The Molecular Mechanisms Underlying the Systemic Effects Mediated by Parathormone in the Context of Chronic Kidney Disease.

Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone-Vitamin D-Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated "trade-off hypothesis" reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient's prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin-Angiotensin-Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.

Role of arterial hypertension and angiotensin II in chronic kidney disease (Review).

Chronic kidney disease (CKD) is a major public health issue, due to its effect on the quality of life of patients and by the huge costs incurred in treating this disease. It is an irreversible process, characterized by the progressive loss of functional nephrons. CKD ultimately requires the support of renal function by dialysis or even renal transplantation. It has a multiple etiology, but the most common causes remain arterial hypertension and diabetes. High arterial blood pressure affects the target organs (kidneys) and this leads to a vicious circle involved in maintaining high blood pressure. Arterial hypertension is closely related to the renal pathology of CKD. The result of excessive activation of the renin angiotensin system (RAS) is increased angiotensin II (Ang II), which acts upon the systemic circulation and especially upon the kidneys. The outcome is high blood pressure and also the stimulation of proinflammatory and profibrotic effects in the kidneys. Collectively these ultimately lead to CKD. The aim of this review was to provide a brief overview of the pathophysiological associations between CKD, arterial hypertension, and Ang II.

The RAAS Axis and SARS-CoV-2: From Oral to Systemic Manifestations.

One of the essential regulators of arterial blood pressure, the renin-angiotensin-aldosterone system (RAAS) seems to be one of the most complex mechanisms in the human body. Since the discovery of its key components and their actions, new substances and functions are still being unraveled. The main pathway begins with the secretion of renin in the kidney and culminates with the synthesis of angiotensin II (Ang II)-a strong vasoconstrictor-thanks to the angiotensin-converting enzyme (ACE). Research conducted in 2000 identified another enzyme, named ACE2, that converts Ang II into Ang-(1-7), a heptapeptide with opposing effects to those of Ang II: vasodilation and anti-inflammatory properties. This particular enzyme became of paramount importance during the last two decades, as a result of the confrontation of the human race with life-threatening epidemics. Multiple studies have been performed in order to uncover the link between ACE2 and human coronaviruses, the results of which we systemized in order to create an overview of the pathogenic mechanism. Human coronaviruses, such as SARS-CoV and SARS-CoV-2, attach to ACE2 via their spike proteins (S), causing the destruction of the enzyme. Because ACE2 limits the production of Ang II (by converting it into Ang-(1-7)), its destruction leads to a dysregulated inflammatory response. The purpose of this review is to decipher the complex pathophysiological mechanisms underlying the multiorgan complications (oral, cardiac, pulmonary, systemic) that appear as a result of the interaction of the SARS CoV-2 virus with the angiotensin-converting enzyme type 2.

The Impact of Angiotensin-Converting Enzyme-2/Angiotensin 1-7 Axis in Establishing Severe COVID-19 Consequences.

The COVID-19 pandemic has put a tremendous stress on the medical community over the last two years. Managing the infection proved a lot more difficult after several research communities started to recognize the long-term effects of this disease. The cellular receptor for the virus was identified as angiotensin-converting enzyme-2 (ACE2), a molecule responsible for a wide array of processes, broadly variable amongst different organs. Angiotensin (Ang) 1-7 is the product of Ang II, a decaying reaction catalysed by ACE2. The effects observed after altering the level of ACE2 are essentially related to the variation of Ang 1-7. The renin-angiotensin-aldosterone system (RAAS) is comprised of two main branches, with ACE2 representing a crucial component of the protective part of the complex. The ACE2/Ang (1-7) axis is well represented in the testis, heart, brain, kidney, and intestine. Infection with the novel SARS-CoV-2 virus determines downregulation of ACE2 and interrupts the equilibrium between ACE and ACE2 in these organs. In this review, we highlight the link between the local effects of RAAS and the consequences of COVID-19 infection as they arise from observational studies.

Connections between Orthopedic Conditions and Oxidative Stress: Current Perspective and the Possible Relevance of Other Factors, Such as Metabolic Implications, Antibiotic Resistance, and COVID-19.

The general opinion in the literature is that these topics remain clearly understudied and underrated, with many unknown aspects and with controversial results in the respective areas of research. Based on the previous experience of our groups regarding such matters investigated separately, here we attempt a short overview upon their links. Thus, we summarize here the current state of knowledge regarding the connections between oxidative stress and: (a) orthopedic conditions; (b) COVID-19. We also present the reciprocal interferences among them. Oxidative stress is, of course, an interesting and continuously growing area, but what exactly is the impact of COVID-19 in orthopedic patients? In the current paper we also approached some theories on how oxidative stress, metabolism involvement, and even antibiotic resistance might be influenced by either orthopedic conditions or COVID-19. These manifestations could be relevant and of great interest in the context of this current global health threat; therefore, we summarize the current knowledge and/or the lack of sufficient evidence to support the interactions between these conditions.

Vitamin D Deficiency in Both Oral and Systemic Manifestations in SARS-CoV-2 Infection: Updated Review.

The specialized literature emphasizes the fact that vitamin D has a potentially beneficial effect in the context of the current COVID-19 pandemic. The purpose of this article is to highlight the role of vitamin D, both prophylactic and curative, in the treatment of patients diagnosed with COVID-19. Even though its relevance is still unknown and causes various controversies, there is currently no specific treatment for patients diagnosed with COVID-19. There are various prevention strategies with new vaccination schedules, but additional randomized and clinical trials are still needed to combat this pandemic. In addition to the systemic manifestations of SARS-CoV-2 infection, oral manifestations of this disease have also been described in the literature. The etiology of oral manifestations associated with COVID-19 infection and vitamin D deficiency remains controversial. In the present studies, oral manifestations such as salivary gland infections, aphthae, erythema, gingivitis, ulcers, etc. have been reported. This is a new topic, and the prevalence of manifestations is described in only a few studies, which is inconsistent with the number of COVID-19 cases reported since the beginning of the pandemic. The clinical symptomatology in patients with current COVID-19 infection is polymorphic. Whether the oral manifestation is directly caused by SARS-CoV-2 or a secondary manifestation remains an important topic to analyze and discuss.

Involvement of proinflammatory cytokines in angiotensin II-induced hypertension in rat.

Rightfully considered as essential for hydro-electrolytic homeostasis, angiotensin II (Ang II) is the main product of the renin-angiotensin system (RAS). Ang II is one of the most important factors that contribute to the regulation of systemic arterial blood pressure (ABP). This major role is based on the effects exerted by RAS: Upon the kidney (RAS involvement in the control of salt and water excretion), upon the brain (RAS involvement in the control of water intake), and upon the sympathetic nervous system. It is currently known that there is a tight bidirectional link between high ABP and chronic kidney disease (CKD). Ang II causes vasoconstriction in the renal microvasculature, predominantly in the preglomerular arterioles. High ABP affects the target organs (eyes, brain, heart, kidneys) and it is known both as a cause and as an effect of CKD. Thus, there is a positive feedback mechanism that contributes even more to the increase in ABP and the progression of CKD. Along with its main hemodynamic effects, Ang II has direct proinflammatory actions, that also affect the structure and function of the kidney and heart. This study investigated the role of RAS and Ang II in the inflammation that accompanies the hypertension experimentally induced by Ang II in rats. Our data support the hypothesis that anti-inflammatory medication might alleviate the morphological and/or functional changes of the kidneys and heart that are related to Ang II-induced hypertension.

Acute coronary syndrome with ST segment elevation in a patient with Addison disease: Case report and brief review of physiopathological mechanisms: A case study.

The adrenal gland serve important roles in the modulation of the immune response, the adjustment of blood pressure, the stress reaction via glucocorticoids and the hydroelectrolytic balance via mineralocorticoids. Primary adrenal insufficiency, known as Addison disease, is characterized by a decrease in glucocorticoid secretion (cortisol) and, more rarely, by a hyposecretion of mineralocorticoids (aldosterone). The production of cortisol, which is a hormone that helps the body respond to stress, is regulated in the brain, the hypothalamus and the pituitary gland. The hypothalamus stimulates the pituitary gland to produce adrenocorticotropic hormone, which stimulates cortisol production from the adrenal gland. If left untreated, Addison disease has a high mortality rate. Corticotherapy used in the treatment of Addison disease is associated with a certain cardiovascular risk. The proatherogenic effect of corticoids is based on the chronic inflammatory response of the vascular wall to a series of events. The aim of the current case report was to review the pathophysiological mechanisms and interactions that may lead to the onset of acute coronary syndrome with ST elevation in a patient with Addison disease.

Synthesis and physiological implications of melanic pigments.

The process of melanin synthesis and distribution is called melanogenesis, a process that is based on melanocytes present among the basal cells of the epidermis. Pigments formed in melanocyte melanosomes are then stored in the basal layer of epidermal cells, as well as in dermal macrophages, which become melanophores. From the embryological point of view, melanocytes derive from the melanoblasts of the neural crest, from where they migrate during the first months of life into the skin, eye, cochlea, bone, peripheral nervous system, heart and adipose tissue. The melanic pigments, eumelanin and pheomelanin, are the final product of complex biochemical reactions starting from the amino acid L-tyrosine. Melanin has a major role in skin homeostasis through the photoprotection it offers from the harmful effect of ultraviolet radiation. Melanin absorbs and/or reflects ultraviolet radiation but is also involved in the neutralizing process of free radicals and reactive oxygen species. Pigmentogenesis is a dependent oxygen process and is controlled by intrinsic factors (genetic and hormonal) as well as extrinsic factors (ultraviolet radiation). Melanogenesis is stimulated by stimulant melanocytic hormone, adrenocorticotropin hormone, estrogens and progesterone. The present review aimed to provide a summary of recent data about melanogenesis physiology.

Changes in arterial stiffness following dialysis in relation to overhydration and to endothelial function.

INTRODUCTION: Cardiovascular (CV) morbidity and mortality are greatly enhanced in patients with chronic kidney disease, partly due to increased arterial stiffness. MATERIAL AND METHOD: The study included 63 stable HD patients. Stiffness parameters were evaluated by applanation tonometry before the mid-week HD sessions. Pre-HD bioimpedance parameters were measured. A phase angle 6°. Overhydration increases arterial stiffness, but has no influence on either EID or ED vascular reactivity. CONCLUSION: In hemodialysis, volume overload is an important contributor to increased arterial stiffness and modifies cardiovascular status especially by LV hypertrophy. Achieving normohydration may significantly ameliorate cardiac abnormalities and arterial stiffness and may impact major clinical events and CV mortality.

Idazoxan effects upon contractile activity in the rat aorta are related to alpha adrenoceptors and L-type channels.

Idazoxan is an alpha(2) adrenoceptor antagonist and alpha(1)/alpha(2) partial agonist which also blocks imidazoline receptors. Although idazoxan is widely used in pharmacological studies, its intrinsic vasoactive properties could bring about some limitations. Others have shown that in rat aorta contracted by phenylephrine idazoxan induces relaxation and that in rat small arteries it preferentially antagonizes the alpha(1)-mediated response. We further investigated this matter, using the rat aorta and focusing on the endothelium-independent effects and on L-type channels. In our study, idazoxan inhibited the contraction induced by phenylephrine, an effect which was stronger in the presence of endothelium, but did not affect the contractions induced by various other agents (high potassium, angiotensin II, prostaglandin F(2alpha)). This preferential inhibition was attenuated by 10(-4) m, but not by 10(-5) m yohimbine, and also reduced by 10(-2) m tetraethylammonium and blunted by 10(-4) m methoxyverapamil. In concentrations above 10(-5) m idazoxan induced weak contractions of the de-endothelized rings, which were prazosin- and methoxyverapamil-sensitive. Others have suggested that cyclic guanosine monophospate mediates the idazoxan-induced endothelium-dependent relaxation, but this is difficult to reconcile with our findings. Potassium efflux could play some role in the direct relaxing effect of idazoxan. The observed idazoxan effects appear as based on action upon alpha(1) receptors, but a direct interaction with L-type calcium channels could also be taken into consideration.