potential application for PFA is in the mitigation of ventricular tachycardia (VT) risk in the setting of ischemia-mediated myocardial fibrosis, as evidenced by recently published clinical case reports. The efficacy of tissue electroporation has been documented in other branches of science and medicine; however, ventricular PFA’s potential advantages and pitfalls are less understood. This comprehensive review will briefly summarize the pathophysiological mechanisms underlying VT and then summarize the pre-clinical and adult clinical data published to date on PFA’s effectiveness in treating monomorphic VT. These data will be contrasted with the effectiveness ascribed to thermal cardiac ablation modalities to treat VT, namely radiofrequency energy and liquid nitrogen-based cryoablation.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"5 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139439214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-09DOI: 10.3390/pathophysiology31010002
L. Santacroce, S. Topi, I. Charitos, R. Lovero, Paolo Luperto, Raffele Palmirotta, Emilio Jirillo
Superantigens, i.e., staphylococcal enterotoxins and toxic shock syndrome toxin-1, interact with T cells in a different manner in comparison to conventional antigens. In fact, they activate a larger contingent of T lymphocytes, binding outside the peptide-binding groove of the major histocompatibility complex class II. Involvement of many T cells by superantigens leads to a massive release of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor-alpha and interferon-gamma. Such a storm of mediators has been shown to account for tissue damage, multiorgan failure and shock. Besides conventional drugs and biotherapeutics, experiments with natural and biological products have been undertaken to attenuate the toxic effects exerted by superantigens. In this review, emphasis will be placed on polyphenols, probiotics, beta-glucans and antimicrobial peptides. In fact, these substances share a common functional denominator, since they skew the immune response toward an anti-inflammatory profile, thus mitigating the cytokine wave evoked by superantigens. However, clinical applications of these products are still scarce, and more trials are needed to validate their usefulness in humans.
超级抗原,即葡萄球菌肠毒素和中毒性休克综合症毒素-1,与传统抗原相比,以不同的方式与 T 细胞相互作用。事实上,它们能激活更多的 T 淋巴细胞,在主要组织相容性复合体 II 类的肽结合槽外结合。超级抗原使许多 T 细胞参与其中,导致大量释放促炎细胞因子,如白细胞介素(IL)-1、IL-2、IL-6、肿瘤坏死因子-α 和干扰素-γ。这种介质风暴已被证明是造成组织损伤、多器官衰竭和休克的原因。除了传统药物和生物疗法外,人们还利用天然产品和生物制品进行实验,以减轻超抗原产生的毒性效应。在本综述中,重点将放在多酚、益生菌、β-葡聚糖和抗菌肽上。事实上,这些物质都有一个共同的功能特点,即它们能使免疫反应偏向于抗炎,从而减轻超级抗原引起的细胞因子波。然而,这些产品的临床应用仍然很少,需要更多的试验来验证它们在人体中的效用。
{"title":"Current Views about the Inflammatory Damage Triggered by Bacterial Superantigens and Experimental Attempts to Neutralize Superantigen-Mediated Toxic Effects with Natural and Biological Products","authors":"L. Santacroce, S. Topi, I. Charitos, R. Lovero, Paolo Luperto, Raffele Palmirotta, Emilio Jirillo","doi":"10.3390/pathophysiology31010002","DOIUrl":"https://doi.org/10.3390/pathophysiology31010002","url":null,"abstract":"Superantigens, i.e., staphylococcal enterotoxins and toxic shock syndrome toxin-1, interact with T cells in a different manner in comparison to conventional antigens. In fact, they activate a larger contingent of T lymphocytes, binding outside the peptide-binding groove of the major histocompatibility complex class II. Involvement of many T cells by superantigens leads to a massive release of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor-alpha and interferon-gamma. Such a storm of mediators has been shown to account for tissue damage, multiorgan failure and shock. Besides conventional drugs and biotherapeutics, experiments with natural and biological products have been undertaken to attenuate the toxic effects exerted by superantigens. In this review, emphasis will be placed on polyphenols, probiotics, beta-glucans and antimicrobial peptides. In fact, these substances share a common functional denominator, since they skew the immune response toward an anti-inflammatory profile, thus mitigating the cytokine wave evoked by superantigens. However, clinical applications of these products are still scarce, and more trials are needed to validate their usefulness in humans.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"76 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139444443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-05DOI: 10.3390/pathophysiology31010001
V. Ryabkova, Artemiy V. Rubinskiy, Valeriy N. Marchenko, Vasiliy I. Trofimov, L. Churilov
Background: There is a considerable overlap between the clinical presentation of post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many of their common symptoms can be linked to dysregulation of the autonomic nervous system (dysautonomia). This study aimed to objectively assess autonomic function in a general group of patients with PCC and in a group of patients with ME/CFS whose disease was not related to COVID-19. We hypothesize that the similarity in the chronic symptoms of patients with PCC and ME/CFS extends to objective autonomic nervous system abnormalities. Methods: Synchronous recordings of an electrocardiogram and continuous dynamics of blood pressure in the digital artery using the Penaz method were obtained using the spiroarteriocardiorhythmography method in 34 patients diagnosed with ME/CFS, in whom the onset of the disease was not associated with COVID-19, 29 patients meeting the PCC definition and 32 healthy controls. Heart rate variability (HRV) and systolic and diastolic blood pressure variability (BPV) were assessed at rest and in tests with fixed respiratory rates. Indicators of baroreflex regulation (baroreflex effectiveness index and baroreflex sensitivity) were additionally determined at rest. Results: The total power and power of low-frequency and high-frequency of RR interval variability at rest as well as baroreflex sensitivity were significantly lower both in PCC and ME/CFS patients compared to healthy controls. Several diagnostic prediction models for ME/CFS were developed based on HRV parameters. During slow breathing, the HRV parameters returned to normal in PCC but not in ME/CFS patients. The correlation analysis revealed a close relationship of HRV, BPV parameters and baroreflex sensitivity with fatigue, but not with HADS depressive/anxiety symptoms in the ME/CFS and PCC patients. Conclusions: A similar pattern of HRV and baroreflex failure with signs of a pathological acceleration of age-dependent dysautonomia was identified in the ME/CFS and PCC patients. The clinical, diagnostic and therapeutic implications of these findings are discussed, in light of previously described relationships between inflammation, vascular pathology, atherosclerotic cardiovascular disease and autonomic dysfunction.
{"title":"Similar Patterns of Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue and Post-COVID-19 Syndromes","authors":"V. Ryabkova, Artemiy V. Rubinskiy, Valeriy N. Marchenko, Vasiliy I. Trofimov, L. Churilov","doi":"10.3390/pathophysiology31010001","DOIUrl":"https://doi.org/10.3390/pathophysiology31010001","url":null,"abstract":"Background: There is a considerable overlap between the clinical presentation of post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many of their common symptoms can be linked to dysregulation of the autonomic nervous system (dysautonomia). This study aimed to objectively assess autonomic function in a general group of patients with PCC and in a group of patients with ME/CFS whose disease was not related to COVID-19. We hypothesize that the similarity in the chronic symptoms of patients with PCC and ME/CFS extends to objective autonomic nervous system abnormalities. Methods: Synchronous recordings of an electrocardiogram and continuous dynamics of blood pressure in the digital artery using the Penaz method were obtained using the spiroarteriocardiorhythmography method in 34 patients diagnosed with ME/CFS, in whom the onset of the disease was not associated with COVID-19, 29 patients meeting the PCC definition and 32 healthy controls. Heart rate variability (HRV) and systolic and diastolic blood pressure variability (BPV) were assessed at rest and in tests with fixed respiratory rates. Indicators of baroreflex regulation (baroreflex effectiveness index and baroreflex sensitivity) were additionally determined at rest. Results: The total power and power of low-frequency and high-frequency of RR interval variability at rest as well as baroreflex sensitivity were significantly lower both in PCC and ME/CFS patients compared to healthy controls. Several diagnostic prediction models for ME/CFS were developed based on HRV parameters. During slow breathing, the HRV parameters returned to normal in PCC but not in ME/CFS patients. The correlation analysis revealed a close relationship of HRV, BPV parameters and baroreflex sensitivity with fatigue, but not with HADS depressive/anxiety symptoms in the ME/CFS and PCC patients. Conclusions: A similar pattern of HRV and baroreflex failure with signs of a pathological acceleration of age-dependent dysautonomia was identified in the ME/CFS and PCC patients. The clinical, diagnostic and therapeutic implications of these findings are discussed, in light of previously described relationships between inflammation, vascular pathology, atherosclerotic cardiovascular disease and autonomic dysfunction.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"7 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139381144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-18DOI: 10.3390/pathophysiology30040046
Elena Zelikovna Golukhova, Inessa Viktorovna Slivneva, Olga Sergeevna Kozlova, Bektur Shukurbekovich Berdibekov, Ivan Ivanovich Skopin, Vadim Yuryevich Merzlyakov, Renat Kamilyevich Baichurin, Igor Yuryevich Sigaev, Milena Abrekovna Keren, Mikhail Durmishkhanovich Alshibaya, Damir Ildarovich Marapov, Milena Artemovna Arzumanyan
In this meta-analysis, we examine the advantages of invasive strategies for patients diagnosed with chronic coronary heart disease (CHD) and preserved left ventricular (LV) function, as well as those with significant LV systolic dysfunction (LV ejection fraction (EF) < 45%).
Material and methods: We conducted a systematic search to identify all randomized trials directly comparing invasive strategies with optimal medical therapy (OMT) in patients diagnosed with chronic CHD. Data from these trials were pooled using a random-effects meta-analysis. The primary outcome assessed was the all-cause mortality, while secondary endpoints included cardiovascular (CV) death, stroke, myocardial infarction (MI), and unplanned revascularization. This study was designed to assess the benefits of both invasive strategies and OMT in patients with preserved LV function and in those with LV systolic dysfunction. The statistical analysis of the data was conducted using the Review Manager (RevMan) software, version 5.4.1 (The Cochrane Collaboration, 2020).
Results: Twelve randomized studies enrolling 13,912 patients were included in the final analysis. Among the patients with chronic CHD and preserved LV systolic function, revascularization did not demonstrate a reduction in all-cause mortality (8.52% vs. 8.45%, p = 0.45), CV death (3.41% vs. 3.62%, p = 0.08), or the incidence of MI (9.88% vs. 10.49%, p = 0.47). However, the need for unplanned myocardial revascularization was significantly lower in the group following the initial invasive approach compared to patients undergoing OMT (14.75% vs. 25.72%, p < 0.001). In contrast, the invasive strategy emerged as the preferred treatment modality for patients with ischemic LV systolic dysfunction. This approach demonstrated lower rates of all-cause mortality (40.61% vs. 46.52%, p = 0.004), CV death (28.75% vs. 35.82%, p = 0.0004), and MI (8.19% vs. 10.8%, p = 0.03).
Conclusions: In individuals diagnosed with chronic CHD and preserved LV EF, the initial invasive approach did not demonstrate a clinical advantage over OMT. Conversely, in patients with ischemic LV systolic dysfunction, myocardial revascularization was found to reduce the risks of CV events and enhance the overall outcomes. These findings hold significant clinical relevance for optimizing treatment strategies in patients with chronic CHD, contingent upon myocardial contractility status.
在这项荟萃分析中,我们研究了对确诊为慢性冠心病(CHD)且左心室(LV)功能保留的患者以及左心室收缩功能明显障碍(LV射血分数(EF)<45%)的患者采用侵入性策略的优势:我们进行了一次系统性检索,以确定所有直接比较慢性冠心病患者的侵入性策略与最佳药物治疗(OMT)的随机试验。我们采用随机效应荟萃分析法对这些试验的数据进行了汇总。评估的主要结果是全因死亡率,次要终点包括心血管(CV)死亡、中风、心肌梗死(MI)和意外血管再通。该研究旨在评估有创策略和 OMT 对左心室功能保留患者和左心室收缩功能障碍患者的益处。研究数据的统计分析采用了5.4.1版的Review Manager(RevMan)软件(Cochrane Collaboration,2020年):最终分析纳入了 12 项随机研究,共 13,912 例患者。在患有慢性冠心病且左心室收缩功能保留的患者中,血管重建并不能降低全因死亡率(8.52% vs. 8.45%,P = 0.45)、冠心病死亡(3.41% vs. 3.62%,P = 0.08)或心肌梗死发生率(9.88% vs. 10.49%,P = 0.47)。然而,与接受 OMT 的患者相比,采用初始有创方法的患者组对计划外心肌血运重建的需求明显降低(14.75% 对 25.72%,p < 0.001)。相比之下,有创策略成为缺血性左心室收缩功能障碍患者的首选治疗方式。这种方法的全因死亡率(40.61% vs. 46.52%,P = 0.004)、心血管疾病死亡率(28.75% vs. 35.82%,P = 0.0004)和心肌梗死率(8.19% vs. 10.8%,P = 0.03)均较低:对于确诊为慢性冠心病且左心室EF值保留的患者,最初的侵入性方法与OMT相比并不具有临床优势。相反,在缺血性左心室收缩功能障碍患者中,心肌血运重建可降低发生心血管事件的风险,提高总体疗效。这些研究结果对优化慢性冠心病患者的治疗策略具有重要的临床意义,这取决于心肌收缩力状态。
{"title":"Treatment Strategies for Chronic Coronary Heart Disease with Left Ventricular Systolic Dysfunction or Preserved Ejection Fraction-A Systematic Review and Meta-Analysis.","authors":"Elena Zelikovna Golukhova, Inessa Viktorovna Slivneva, Olga Sergeevna Kozlova, Bektur Shukurbekovich Berdibekov, Ivan Ivanovich Skopin, Vadim Yuryevich Merzlyakov, Renat Kamilyevich Baichurin, Igor Yuryevich Sigaev, Milena Abrekovna Keren, Mikhail Durmishkhanovich Alshibaya, Damir Ildarovich Marapov, Milena Artemovna Arzumanyan","doi":"10.3390/pathophysiology30040046","DOIUrl":"10.3390/pathophysiology30040046","url":null,"abstract":"<p><p>In this meta-analysis, we examine the advantages of invasive strategies for patients diagnosed with chronic coronary heart disease (CHD) and preserved left ventricular (LV) function, as well as those with significant LV systolic dysfunction (LV ejection fraction (EF) < 45%).</p><p><strong>Material and methods: </strong>We conducted a systematic search to identify all randomized trials directly comparing invasive strategies with optimal medical therapy (OMT) in patients diagnosed with chronic CHD. Data from these trials were pooled using a random-effects meta-analysis. The primary outcome assessed was the all-cause mortality, while secondary endpoints included cardiovascular (CV) death, stroke, myocardial infarction (MI), and unplanned revascularization. This study was designed to assess the benefits of both invasive strategies and OMT in patients with preserved LV function and in those with LV systolic dysfunction. The statistical analysis of the data was conducted using the Review Manager (RevMan) software, version 5.4.1 (The Cochrane Collaboration, 2020).</p><p><strong>Results: </strong>Twelve randomized studies enrolling 13,912 patients were included in the final analysis. Among the patients with chronic CHD and preserved LV systolic function, revascularization did not demonstrate a reduction in all-cause mortality (8.52% vs. 8.45%, <i>p</i> = 0.45), CV death (3.41% vs. 3.62%, <i>p</i> = 0.08), or the incidence of MI (9.88% vs. 10.49%, <i>p</i> = 0.47). However, the need for unplanned myocardial revascularization was significantly lower in the group following the initial invasive approach compared to patients undergoing OMT (14.75% vs. 25.72%, <i>p</i> < 0.001). In contrast, the invasive strategy emerged as the preferred treatment modality for patients with ischemic LV systolic dysfunction. This approach demonstrated lower rates of all-cause mortality (40.61% vs. 46.52%, <i>p</i> = 0.004), CV death (28.75% vs. 35.82%, <i>p</i> = 0.0004), and MI (8.19% vs. 10.8%, <i>p</i> = 0.03).</p><p><strong>Conclusions: </strong>In individuals diagnosed with chronic CHD and preserved LV EF, the initial invasive approach did not demonstrate a clinical advantage over OMT. Conversely, in patients with ischemic LV systolic dysfunction, myocardial revascularization was found to reduce the risks of CV events and enhance the overall outcomes. These findings hold significant clinical relevance for optimizing treatment strategies in patients with chronic CHD, contingent upon myocardial contractility status.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 4","pages":"640-658"},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10747738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-05DOI: 10.3390/pathophysiology30040045
Thiago Guedes Pinto, M. Viana, Patricia Ramos Cury, M. D. Martins, Jean Nunes dos Santos, Daniel Araki Ribeiro
The aim of this systematic review was to answer the question of whether crack cocaine can induce cellular and molecular alterations and whether such alterations are somehow related to clinical lesions in the oral mucosa. The searches were undertaken in three electronic databases and conducted based on the PRISMA 2020 statement. Eleven studies published between 1994 and 2020 were analyzed. The quality of the included studies was assessed by two independent reviewers (TGP and DAR) through a confounder’s categorization methodology, in which final ratings were attributed (strong, moderate or weak) for each study. From 11 studies included, 7 evaluated the cellular/molecular impact of the addiction in a total of 492 individuals and compared to a control (non-exposure) group (n = 472). The main tests used for cellular alteration were MN and AgNORs. Cells from crack cocaine groups exhibited increased proliferation and MN counting. Only four studies evaluated the prevalence of oral lesions. All of them showed that individuals exposed to crack cocaine presented an increased number of oral lesions. Most studies showed good quality. In conclusion, our results demonstrate that crack use may induce changes at the cellular and molecular level and also exhibit an increased number of oral lesions. However, a correlation between such changes and oral mucosa lesions still needs further investigation and elucidation through other clinical studies in humans.
{"title":"Are Cytomorphogenetic Events Correlated with Oral Mucosal Lesions Induced by Crack Cocaine Use? A Systematic Review","authors":"Thiago Guedes Pinto, M. Viana, Patricia Ramos Cury, M. D. Martins, Jean Nunes dos Santos, Daniel Araki Ribeiro","doi":"10.3390/pathophysiology30040045","DOIUrl":"https://doi.org/10.3390/pathophysiology30040045","url":null,"abstract":"The aim of this systematic review was to answer the question of whether crack cocaine can induce cellular and molecular alterations and whether such alterations are somehow related to clinical lesions in the oral mucosa. The searches were undertaken in three electronic databases and conducted based on the PRISMA 2020 statement. Eleven studies published between 1994 and 2020 were analyzed. The quality of the included studies was assessed by two independent reviewers (TGP and DAR) through a confounder’s categorization methodology, in which final ratings were attributed (strong, moderate or weak) for each study. From 11 studies included, 7 evaluated the cellular/molecular impact of the addiction in a total of 492 individuals and compared to a control (non-exposure) group (n = 472). The main tests used for cellular alteration were MN and AgNORs. Cells from crack cocaine groups exhibited increased proliferation and MN counting. Only four studies evaluated the prevalence of oral lesions. All of them showed that individuals exposed to crack cocaine presented an increased number of oral lesions. Most studies showed good quality. In conclusion, our results demonstrate that crack use may induce changes at the cellular and molecular level and also exhibit an increased number of oral lesions. However, a correlation between such changes and oral mucosa lesions still needs further investigation and elucidation through other clinical studies in humans.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"132 29","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138598979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-04DOI: 10.3390/pathophysiology30040044
Hannah R. Popper, Brian E. Fliegel, Dawn M. Elliott, Alvin W. Su
The menisci increase the contact area of load bearing in the knee and thus disperse the mechanical stress via their circumferential tensile fibers. Traumatic meniscus injuries cause mechanical symptoms in the knee, and are more prevalent amongst younger, more active patients, compared to degenerative tears amongst the elderly population. Traumatic meniscus tears typically result from the load-and-shear mechanism in the knee joint. The treatment depends on the size, location, and pattern of the tear. For non-repairable tears, partial or total meniscal resection decreases its tensile stress and increases joint contact stress, thus potentiating the risk of arthritis. A longitudinal vertical tear pattern at the peripheral third red-red zone leads to higher healing potential after repair. The postoperative rehabilitation protocols after repair range from immediate weight-bearing with no range of motion restrictions to non-weight bearing and delayed mobilization for weeks. Pediatric and adolescent patients may require special considerations due to their activity levels, or distinct pathologies such as a discoid meniscus. Further biomechanical and biologic evidence is needed to guide surgical management, postoperative rehabilitation protocols, and future technology applications for traumatic meniscus injuries.
{"title":"Surgical Management of Traumatic Meniscus Injuries","authors":"Hannah R. Popper, Brian E. Fliegel, Dawn M. Elliott, Alvin W. Su","doi":"10.3390/pathophysiology30040044","DOIUrl":"https://doi.org/10.3390/pathophysiology30040044","url":null,"abstract":"The menisci increase the contact area of load bearing in the knee and thus disperse the mechanical stress via their circumferential tensile fibers. Traumatic meniscus injuries cause mechanical symptoms in the knee, and are more prevalent amongst younger, more active patients, compared to degenerative tears amongst the elderly population. Traumatic meniscus tears typically result from the load-and-shear mechanism in the knee joint. The treatment depends on the size, location, and pattern of the tear. For non-repairable tears, partial or total meniscal resection decreases its tensile stress and increases joint contact stress, thus potentiating the risk of arthritis. A longitudinal vertical tear pattern at the peripheral third red-red zone leads to higher healing potential after repair. The postoperative rehabilitation protocols after repair range from immediate weight-bearing with no range of motion restrictions to non-weight bearing and delayed mobilization for weeks. Pediatric and adolescent patients may require special considerations due to their activity levels, or distinct pathologies such as a discoid meniscus. Further biomechanical and biologic evidence is needed to guide surgical management, postoperative rehabilitation protocols, and future technology applications for traumatic meniscus injuries.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"20 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138603682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-02DOI: 10.3390/pathophysiology30040043
Masatoshi Hayashi
The pathophysiology of myasthenia gravis (MG) has been largely elucidated over the past half century, and treatment methods have advanced. However, the number of cases of childhood-onset MG is smaller than that of adult MG, and the treatment of childhood-onset MG has continued to be based on research in the adult field. Research on pathophysiology and treatment methods that account for the unique growth and development of children is now desired. According to an epidemiological survey conducted by the Ministry of Health, Labour and Welfare of Japan, the number of patients with MG by age of onset in Japan is high in early childhood. In recent years, MG has been reported from many countries around the world, but the pattern of the number of patients by age of onset differs between East Asia and Western Europe, confirming that the Japanese pattern is common in East Asia. Furthermore, there are racial differences in autoimmune MG and congenital myasthenic syndromes according to immunogenetic background, and their pathophysiology and relationships are gradually becoming clear. In addition, treatment options are also recognized in different regions of the world. In this review article, I will present recent findings focusing on the differences in pathophysiology.
{"title":"Pathophysiology of Childhood-Onset Myasthenia: Abnormalities of Neuromuscular Junction and Autoimmunity and Its Background","authors":"Masatoshi Hayashi","doi":"10.3390/pathophysiology30040043","DOIUrl":"https://doi.org/10.3390/pathophysiology30040043","url":null,"abstract":"The pathophysiology of myasthenia gravis (MG) has been largely elucidated over the past half century, and treatment methods have advanced. However, the number of cases of childhood-onset MG is smaller than that of adult MG, and the treatment of childhood-onset MG has continued to be based on research in the adult field. Research on pathophysiology and treatment methods that account for the unique growth and development of children is now desired. According to an epidemiological survey conducted by the Ministry of Health, Labour and Welfare of Japan, the number of patients with MG by age of onset in Japan is high in early childhood. In recent years, MG has been reported from many countries around the world, but the pattern of the number of patients by age of onset differs between East Asia and Western Europe, confirming that the Japanese pattern is common in East Asia. Furthermore, there are racial differences in autoimmune MG and congenital myasthenic syndromes according to immunogenetic background, and their pathophysiology and relationships are gradually becoming clear. In addition, treatment options are also recognized in different regions of the world. In this review article, I will present recent findings focusing on the differences in pathophysiology.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"111 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138607653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.3390/pathophysiology30040042
N. Gogiberidze, A. Suvorov, Elizaveta Sultygova, Z. Sagirova, N. Kuznetsova, D. Gognieva, Petr Chomakhidze, Victor Frolov, Aleksandra Bykova, Dinara Mesitskaya, Alena Novikova, Danila Kondakov, Alexey Volovchenko, Stefano Omboni, P. Kopylov
It would be useful to develop a reliable method for the cuffless measurement of blood pressure (BP), as such a method could be made available anytime and anywhere for the effective screening and monitoring of arterial hypertension. The purpose of this study is to evaluate blood pressure measurements through a CardioQVARK device in clinical practice in different patient groups. Methods: This study involved 167 patients aged 31 to 88 years (mean 64.2 ± 7.8 years) with normal blood pressure, high blood pressure, and compensated high blood pressure. During each session, three routine blood pressure measurements with intervals of 30 s were taken using a sphygmomanometer with an appropriate cuff size, and the mean value was selected for comparison. The measurements were carried out by two observers trained at the same time with a reference sphygmomanometer using a Y-shaped connector. In the minute following the last cuff-based measurements, an electrocardiogram (ECG) with an I-lead and a photoplethysmocardiogram were recorded simultaneously for 3 min with the CardioQVARK device. We compared the systolic and diastolic BP obtained from a cuff-based mercury sphygmomanometer and smartphone-case-based BP device: the CardioQVARK monitor. A statistical analysis plan was developed using the IEEE Standard for Wearable Cuffless Blood Pressure Devices. Bland–Altman plots were used to estimate the precision of cuffless measurements. Results: The mean difference between the values defined by CardioQVARK and the cuff-based sphygmomanometer for systolic blood pressure (SBP) was 0.31 ± 3.61, while that for diastolic blood pressure (DBP) was 0.44 ± 3.76. The mean absolute difference (MAD) for SBP was 3.44 ± 2.5 mm Hg, and that for DBP was 3.21 ± 2.82 mm Hg. In the subgroups, the smallest error (less than 3 mm Hg) was observed in the prehypertension group, with a slightly larger error (up to 4 mm Hg) found among patients with a normal blood pressure and stage 1 hypertension. The largest error was found in the stage 2 hypertension group (4–5.5 mm Hg). The largest error was 4.2 mm Hg in the high blood pressure group. We, therefore, did not record an error in excess of 7 mmHg, the upper boundary considered acceptable in the IEEE recommendations. We also did not reach a mean error of 5 mmHg, the upper boundary considered acceptable according to the very recent ESH recommendations. At the same time, in all groups of patients, the systolic blood pressure was determined with an error of less than 5 mm Hg in more than 80% of patients. While this study shows that the CardioQVARK device meets the standards of IEEE, the Bland–Altman analysis indicates that the cuffless measurement of diastolic blood pressure has significant bias. The difference was very small and unlikely to be of clinical relevance for the individual patient, but it may well have epidemiological relevance on a population level. Therefore, the CardioQVARK device, while being worthwhile for monitoring patients over
开发一种可靠的无袖套血压测量方法,可以随时随地对高血压进行有效的筛查和监测。本研究的目的是通过CardioQVARK设备在不同患者组的临床实践中评估血压测量。方法:167例血压正常、高血压和代偿性高血压患者,年龄31 ~ 88岁(平均64.2±7.8岁)。在每个疗程中,使用适当袖带尺寸的血压计进行3次常规血压测量,间隔30 s,并选择平均值进行比较。测量由两名同时训练的观测者进行,他们使用使用y形接头的参考血压计。在最后一次袖带测量后的一分钟内,使用CardioQVARK设备同时记录心电图(ECG)(含i导联)和光电容积描记图3分钟。我们比较了基于袖带的水银血压计和基于智能手机盒的血压设备CardioQVARK监测仪获得的收缩压和舒张压。使用IEEE可穿戴式无袖带血压仪标准制定了统计分析计划。Bland-Altman图用于估计无断口测量的精度。结果:CardioQVARK与袖带式血压计测定的收缩压(SBP)均值差为0.31±3.61,舒张压(DBP)均值差为0.44±3.76。收缩压的平均绝对差(MAD)为3.44±2.5 mm Hg,舒张压的平均绝对差(MAD)为3.21±2.82 mm Hg。在亚组中,高血压前期组的误差最小(小于3 mm Hg),血压正常和1期高血压患者的误差略大(高达4 mm Hg)。误差最大的是2期高血压组(4-5.5 mm Hg)。高血压组最大误差为4.2 mm Hg。因此,我们没有记录到超过7毫米汞柱的误差,这是IEEE建议中可接受的上限。我们也没有达到5毫米汞柱的平均误差,根据最近的ESH建议,这是可接受的上限。同时,在所有患者组中,超过80%的患者的收缩压测定误差小于5 mm Hg。虽然本研究表明CardioQVARK设备符合IEEE标准,但Bland-Altman分析表明,无袖带舒张压测量存在显著偏差。这种差异非常小,不太可能与个别患者的临床相关,但在人群水平上很可能具有流行病学相关性。因此,CardioQVARK设备虽然值得长期监测患者,但可能不适合用于筛查目的。无袖带血压测量装置正在成为一种方便和可容忍的替代袖带设备。然而,需要考虑的是,无袖带血压测量设备存在一些局限性。例如,该研究显示,测量误差<5 mmHg的测量比例很高,而舒张压测量的偏差很小,尽管有统计学意义。这表明该设备可能不适合用于筛查目的。然而,其监测血压随时间变化的价值已得到证实。此外,最重要的是,简便的测量方法和设备的便携性(集成在智能手机中)可能会提高高血压患者的自我意识,并有可能提高他们对治疗的依从性。结论:本研究开发的无袖带血压技术按照IEEE协议进行了测试,在不同血压范围的患者组中具有很高的精确度。因此,该方法具有应用于临床实践的潜力。
{"title":"Practical Application of a New Cuffless Blood Pressure Measurement Method","authors":"N. Gogiberidze, A. Suvorov, Elizaveta Sultygova, Z. Sagirova, N. Kuznetsova, D. Gognieva, Petr Chomakhidze, Victor Frolov, Aleksandra Bykova, Dinara Mesitskaya, Alena Novikova, Danila Kondakov, Alexey Volovchenko, Stefano Omboni, P. Kopylov","doi":"10.3390/pathophysiology30040042","DOIUrl":"https://doi.org/10.3390/pathophysiology30040042","url":null,"abstract":"It would be useful to develop a reliable method for the cuffless measurement of blood pressure (BP), as such a method could be made available anytime and anywhere for the effective screening and monitoring of arterial hypertension. The purpose of this study is to evaluate blood pressure measurements through a CardioQVARK device in clinical practice in different patient groups. Methods: This study involved 167 patients aged 31 to 88 years (mean 64.2 ± 7.8 years) with normal blood pressure, high blood pressure, and compensated high blood pressure. During each session, three routine blood pressure measurements with intervals of 30 s were taken using a sphygmomanometer with an appropriate cuff size, and the mean value was selected for comparison. The measurements were carried out by two observers trained at the same time with a reference sphygmomanometer using a Y-shaped connector. In the minute following the last cuff-based measurements, an electrocardiogram (ECG) with an I-lead and a photoplethysmocardiogram were recorded simultaneously for 3 min with the CardioQVARK device. We compared the systolic and diastolic BP obtained from a cuff-based mercury sphygmomanometer and smartphone-case-based BP device: the CardioQVARK monitor. A statistical analysis plan was developed using the IEEE Standard for Wearable Cuffless Blood Pressure Devices. Bland–Altman plots were used to estimate the precision of cuffless measurements. Results: The mean difference between the values defined by CardioQVARK and the cuff-based sphygmomanometer for systolic blood pressure (SBP) was 0.31 ± 3.61, while that for diastolic blood pressure (DBP) was 0.44 ± 3.76. The mean absolute difference (MAD) for SBP was 3.44 ± 2.5 mm Hg, and that for DBP was 3.21 ± 2.82 mm Hg. In the subgroups, the smallest error (less than 3 mm Hg) was observed in the prehypertension group, with a slightly larger error (up to 4 mm Hg) found among patients with a normal blood pressure and stage 1 hypertension. The largest error was found in the stage 2 hypertension group (4–5.5 mm Hg). The largest error was 4.2 mm Hg in the high blood pressure group. We, therefore, did not record an error in excess of 7 mmHg, the upper boundary considered acceptable in the IEEE recommendations. We also did not reach a mean error of 5 mmHg, the upper boundary considered acceptable according to the very recent ESH recommendations. At the same time, in all groups of patients, the systolic blood pressure was determined with an error of less than 5 mm Hg in more than 80% of patients. While this study shows that the CardioQVARK device meets the standards of IEEE, the Bland–Altman analysis indicates that the cuffless measurement of diastolic blood pressure has significant bias. The difference was very small and unlikely to be of clinical relevance for the individual patient, but it may well have epidemiological relevance on a population level. Therefore, the CardioQVARK device, while being worthwhile for monitoring patients over","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":" 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138616698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-30DOI: 10.3390/pathophysiology30040041
Magdy Y Elsaeed, Osama Mahmoud Mehanna, Ezz-Eldin E Abd-Allah, Mohamed Gaber Hassan, Walid Mostafa Said Ahmed, Abd El Ghany A Moustafa, Gaber E Eldesoky, Amal M Hammad, Usama Bahgat Elgazzar, Mohamed R Elnady, Fatma M Abd-Allah, Walaa M Shipl, Amr Mohamed Younes, Mostafa Rizk Magar, Ahmed E Amer, Mohamed Ali Mahmoud Abbas, Khaled Saleh Ali Elhamaky, Mohammed Hussien Mohammed Hassan
Background: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection.
Material and methods: This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats.
Results: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone.
Conclusions: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.
{"title":"Combination Therapy with Enalapril and Paricalcitol Ameliorates Streptozotocin Diabetes-Induced Testicular Dysfunction in Rats via Mitigation of Inflammation, Apoptosis, and Oxidative Stress.","authors":"Magdy Y Elsaeed, Osama Mahmoud Mehanna, Ezz-Eldin E Abd-Allah, Mohamed Gaber Hassan, Walid Mostafa Said Ahmed, Abd El Ghany A Moustafa, Gaber E Eldesoky, Amal M Hammad, Usama Bahgat Elgazzar, Mohamed R Elnady, Fatma M Abd-Allah, Walaa M Shipl, Amr Mohamed Younes, Mostafa Rizk Magar, Ahmed E Amer, Mohamed Ali Mahmoud Abbas, Khaled Saleh Ali Elhamaky, Mohammed Hussien Mohammed Hassan","doi":"10.3390/pathophysiology30040041","DOIUrl":"10.3390/pathophysiology30040041","url":null,"abstract":"<p><strong>Background: </strong>As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection.</p><p><strong>Material and methods: </strong>This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats.</p><p><strong>Results: </strong>As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone.</p><p><strong>Conclusions: </strong>Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 4","pages":"567-585"},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10747062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}