Endothelial dysfunction and risk factors for atherosclerosis in psoriatic arthritis: overview and comparison with rheumatoid arthritis.

Endothelial dysfunction (ED) is defined as an impairment in the vasodilatory, anti-thrombotic, and anti-inflammatory properties of the cells that make up the lining of blood vessels. ED is considered a key step in the development of atherosclerotic cardiovascular disease. The association between ED and systemic inflammatory diseases is well established. However, the prevalence and clinical significance of ED in psoriatic arthritis (PsA) have been investigated to a lesser extent. This review aims to explore the link between ED and PsA, including ED in macro- and microcirculation, as well as risk factors for its occurrence in PsA and its relationship with atherosclerosis in PsA. Furthermore, the ED in PsA was compared with that of rheumatoid arthritis (RA). Regarding ED in the microcirculation, the coronary flow reserve was found to be significantly reduced in individuals with PsA. The relationship between PsA and macrovascular ED is more pronounced, along with more advanced atherosclerosis detected in patients with PsA. These results are consistent with those obtained in RA studies. On the other hand, arterial stiffness and signs of vascular remodeling were found more frequently in RA than in PsA, with the potential role of efficient anti-TNF treatment in patients with PsA and psoriasis explaining this finding. The impact of ED on cardiovascular diseases and the burden of this risk caused independently by PsA have not yet been precisely established, however, this group of patients requires special attention with regard to cardiovascular events.

Current challenges in diagnosing and treating infectious skin diseases - a case series. / Choroby zakazne skóry jako wciaz aktualny problem diagnostyczny i terapeutyczny ­ przeglad nietypowych przypadków klinicznych.

Infectious skin diseases constitute a significant public health problem. Despite the systematic development of many modern diagnostic and therapeutic tools, they still pose a serious challenge for clinicians. Due to their prevalence and mild course in most cases, they are often marginalized, which can delay their diagnosis and treatment initiation. Such an approach in more clinically advanced cases can have serious consequences, sometimes leading to tragic outcomes. This work presents a series of four cases of common infectious skin diseases with an unusually atypical clinical picture: the history of a 49-year-old female patient with recurrent erysipelas of the right lower leg co-occurring with a SARS-CoV-2 infection, a 75-year-old male patient with a generalized form of herpes zoster, a 38-year-old female patient with a complicated severe course of head lice, and a 34-year-old male patient with a severe form of post-steroid mycosis. In each of these cases, difficulties in making the correct diagnosis were highlighted, even though they represent some of the most common bacterial, viral, parasitic, and fungal dermatoses. The paper discusses the risk factors for these diseases, the pathophysiology of their atypical course, the effects and challenges in the therapeutic approach conducted. Infectious skin dermatoses require aggressive treatment and should never be underestimated.

Guilty or not guilty? - False positive results of common medicines in drug tests: review and practical guide.

Drug-abuse detection tests are becoming increasingly commonplace in patient care today and provide a rapid and effective method for identifying illicit substances. Occasionally, they may yield a positive result, indicating the presence of a substance, even though the individual has not consumed the suspected drug what sometimes can significantly impact both medical and legal decisions. The study outlines the substances that can lead to false-positive drug test results for amphetamines, cannabinoids, and benzodiazepines. The study's findings have revealed pivotal insights for patients receiving chronic treatment and their primary care physicians. Notably, amphetamine assays appear to be most prone to cross-reactivity with other substances. The beta-blocker group of medications, confirmed by various studies to interfere with amphetamine assays, could pose a substantial challenge in drug screening given its widespread use. Efavirenz also warrants mention, as it frequently triggers positive results for both benzodiazepine and cannabinoid assays among its users. This research helps highlight new areas for further investigation and aims to guide clinicians in their daily practice, especially when interpreting questionable positive drug-abuse test results. This comprehensive review serves as a valuable resource for clinicians to navigate false-positive scenarios effectively and maintain the highest standard of patient care.

Bridging the Gap in Cancer Research: Sulfur Metabolism of Leukemic Cells with a Focus on L-Cysteine Metabolism and Hydrogen Sulfide-Producing Enzymes.

Leukemias are cancers of the blood-forming system, representing a significant challenge in medical science. The development of leukemia cells involves substantial disturbances within the cellular machinery, offering hope in the search for effective selective treatments that could improve the 5-year survival rate. Consequently, the pathophysiological processes within leukemia cells are the focus of critical research. Enzymes such as cystathionine beta-synthase and sulfurtransferases like thiosulfate sulfurtransferase, 3-mercaptopyruvate sulfurtransferase, and cystathionine gamma-lyase play a vital role in cellular sulfur metabolism. These enzymes are essential to maintaining cellular homeostasis, providing robust antioxidant defenses, and supporting cell division. Numerous studies have demonstrated that cancerous processes can alter the expression and activity of these enzymes, uncovering potential vulnerabilities or molecular targets for cancer therapy. Recent laboratory research has indicated that certain leukemia cell lines may exhibit significant changes in the expression patterns of these enzymes. Analysis of the scientific literature and online datasets has confirmed variations in sulfur enzyme function in specific leukemic cell lines compared to normal leukocytes. This comprehensive review collects and analyzes available information on sulfur enzymes in normal and leukemic cell lines, providing valuable insights and identifying new research pathways in this field.

Ultrasound-Histopathological Presentation of Thyroid and Ovary Lesions in Adolescent Patients with DICER1 Syndrome: Case Reports and Literature Overview.

BACKGROUND: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic-solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli-Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. CONCLUSIONS: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening.

Hypotensive drugs mitigate the high-sodium diet-induced pro-inflammatory activation of mouse macrophages in vivo.

Nowadays, there is an increasing emphasis on the need to alleviate the chronic inflammatory response to effectively treat hypertension. However, there are still gaps in our understanding on how to achieve this. Therefore, research on interaction of antihypertensive drugs with the immune system is extremely interesting, since their therapeutic effect could partly result from amelioration of hypertension-related inflammation, in which macrophages seem to play a pivotal role. Thus, current comprehensive studies have investigated the impact of repeatedly administered hypotensive drugs (captopril, olmesartan, propranolol, carvedilol, amlodipine, verapamil) on macrophage functions in the innate and adaptive immunity, as well as if drug-induced effects are affected by a high-sodium diet (HSD), one of the key environmental risk factors of hypertension. Although the assayed medications increased the generation of reactive oxygen and nitrogen intermediates by macrophages from standard fed donors, they reversed HSD-induced enhancing effects on macrophage oxidative burst and secretion of pro-inflammatory cytokines. On the other hand, some drugs increased macrophage phagocytic activity and the expression of surface markers involved in antigen presentation, which translated into enhanced macrophage ability to activate B cells for antibody production. Moreover, the assayed medications augmented macrophage function and the effector phase of contact hypersensitivity reaction, but suppressed the sensitization phase of cell-mediated hypersensitivity under HSD conditions. Our current findings contribute to the recognition of mechanisms, by which excessive sodium intake affects macrophage immune activity in hypertensive individuals, and provide evidence that the assayed medications mitigate most of the HSD-induced adverse effects, suggesting their additional protective therapeutic activity.

Overreactive macrophages in SARS-CoV-2 infection: The effects of ACEI.

Among various factors influencing the course of SARS-CoV-2 infection in humans, macrophage overactivation is considered the main cause of the cytokine storm that leads to severe complications of COVID-19. Moreover, the increased expression of angiotensin converting enzyme 2 (ACE2), an obligatory entry receptor of the coronavirus, caused by treatment with ACE inhibitors (ACEI) lowered overall confidence in the safety of these drugs. However, analysis of the course of coronavirus infection in patients treated with ACEI does not support these concerns. Instead, the beneficial effect of ACEI on macrophages has increasingly been emphasized. This includes their anti-inflammatory activation and the consequent reduction in the risk of severe disease and life-threatening complications. Herein, we summarize the current knowledge and understanding of the dual role of macrophages in SARS-CoV-2 infection, with a special focus on the postulated mechanisms underlying the beneficial effects of macrophage targeting by ACEI. These seem to involve the stimulation of macrophage angiotensin II type 2 and Mas receptors by angiotensin 1-7, intensively produced due to the up-regulation of ACE2 expression on macrophages, as well as the direct inhibition of macrophage hyper-responsiveness by ACEI. The impact of ACEI on macrophages may also lead to the activation of an effective antiviral response due to the increased expression of ACE2.

The immunomodulatory effects of antihypertensive therapy: A review.

Hypertension remains the leading preventable risk factor for stroke and coronary artery disease, significantly contributing to all-cause global mortality and predisposing patients to renal and heart failure, as well as peripheral vascular disease. Due to the widespread usage of antihypertensive drugs, global mean blood pressure has remained unchanged or even slightly decreased over the past four decades. However, considering the broad spectrum of mechanisms involved in the action of antihypertensive drugs and the prevalence of their target receptors on immune cells, possible immunomodulatory effects which may exert beneficial effects of lowering blood pressure but also potentially alter immune function should be considered. In this review, we attempt to assess the consequences to immune system function of administering the five most commonly prescribed groups of antihypertensive drugs and to explain the mechanisms behind those interactions. Finally, we show potential gaps in our understanding of the effects of antihypertensive drugs on patient health. With regard to the widespread use of these drugs in the adult population worldwide, the discussed results may be of vital importance to evidence-based decision-making in daily clinical practice.