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Journal of the American College of... Jan 2020Peripartum cardiomyopathy is a form of systolic heart failure affecting young women toward the end of pregnancy or in the months following delivery. Incidence is higher... (Review)
Review
Peripartum cardiomyopathy is a form of systolic heart failure affecting young women toward the end of pregnancy or in the months following delivery. Incidence is higher in African-American women and in women with older maternal age, hypertensive disorders of pregnancy, and multiple gestation pregnancies. Symptoms of heart failure mimic those of normal pregnancy, often resulting in a delay in diagnosis and preventable complications. Echocardiography showing decreased myocardial function is essential for the diagnosis. Medical management is similar to heart failure with reduced ejection fraction of other etiologies, but adjustments during pregnancy are necessary to ensure fetal safety. Variable outcomes include complete recovery, persistent heart failure, arrhythmias, thromboembolic events, and death. Subsequent pregnancy confers substantial risk of relapse and even death if there is incomplete myocardial recovery. Additional research about the etiology, optimal therapy including the use of bromocriptine, long-term outcomes, and duration of treatment after recovery are needed.
Topics: Cardiomyopathies; Cardiovascular Agents; Female; Humans; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Review Literature as Topic
PubMed: 31948651
DOI: 10.1016/j.jacc.2019.11.014 -
The Veterinary Clinics of North... May 2022Pyometra is a common disease in intact bitches and queens and occurs, although less frequently,in most other female pets. The illness is generally diagnosed within 4... (Review)
Review
Pyometra is a common disease in intact bitches and queens and occurs, although less frequently,in most other female pets. The illness is generally diagnosed within 4 months after estrus, in middle-aged to older bitches and queens. Hormonal and bacterial factors are important for the disease development, and progesterone plays a key role. The diagnosis is based on case history, clinical signs, and findings on physical examination, laboratory analyses and diagnostic imaging. Pyometra is potentially life-threatening and considered a medical emergency. Surgical ovariohysterectomy is the safest and most efficient treatment, but purely pharmacologic options are possible in less severe cases.
Topics: Animals; Dog Diseases; Dogs; Endometrial Hyperplasia; Female; Hysterectomy; Progesterone; Pyometra
PubMed: 35465903
DOI: 10.1016/j.cvsm.2022.01.004 -
The Veterinary Clinics of North... Jul 2018Pyometra is a common disease in dogs and cats. Hormones and opportunistic bacteria are fundamental in the development, with progesterone playing a key role. The disease... (Review)
Review
Pyometra is a common disease in dogs and cats. Hormones and opportunistic bacteria are fundamental in the development, with progesterone playing a key role. The disease should be suspected in intact bitches and queens presenting with illness, and particularly if within 4 months after estrus. Early diagnosis and treatment are vital to increase chances of survival as endotoxemia and sepsis often are induced. Typical clinical signs include vaginal discharge, depression, anorexia, polyuria and polydipsia, fever and gastrointestinal disturbances. Surgical ovariohysterectomy is the safest and most effective treatment. For breeding animals with less severe illness, purely medical treatments alternatives are possible.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Hysterectomy; Ovariectomy; Pyometra
PubMed: 29933767
DOI: 10.1016/j.cvsm.2018.03.001 -
Medicina (Kaunas, Lithuania) Aug 2022Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have... (Review)
Review
Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have traditionally been the primary treatment for the majority of prolactinomas, with surgery considered the second line. The aim of this review is to examine the historical and modern management of prolactinomas, including medical therapy with DAs, transsphenoidal surgery, and multimodality therapy for the treatment of aggressive prolactinomas and metastatic PitNETs, with an emphasis on the efficacy, safety, and future directions of current therapeutic modalities. DAs have been the mainstay of prolactinoma management since the 1970s, initially with bromocriptine and more recently with cabergoline. Cabergoline normalizes prolactin in up to 85% of patients and causes tumor shrinkage in up to 80%. Primary surgical resection of microprolactinomas and enclosed macroprolactinomas performed by experienced pituitary neurosurgeons have similar remission rates to cabergoline. Aggressive prolactinomas and metastatic PitNETS should receive multimodality therapy including high dose cabergoline, surgery, radiation therapy (preferably using stereotactic radiosurgery where suitable), and temozolomide. DAs remain a reliable mode of therapy for most prolactinomas but results from transsphenoidal surgery in expert hands have improved considerably over the last one to two decades. Surgery should be strongly considered as primary therapy, particularly in the setting of microprolactinomas, non-invasive macroprolactinomas, or prior to attempting pregnancy, and has an important role in the management of DA resistant and aggressive prolactinomas.
Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Female; Humans; Pituitary Neoplasms; Pregnancy; Prolactinoma; Treatment Outcome
PubMed: 36013562
DOI: 10.3390/medicina58081095 -
Frontiers in Endocrinology 2022Over the last years, the metabolic role of PRL has emerged. PRL excess is known to promote weight gain, obesity, metabolic syndrome, and impairment in gluco-insulinemic... (Review)
Review
Over the last years, the metabolic role of PRL has emerged. PRL excess is known to promote weight gain, obesity, metabolic syndrome, and impairment in gluco-insulinemic and lipid profiles, likely due to the suppression of physiologic dopaminergic tone. Prolactin receptors and dopamine receptors type 2 have been demonstrated to be expressed on both human pancreatic β- cell and adipocytes, supporting a key role of prolactin and dopamine in peripheral metabolic regulation. Medical treatment with the dopamine agonists bromocriptine and cabergoline has been demonstrated to decrease the prevalence of metabolic syndrome and obesity, and significantly improve gluco-insulinemic and lipid profiles. In hyperprolactinemic men with concomitant hypogonadism, correction of hyperprolactinaemia and testosterone replacement has been proven to restore metabolic impairment. In turn, low prolactin levels have also been demonstrated to exert a detrimental effect on weight gain, glucose and lipid metabolism, thus leading to an increased prevalence of metabolic syndrome. Therefore, PRL values ranging from 25 to 100 mg/L, in absence of other recognizable pathological causes, have been proposed to represent a physiological response to the request for an increase in metabolic activity, and nowadays classify the so-called HomeoFIT- PRL as a promoter of metabolic homeostasis. The current review focuses mainly on the effects of hyperprolactinemia and its control by medical treatment with DAs on the modulation of food intake, body weight, gluco-insulinemic and lipid profile. Furthermore, it provides the latest knowledge about the metabolic impact of hypoprolactinemia.
Topics: Bromocriptine; Cabergoline; Dopamine; Dopamine Agonists; Glucose; Humans; Hyperprolactinemia; Lipids; Male; Metabolic Syndrome; Obesity; Prolactin; Receptors, Dopamine; Receptors, Prolactin; Testosterone; Weight Gain
PubMed: 36237192
DOI: 10.3389/fendo.2022.1015520 -
International Journal of Molecular... Mar 2017Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging... (Review)
Review
Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson's disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson's disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS) structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin-proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina), and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine), monoamine oxidase (MAO) inhibitors (selegiline, rasagiline), and catechol--methyltransferase (COMT) inhibitors (entacapone, tolcapone). The chronic administration of antiparkinsonian drugs currently induces the "wearing-off phenomenon", with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in addition to enhancing dopaminergic neurotransmission. Since biochemical changes and therapeutic outcomes are highly dependent upon the genomic profiles of PD patients, personalized treatments should rely on pharmacogenetic procedures to optimize therapeutics.
Topics: Adult; Aged; Aged, 80 and over; Animals; Antiparkinson Agents; Disease Susceptibility; Dopaminergic Neurons; Humans; Middle Aged; Oxidative Stress; Parkinson Disease; Pharmacogenetics; Pharmacogenomic Variants; Risk Factors
PubMed: 28273839
DOI: 10.3390/ijms18030551 -
Cell Feb 2021The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the...
The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-G and D2R-G signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system.
Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amino Acid Sequence; Conserved Sequence; Cryoelectron Microscopy; Cyclic AMP; GTP-Binding Proteins; HEK293 Cells; Humans; Ligands; Models, Molecular; Mutant Proteins; Receptors, Adrenergic, beta-2; Receptors, Dopamine D1; Receptors, Dopamine D2; Signal Transduction; Structural Homology, Protein
PubMed: 33571431
DOI: 10.1016/j.cell.2021.01.027 -
European Journal of Heart Failure Jul 2019Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition typically presenting as heart failure with reduced ejection fraction (HFrEF) in the last...
Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy.
Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition typically presenting as heart failure with reduced ejection fraction (HFrEF) in the last month of pregnancy or in the months following delivery in women without another known cause of heart failure. This updated position statement summarizes the knowledge about pathophysiological mechanisms, risk factors, clinical presentation, diagnosis and management of PPCM. As shortness of breath, fatigue and leg oedema are common in the peripartum period, a high index of suspicion is required to not miss the diagnosis. Measurement of natriuretic peptides, electrocardiography and echocardiography are recommended to promptly diagnose or exclude heart failure/PPCM. Important differential diagnoses include pulmonary embolism, myocardial infarction, hypertensive heart disease during pregnancy, and pre-existing heart disease. A genetic contribution is present in up to 20% of PPCM, in particular titin truncating variant. PPCM is associated with high morbidity and mortality, but also with a high probability of partial and often full recovery. Use of guideline-directed pharmacological therapy for HFrEF is recommended in all patients respecting contraindications during pregnancy/lactation. The oxidative stress-mediated cleavage of the hormone prolactin into a cardiotoxic fragment has been identified as a driver of PPCM pathophysiology. Pharmacological blockade of prolactin release using bromocriptine as a disease-specific therapy in addition to standard therapy for heart failure treatment has shown promising results in two clinical trials. Thresholds for devices (implantable cardioverter-defibrillators, cardiac resynchronization therapy and implanted long-term ventricular assist devices) are higher in PPCM than in other conditions because of the high rate of recovery. The important role of education and counselling around contraception and future pregnancies is emphasised.
Topics: Cardiomyopathies; Diagnosis, Differential; Echocardiography; Electrocardiography; Europe; Female; Heart Failure; Humans; Patient Care Management; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Puerperal Disorders; Societies, Medical; Stroke Volume
PubMed: 31243866
DOI: 10.1002/ejhf.1493