- Hyponatremia in kidney transplant patients: its pathophysiologic mechanisms. [Journal Article]
- CKClin Kidney J 2018; 11(4):581-585
- Kidney transplant patients (KTPs), and particularly those with advanced chronic kidney rejection, may be affected by opportunistic infections, metabolic alterations and vascular and oncologic disease...
Kidney transplant patients (KTPs), and particularly those with advanced chronic kidney rejection, may be affected by opportunistic infections, metabolic alterations and vascular and oncologic diseases that promote clinical conditions that require a variety of treatments, the combinations of which may predispose them to hyponatremia. Salt and water imbalance can induce abnormalities in volemia and/or serum sodium depending on the nature of this alteration (increase or decrease), its absolute magnitude (mild or severe) and its relative magnitude (body sodium:water ratio). Hyponatremia appears when the body sodium:water ratio is reduced due to an increase in body water or a reduction in body sodium. Additionally, hyponatremia is classified as normotonic, hypertonic and hypotonic and while hypotonic hyponatremia is classified in hyponatremia with normal, high or low extracellular fluid. The main causes of hyponatremia in KTPs are hypotonic hyponatremia secondary to water and salt contraction with oral hydration (gastroenteritis, sepsis), free water retention (severe renal failure, syndrome of inappropriate antidiuretic hormone release, hypothyroidism), chronic hypokalemia (rapamycin, malnutrition), sodium loss (tubular dysfunction secondary to nephrocalcinosis, acute tubular necrosis, tubulitis/rejection, interstitial nephritis, adrenal insufficiency, aldosterone resistance, pancreatic drainage, kidney-pancreas transplant) and hyponatremia induced by medication (opioids, cyclophosphamide, psychoactive, potent diuretics and calcineurinic inhibitors). In conclusion, KTPs are predisposed to develop hyponatremia since they are exposed to immunologic, infectious, pharmacologic and oncologic disorders, the combinations of which alter their salt and water homeostatic capacity.
- The prognostic factors of HIV-negative adult cryptococcal meningitis with a focus on cranial MRI-based neuroimaging findings. [Journal Article]
- JCJ Clin Neurosci 2018 Jul 02
- The prognostic significance of clinical characteristics and neuroimaging features, especially cranial magnetic resonance imaging (MRI)-based neuroimaging features, in patients with human immunodefici...
The prognostic significance of clinical characteristics and neuroimaging features, especially cranial magnetic resonance imaging (MRI)-based neuroimaging features, in patients with human immunodeficiency virus (HIV)-negative cryptococcal meningitis (CM) has rarely been examined in the literature. We analyzed the clinical characteristics and MRI findings of 65 HIV-negative patients (43 men, 22 women, age 19-86 years) collected during a study period of 15 years (January 2001-December 2015). Their underlying conditions included diabetes mellitus, liver cirrhosis, hematologic disorders, autoimmune disorders, malignancy, chronic obstructive pulmonary disease, adrenal insufficiency and organ transplantation, and their clinical presentations included headache, altered consciousness, fever, seizure, visual disturbance and hearing impairment. The main cranial MRI findings were basal meningeal enhancement (44.6%, 29/65), dilated Virchow-Robin space/pseudocyst (43.1%, 28/65), "dirty" cerebrospinal fluid sign (38.5%, 25/65), hydrocephalus (36.9%, 21/65), acute/subacute cerebral infarct (ASCI, 21.5%, 14/65), cryptococcoma (9.2%, 6/65), and hazy brain base (1.5%, 1/65). The therapeutic results of the 65 patients were evaluated using the Glasgow Outcome Scale (GOS). A comparison of the good outcome group (GOS score = 4-5, n = 37) and poor outcome group (GOS score = 1-3, n = 28) revealed that both the presence of seizures and ASCI were significantly associated with the prognosis. A comparison of the groups with ASCI (n = 14) and without ASCI (n = 51) revealed that the presence of basal meningeal enhancement was a significant factor for the development of ASCI, and that this correlation may be associated with intense basal meningeal inflammation in adjacent small vessels.
- Dehydroepiandrosterone Research: Past, Current, and Future. [Journal Article]
- VHVitam Horm 2018; 108:1-28
- The discovery of "oestrus-producing" hormones was a major research breakthrough in biochemistry and pharmacology during the early part of the 20th century. The elucidation of the molecular weight and...
The discovery of "oestrus-producing" hormones was a major research breakthrough in biochemistry and pharmacology during the early part of the 20th century. The elucidation of the molecular weight and chemical structure of major oxidative metabolites of dehydroepiandrosterone (DHEA) led to the award of the Nobel Prize in 1939 to Adolf Frederick Johann Butenandt and Leopold Ruzicka. Considered a bulk androgen in the circulation, DHEA and its sulfated metabolite DHEA-S can be taken up by most tissues where the sterols are metabolized to active androgenic and estrogenic compounds needed for growth and development. Butenandt's interactions with the German pharmaceutical company Schering led to production of gram quantities of these steroids and other chemically modified compounds of this class. Sharing chemical expertise allowed Butenandt's laboratory at the Kaiser Wilhelm Institute to isolate and synthesize many steroid compounds in the elucidation of the pathway leading from cholesterol to testosterone and estrogen derivatives. As a major pharmaceutical company worldwide, Schering AG sought these new biological sterols as pharmacological agents for endocrine-related diseases, and the European medical community tested these compounds in women for conditions such as postmenopausal depression, and in men for increasing muscle mass. Since it was noted that circulating DHEA-S levels decline as a function of age, experimental pathology experiments in animals were performed to determine how DHEA may protect against cancer, diabetes, aging, obesity, immune function, bone density, depression, adrenal insufficiency, inflammatory bowel disease, diminished sexual function/libido, AIDS/HIV, chronic obstructive pulmonary disease, coronary artery disease, chronic fatigue syndrome, and metabolic syndrome. While the mechanisms by which DHEA ameliorates these conditions in animal models have been elusive to define, even less is known about its role in human disease, other than as a precursor to other sterols, e.g., testosterone and estradiol. Our groups have shown that DHEA and many of its oxidative metabolites serve as a low-affinity ligands for hepatic nuclear receptors, such as the pregnane X receptor, the constitutive androstane receptor, and estrogen receptors α/β (ERα/ERβ) as well as G protein-coupled ER (GPER1). This chapter highlights the founding research on DHEA from a historical perspective, provides an overview of DHEA biosynthesis and metabolism, briefly summarizes the early work on the beneficial effects attributed to DHEA in animals, and summarizes the human trials addressing the action of DHEA as a therapeutic agent. In general, most human studies involve weak correlations of circulating levels of DHEA and disease outcomes. Some support for DHEA as a therapeutic compound has been demonstrated for postmenopausal women, in vitro fertilization, and several autoimmune disorders, and adverse health effects, such as, acne, embryo virilization during pregnancy, and possible endocrine-dependent cancers.
- Opioid-Induced Adrenal Insufficiency. [Review]
- MCMayo Clin Proc 2018; 93(7):937-944
- One in 10 Americans experience chronic pain. Although opioids do play a role in the management of pain, long-term opioid use may lead to adverse effects. Endocrine-related adverse effects have been d...
One in 10 Americans experience chronic pain. Although opioids do play a role in the management of pain, long-term opioid use may lead to adverse effects. Endocrine-related adverse effects have been described but remain poorly recognized. Opioid-induced adrenal insufficiency occurs because of suppression of hypothalamic-pituitary-adrenal communication and may be challenging to diagnose but has been reported in 9% to 29% of patients receiving long-term opiate therapy. Little data exist to guide case detection and patient management. Treatment includes cessation of opiates (the inciting factor) if possible and glucocorticoid replacement.
- [Paracoccidioidomycosis: chronicle of a neglected disease]. [Journal Article]
- MMedicina (B Aires) 2018; 78(3):180-184
- Paracoccidioidomycosis (PCM) is among the systemic mycoses which are endemic only in Latin America. In Argentina, the vast majority of the cases are reported at north of latitude 34.5° S. The disease...
Paracoccidioidomycosis (PCM) is among the systemic mycoses which are endemic only in Latin America. In Argentina, the vast majority of the cases are reported at north of latitude 34.5° S. The disease is produced by thermodimorphic fungi of the genus Paracoccidoides: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), P. venezuelensis (PS4) y P. lutzii. The natural habitat of members of this genus is the soil, where they produce infectious conidia. Little is known, however, about their specific ecologic niche(s), and this knowledge gap hampers the design of measures to control the infection. Rural male workers are the group most at risk of developing PCM. Infection occurs by inhalation of aerosolized conidia and may either be asymptomatic or cause mild respiratory symptoms. In turn, this primary infection may be self-limited or progress to severe pulmonary or disseminated disease. The disease has two clinical presentations: (i) acute or subacute (juvenile), frequent in children, adolescents and people with immunodeficiencies; and (ii) chronic progressive, in adults. Active lesions often resolve into fibrotic scars which can cause dysphagia, dysphonia, adrenal insufficiency, and intestinal obstruction. Although efficient tools are available for diagnosis and treatment, the nonspecific nature of PCM clinical manifestations frequently delay the diagnosis. In addition, the poor adherence to long antifungal treatments allows the advance of the disease and the development of extensive fibrosis compromising severely and permanently respiratory and adrenal functions, thus altering the patient"s quality of life and even causing his/her death.
- [CME: Adrenal Insufficiency]. [Journal Article]
- PPraxis (Bern 1994) 2018; 107(13):717-725
- CME: Adrenal Insufficiency Abstract. Patients suffering from adrenal insufficiency (AI) often present with unspecific symptoms. Therefore, the diagnosis of AI, a potential life-threatening condition,...
CME: Adrenal Insufficiency Abstract. Patients suffering from adrenal insufficiency (AI) often present with unspecific symptoms. Therefore, the diagnosis of AI, a potential life-threatening condition, can be missed. Lab tests, especially the ACTH-stimulation test, play a crucial role in the diagnosis of AI. According to the different etiologies, AI can be grouped into a primary (adrenal) or central (hypothalamic or pituitary, respectively) form. However, the most common cause is the treatment with glucocorticoids, which can lead to central AI. Patients suffering from AI are given hydrocortisone. The chronic replacement dose should be as low as possible, in acute situations, a rapid and sufficient increase of the hydrocortisone dose is necessary to prevent adrenal crisis. Replacement therapy with fludrocortisone is only necessary in patients with primary AI.
- Relative adrenal insufficiency in cirrhotic patients with ascites (hepatoadrenal syndrome). [Journal Article]
- DLDig Liver Dis 2018 May 23
- CONCLUSIONS: RAI is common in non-septic cirrhotic patients with ascites and its prevalence increases with severity of liver disease. However, it does not affect the short-term outcome in these patients.
- [Chronic adrenal insufficiency: an underestimated cause of chronic fatigue]. [Case Reports]
- PAPan Afr Med J 2018; 29:93
- Chronic adrenal insufficiency is regarded as a rare disease in its primary stage. However, secondary adrenal insufficiency, which essentially occurs after stopping corticosteroids, is more frequent, ...
Chronic adrenal insufficiency is regarded as a rare disease in its primary stage. However, secondary adrenal insufficiency, which essentially occurs after stopping corticosteroids, is more frequent, ranging from 4.2% to 60%, depending on the pathology treated, but it is often unrecognized. We report the case of a 66 year old female patient with a history of chronic fatigue for more than 2 years. The patient consulted several clinicians but symptoms were wrongly attributed to a depressive disorder rather than to adrenal corticotropic adrenal insufficiency.
- Nicotinamide Nucleotide Transhydrogenase as a novel treatment target in adrenocortical carcinoma. [Journal Article]
- EEndocrinology 2018 Apr 20
- Adrenocortical Carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. Here we evaluated a potential new treatment target for ACC, focusing on the mitochondrial NADPH generato...
Adrenocortical Carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. Here we evaluated a potential new treatment target for ACC, focusing on the mitochondrial NADPH generator Nicotinamide Nucleotide Transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized NNT silencing in ACC cells will induce toxic levels of oxidative stress. To explore this, we transiently knocked down NNT in NCI-H295R ACC cells. As predicted, this manipulation increased intracellular levels of oxidative stress; this resulted in a pronounced suppression of cell proliferation and higher apoptotic rates, as well as sensitization of cells to chemically-induced oxidative stress. Steroidogenesis was paradoxically stimulated by NNT loss, as demonstrated by mass spectrometry-based steroid profiling. Next, we generated a stable NNT knockdown model in the same cell line to investigate the longer-lasting effects of NNT silencing. After long-term culture, cells adapted metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remained suppressed. This was associated with higher rates of oxygen consumption. The molecular pathways underpinning these responses were explored in detail by RNA sequencing and non-targeted metabolome analysis, revealing major alterations in nucleotide synthesis, protein folding and polyamine metabolism. Our study provides the first pre-clinical evidence of the therapeutic merit of antioxidant targeting in ACC as well as illuminating the long-term adaptive response of cells to oxidative stress.
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- Postnatal relative adrenal insufficiency results in methylation of the glucocorticoid receptor gene in preterm infants: a retrospective cohort study. [Journal Article]
- CEClin Epigenetics 2018; 10:66
- CONCLUSIONS: The results of this study indicate that a prenatal environment that results in intrauterine growth restriction and postnatal relative adrenal insufficiency requiring glucocorticoid administration leads to GR gene methylation. That, in turn, may result in neurodevelopmental disabilities.