cardiovascular-agents and Immune-System-Diseases

Male and female sexual dysfunction (SD) is considered a multifactorial condition. Numerous studies have shown the involvement of inflammatory processes in this pathological condition. Sexual intercourse requires healthy and functioning vessels to supply the pelvic region in both males and females, generating penile erection and clitoral and vaginal lubrication, respectively. Cardiovascular diseases and associated risk factors may contribute negatively to pelvic blood flow, possibly through immune system activation.. The study aimed to address the correlation between vascular inflammation driven by immune system activation and SD in males and females.. A literature review was performed to identify articles addressing male and female SD and vascular inflammation. Key words included "male and female sexual dysfunction," "vascular inflammation," "iliac and pudendal arteries dysfunction," "genitourinary tract," and "blood flow.". Management of systemic and local inflammation may be a useful alternative to improve SD and reduce the risk of cardiovascular diseases in the future.. Increased levels of cytokines and chemokines have been detected in humans and animals with hypertension, obesity, and diabetic conditions. Chronic activation of the innate immune system, especially by pathogen- or damage-associated molecular patterns, and metabolic-related disorders may act as triggers further contributing to an increased inflammatory condition. Due to the reduced size of vessels, SD and retinal vascular impairments have been shown to be predictive factors for cardiovascular diseases. Therefore, considering that blood flow to the genitalia is essential for sexual function, endothelial dysfunction and vascular remodeling, secondary to chronic immune system activation, may be implicated in male and female vasculogenic SD.. Several conditions appear to play a role in SD. In the present review, we have identified a role for the immune system in generating vascular and tissue impairments contributing to erectile dysfunction and female SD. Calmasini FB, Klee N, Webb RC, et al. Impact of Immune System Activation and Vascular Impairment on Male and Female Sexual Dysfunction. Sex Med Rev 2019;7:604-613.

Topics: Cardiovascular Agents; Cytokines; Diabetes Complications; Dyslipidemias; Female; Genitalia, Female; Genitalia, Male; Gonadal Steroid Hormones; Humans; Hypertension; Immune System Diseases; Immunity, Innate; Male; Obesity; Sexual Dysfunction, Physiological; Vascular Diseases; Vasculitis

Phospholipase D2 (PLD2) is a lipid-signaling enzyme that produces the signaling molecule phosphatidic acid (PA) by catalyzing the hydrolysis of phosphatidylcholine (PC). The molecular characteristics of PLD2, the mechanisms of regulation of its activity, its functions in the signaling pathway involving PA and binding partners, and its role in cellular physiology have been extensively studied over the past decades. Although several potential roles of PLD2 have been proposed based on the results of molecular and cell-based studies, the pathophysiological functions of PLD2 in vivo have not yet been fully investigated at the organismal level. Here, we address accumulated evidences that provide insight into the role of PLD2 in human disease. We summarize recent studies using animal models that provide direct evidence of the function of PLD2 in several pathological conditions such as vascular disease, immunological disease, and neurological disease. In light of the use of recently developed PLD2-specific inhibitors showing potential in alleviating pathological conditions, improving our understanding of the role of PLD2 in human disease would be necessary to target the regulation of PLD2 activity as a therapeutic strategy.

Topics: Animals; Antineoplastic Agents; Cardiovascular Agents; Gene Expression Regulation; Humans; Immune System Diseases; Immunologic Factors; Mice; Neoplasms; Nervous System Diseases; Neuroprotective Agents; Phosphatidic Acids; Phosphatidylcholines; Phospholipase A2 Inhibitors; Phospholipase D; Signal Transduction; Vascular Diseases

The macrocycles representing a unique chemical structure bridging conventional small molecules and large biomolecules, have attracted more and more attention in drug discovery over the past decade, and tremendous progress has been made toward the macrocyclization synthesis and structure diversification recently. Because of their favored size, flexibility and complexity, macrocycles can engage previously undruggable targets through numerous and spatially distributed binding interactions, and offer many privileged features including high potency, prominent selectivity, as well as favorable pharmacokinetics properties, and unique intellectual property(IP) space, and even safety profiles, etc. Currently around 70 macrocyclic molecules have been approved for clinical therapy, over 76 macrocycles are being evaluated in clinical trials from phase I to phase III. It is believed that the macrocycles will play more and more important role in the future, and provide very distinctive and promising opportunities for drug discovery along with the development of synthetic methodology, phenotypical screening, and computational studies.

Topics: Anti-Infective Agents; Antineoplastic Agents, Phytogenic; Cardiovascular Agents; Cardiovascular Diseases; Drug Discovery; Humans; Immune System Diseases; Macrocyclic Compounds; Neoplasms

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Antirheumatic Agents; Bacterial Vaccines; Cardiovascular Agents; Central Nervous System Agents; Drug Therapy; Endocrine System Diseases; Female Urogenital Diseases; Gastrointestinal Agents; Humans; Immune System Diseases; Male Urogenital Diseases; Pneumococcal Vaccines; Streptococcus pneumoniae

Topics: Anaphylaxis; Animals; Cardiovascular Agents; Ergot Alkaloids; Hypersensitivity; Immune System Diseases; Rabbits