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1.
Pediatr Dermatol ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627999

ABSTRACT

While ulceration is one of the most common infantile hemangioma (IH) complications, severe bleeding is a rare consequence, with a paucity of patients reported. We report a 5-month-old girl with a very large, mixed, partial segmental IH of the upper chest wall who, despite medical intervention, developed severe ulceration and multiple episodes of life-threatening bleeding that ultimately led to hemorrhagic shock. Experience in our patient and a review of six previous reports shows that severe bleeding is a risk when ulceration extends directly into an arterial feeding vessel that is often visible clinically. Other potential predictors for severe bleeding include large to very large IH size with extension of the tumor into underlying structures, segmental or partial segmental patterning, mixed and bulky morphology, and white discoloration as a sign of impending or worsening ulceration.

3.
Am J Respir Crit Care Med ; 209(2): 137-152, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37772985

ABSTRACT

Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1) recommends the use of mycophenolate; 2) recommends further research into the safety and efficacy of (a) pirfenidone and (b) the combination of pirfenidone plus mycophenolate; and 3) suggests the use of (a) cyclophosphamide, (b) rituximab, (c) tocilizumab, (d) nintedanib, and (e) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.


Subject(s)
Lung Diseases, Interstitial , Scleroderma, Systemic , Humans , United States , Immunosuppressive Agents/therapeutic use , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Cyclophosphamide/therapeutic use , Rituximab/therapeutic use , Scleroderma, Systemic/complications , Lung
4.
Eur Radiol ; 33(7): 4746-4757, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36786906

ABSTRACT

OBJECTIVES: Interstitial lung disease (ILD) impacts mortality in antisynthetase syndrome (ASyS). Computed tomographic (CT) patterns and evolution in ASyS ILD are not well described. We report longitudinal CT patterns in ASyS-ILD and their impact on survival. METHODS: This is a monocentric retrospective study of 47 patients with ASyS-ILD. Longitudinal CT patterns and fibrosis severity (severity of radiographic features indicating fibrosis) were analyzed by two radiologists in consensus. The association between imaging features and survival was examined using univariate Cox regression analysis. RESULTS: In total, 211 CT scans were analyzed with an average of 4 ± 2 CT scans/patient with a median follow-up of 79 months in 47 patients. Non-fibrotic patterns were present initially in 63.8% (n = 30) of patients, while fibrotic patterns occurred in 36.2% (n = 17). The initial non-fibrotic patterns/abnormalities resolved in 23.3% (n = 7), evolved in 6.7% (n = 2), persisted in 13.3% (n = 4), and progressed in 56.7% (n = 17), while initial fibrotic patterns persisted in 82.4% (n = 14) and progressed in 17.6% (n = 3). Radiographic progression of ILD (progression in CT pattern or increased fibrosis severity) occurred in 53.2% (n = 25) of patients. Advanced age and radiographic progression were associated with decreased survival (all p < 0.05). The presence of ground-glass opacities (GGO) and predominant lower lung distribution of abnormalities on initial CTs were associated with increased survival (all p < 0.05). CONCLUSION: Progression occurred in 56.7% of ASyS-ILD patients presenting with non-fibrotic patterns. Fibrotic patterns tended to persist. Age and radiographic progression were associated with reduced survival while the initial presence of GGO and predominant lower lobe distribution were associated with increased survival. KEY POINTS: • In ASyS-ILD, initial non-fibrotic patterns such as OP, cNSIP, or OP-cNSIP tended to progress to fNSIP. • Fibrotic patterns such as fNSIP or UIP in ASyS-ILD tended to persist without pattern changes. • GGO and lower lung predominance on initial CT were associated with better survival while advanced baseline age and radiographic ILD progression during follow-up were associated with decreased survival.


Subject(s)
Lung Diseases, Interstitial , Humans , Retrospective Studies , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/diagnostic imaging , Lung/diagnostic imaging , Fibrosis , Disease Progression
6.
Clin Rheumatol ; 40(10): 4089-4094, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33884496

ABSTRACT

Sporadic inclusion body myositis (sIBM) has been reported to occur in association with autoimmune diseases and in particular, primary Sjogren's syndrome (pSS). This brief report describes patients identified with a positive SSA antibody and diagnosis of sIBM at a large academic medical center over a 13.5-year period. A cohort identification tool was used to identify patients with positive SSA antibody and a diagnosis of sIBM between January 1, 2006 and June 1, 2019. All cases of sIBM had diagnostic confirmation by a neuromuscular specialist. Demographics, clinical features, autoantibodies, MRI and EMG findings, and muscle biopsy features were reviewed for each identified case. Eight patients were found to carry the diagnosis of pSS and sIBM. Two additional sIBM patients were SSA antibody positive without other pSS features. The mean time from initial symptom onset of muscle weakness to diagnosis was 5.4 years (range 1-15 years). All patients had alternative diagnoses offered for their myopathic symptoms prior to sIBM identification. The NT5c1A antibody was positive in 7 of 8 patients tested. No patient had a durable response to immunosuppressive therapy. The diagnosis of sIBM went unrecognized for over 5 years in our cohort of SSA antibody-positive patients with myopathy. The patients in this cohort were treated with a variety of immunosuppressive agents prior to diagnosis without benefit. Recognizing the clinical features of sIBM in patients with pSS is crucial in instituting appropriate therapy and avoiding unnecessary immunosuppression. Key Points • Sporadic inclusion body myositis (sIBM) can be associated with Sjogren's syndrome. • In this case series, prevalence of the NT5c1A antibody was higher among patients with associated Sjogren's syndrome compared to the cited prevalence of the NT5c1A antibody in patients with isolated sIBM. • It is crucial to consider sIBM in patients with Sjogren's syndrome presenting with motor weakness in order to avoid unnecessary immunosuppression and institute appropriate therapy.


Subject(s)
Autoimmune Diseases , Myositis, Inclusion Body , Sjogren's Syndrome , Autoantibodies , Cohort Studies , Humans , Sjogren's Syndrome/complications , Sjogren's Syndrome/diagnosis
8.
Curr Rheumatol Rep ; 22(8): 40, 2020 06 19.
Article in English | MEDLINE | ID: mdl-32562020

ABSTRACT

PURPOSE OF THE REVIEW: Polymyalgia rheumatica (PMR) is one of the most common inflammatory rheumatologic condition occurring in older adults. It is characterized by proximal pain and stiffness in the shoulders, neck, and/or pelvic girdle in individuals over 50 years of age along with evidence of an intense systemic inflammatory response. Although the above clinical symptoms are very characteristic for the condition, it can be mimicked by other autoimmune, infectious, malignant, and endocrine disorders chief among which are giant cell arteritis (GCA) and elderly-onset rheumatoid arthritis (EORA). Recently, PMR was reported in relation to treatment with immune checkpoint inhibitors. Current treatment of PMR consists of low-to-medium doses of glucocorticosteroids (GC) with variable response rates and disease recurrence estimated to occur in 50% of patients while tapering down GC doses. In addition, GC-based regimens cause much of the morbidity associated with PMR in older adults, requiring close monitoring for GC-induced toxicity during therapy and highlighting the need for novel therapeutic strategies. Here, we review the latest findings in the field regarding specific etiologic factors, genetic associations, diagnostic methods, and advancements in treatment strategies and disease monitoring indices. RECENT FINDINGS: Recent discoveries involving novel therapeutic targets in GCA have accelerated the study of PMR pathophysiology and have advanced treatment strategies in PMR management leading to current trials in IL-6 blocking agents. PMR remains an enigmatic inflammatory condition affecting older adults, with current treatment approach causing much morbidity in this patient population. Advancements in our understanding of novel immunopathologic targets can serve as a solid foundation for future treatment strategies in the field.


Subject(s)
Arthritis, Rheumatoid , Giant Cell Arteritis , Polymyalgia Rheumatica , Aged , Giant Cell Arteritis/diagnosis , Giant Cell Arteritis/drug therapy , Giant Cell Arteritis/epidemiology , Glucocorticoids/therapeutic use , Humans , Polymyalgia Rheumatica/diagnosis , Polymyalgia Rheumatica/drug therapy , Polymyalgia Rheumatica/epidemiology
9.
J Pediatr Surg ; 55(7): 1405-1408, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32234319

ABSTRACT

PURPOSE: Extracorporeal membrane oxygenation (ECMO) supports gas exchange and circulation in critically ill patients. This study describes a multidisciplinary approach to ECMO cannulation using the expertise of pediatric surgery (PS) and interventional radiology (IR). MATERIAL AND METHODS: Pediatric patients (<18 years) undergoing percutaneous cannulation for peripheral veno-arterial (VA) ECMO by PS and IR from April 2017 to May 2018 were included. Cardiac patients and children cannulated by PS alone were excluded. RESULTS: Five patients were included in the series. Median age was 16 [12.5-17] years and 3 were female. Median ECMO arterial and venous catheter sizes were 19 [17-22] Fr and 25 [25-28] Fr, respectively. Both catheters were placed in the common femoral vessels. A 6Fr antegrade distal perfusion cannula (DPC) was also placed in the superficial femoral artery by IR at the time of cannulation. The median time from admission to procedure start was 10 [7-50] hours and the children were on ECMO for a median length of 3.2 [2.3-4.8] days. There were two episodes of bleeding. No patients had loss of limb circulation. CONCLUSION: A multidisciplinary approach to peripheral VA ECMO cannulation is feasible and safe. Maintenance of limb perfusion by percutaneous placement and removal of DPC may be an advantage of this collaborative approach. LEVEL OF EVIDENCE: IV. TYPE OF RESEARCH: Case series.


Subject(s)
Catheterization, Peripheral/methods , Extracorporeal Membrane Oxygenation/methods , Femoral Artery/surgery , Adolescent , Catheterization, Peripheral/statistics & numerical data , Child , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Humans , Male
10.
J Vasc Interv Radiol ; 31(1): 93-98, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31767410

ABSTRACT

PURPOSE: To determine the diagnostic yield and safety of image-guided lung biopsies in immunocompromised pediatric patients. MATERIALS AND METHODS: This was a retrospective pediatric cohort study conducted from June 2000 to April 2017. Subjects were 0-17 years of age (median, 10 years of age). There were 46 males (48%). A total of 73 consecutive image-guided lung biopsies were performed in 68 patients (weight range, 4.9-97.3 kg [median, 25.3 kg]). The indication for biopsy was to isolate an organism to tailor medical therapy. All patients were immunocompromised with an underlying history of bone marrow transplantation (n = 50), primary immunodeficiency (n = 14), and solid organ transplantation (n = 4). Patient and technical factors were analyzed for rates of complication. RESULTS: Overall diagnostic yield was 43 of 73 patients (60%). There were 14 minor (19%) and 8 major (11%) complications. Major complications included pneumothorax or hemoptysis requiring intervention (n = 6), and death (n = 2). The histological diagnosis was an infectious cause in 5 of 8 major complications (63%). There were statistically significant differences between the rates of complications with the imaging modality used (P = .02) and the use of fine needle aspiration (P = .02). CONCLUSIONS: Image-guided percutaneous lung biopsy can be helpful in isolating an organism to tailor therapy. Biopsies performed in immunosuppressed patients result in an elevated complication risk of up to 30% and demonstrate lower diagnostic yield and increased mortality, which should warrant detailed discussion with the primary team and family.


Subject(s)
Image-Guided Biopsy , Immunocompromised Host , Lung Diseases/pathology , Lung/pathology , Radiography, Interventional , Ultrasonography, Interventional , Adolescent , Age Factors , Biopsy, Fine-Needle , Child , Child, Preschool , Female , Humans , Image-Guided Biopsy/adverse effects , Image-Guided Biopsy/mortality , Infant , Infant, Newborn , Lung/immunology , Lung Diseases/immunology , Lung Diseases/mortality , Male , Patient Safety , Predictive Value of Tests , Prognosis , Radiography, Interventional/adverse effects , Radiography, Interventional/mortality , Retrospective Studies , Risk Assessment , Risk Factors , Ultrasonography, Interventional/adverse effects , Ultrasonography, Interventional/mortality
11.
Front Neurosci ; 13: 798, 2019.
Article in English | MEDLINE | ID: mdl-31447629

ABSTRACT

Testosterone can be safely and effectively administered to estrogen-treated post-menopausal women experiencing hypoactive sexual desire. However, in the United States and Canada, although it is often administered off-label, testosterone co-administered with estradiol is not a federally approved treatment for sexual arousal/desire disorder, partly because its mechanism is poorly understood. One possible mechanism involves the aromatization of testosterone to estradiol. In an animal model, the administration of testosterone propionate (TP) given in combination with estradiol benzoate (EB) significantly increases sexually appetitive behaviors (i.e., solicitations and hops/darts) in ovariectomized (OVX) Long-Evans rats, compared to those treated with EB-alone. The goal of current study was to test whether blocking aromatization of testosterone to estradiol would disrupt the facilitation of sexual behaviors in OVX Long-Evans rats, and to determine group differences in Fos immunoreactivity within brain regions involved in sexual motivation and reward. Groups of sexually experienced OVX Long-Evans rats were treated with EB alone, EB+TP, or EB+TP and the aromatase inhibitor Fadrozole (EB+TP+FAD). Females treated with EB+TP+FAD displayed significantly more hops and darts, solicitations and lordosis magnitudes when compared to EB-alone females. Furthermore, TP, administered with or without FAD, induced the activation of Fos-immunoreactivity in brain areas implicated in sexual motivation and reward including the medial preoptic area, ventrolateral division of the ventromedial nucleus of the hypothalamus, the nucleus accumbens core, and the prefrontal cortex. These results suggest that aromatization may not be necessary for TP to enhance female sexual behavior and that EB+TP may act via androgenic pathways to increase the sensitivity of response to male-related cues, to induce female sexual desire.

12.
J Rheumatol ; 46(10): 1345-1349, 2019 10.
Article in English | MEDLINE | ID: mdl-30647192

ABSTRACT

OBJECTIVE: In this retrospective observational study, we assess the efficacy and safety of the interleukin 1 receptor antagonist anakinra in medically complex, hospitalized patients with acute gout and calcium pyrophosphate crystal arthritis. METHODS: Adult inpatients treated with anakinra from 2014 to 2017 were identified for inclusion. Charts were reviewed for demographics, comorbidities, laboratory data, pain scores, joint involvement, prior treatment, dosing and response to anakinra, concurrent infections, and surgical interventions. Response to anakinra treatment was determined from review of provider documentation, as well as recorded pain scores on a numeric scale. RESULTS: We identified 100 individuals accounting for 115 episodes of arthritis. This population was 82% male, with an average age of 60 years. Comorbidities included renal disease (45%) and history of organ transplantation (14%). Twenty-nine episodes of arthritis occurred in the perioperative setting. Concurrent infection was present in 34 episodes. Eighty-six episodes of arthritis had partial or complete response to anakinra within 4 days of treatment initiation; 66 episodes had partial or complete response within 1 day of anakinra administration. Anakinra was well tolerated. CONCLUSION: To our knowledge, this is the largest observational study of anakinra use in the inpatient setting for the acute treatment of crystal-associated arthritis. We observed a rapid response to anakinra, with 75% of episodes significantly improving or completely resolving within 4 days of the first dose. Our data also support the use of this biologic agent in individuals with infections, as well as perioperative individuals and immunosuppressed transplant recipients.


Subject(s)
Antirheumatic Agents/therapeutic use , Gout/drug therapy , Hospitalization , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Acute Disease , Aged , Antirheumatic Agents/adverse effects , Comorbidity , Female , Humans , Interleukin 1 Receptor Antagonist Protein/adverse effects , Male , Middle Aged , Retrospective Studies , Treatment Outcome
13.
Neuropsychopharmacology ; 44(7): 1274-1283, 2019 06.
Article in English | MEDLINE | ID: mdl-30647449

ABSTRACT

Nestled within feeding circuits, the oval (ov) region of the Bed Nucleus of the Stria Terminalis (BNST) may be critical for monitoring energy balance through changes in synaptic strength. Here we report that bidirectional plasticity at ovBNST GABA synapses was tightly linked to the caloric state of male rats, seesawing between long-term potentiation (iLTP, fed) and depression (iLTD, food restricted). L-α-lysophosphatidylinositol (LPI) acting on GPR55 receptors and 2-arachidonoylglycerol (2-AG) through CB1R were respectively responsible for fed (iLTP) and food restricted (iLTD) states. Thus, we have characterized a potential gating mechanism within the ovBNST that may signal metabolic state within the rat brain feeding circuitry.


Subject(s)
Neuronal Plasticity , Receptors, Cannabinoid/physiology , Receptors, G-Protein-Coupled/physiology , Satiety Response/physiology , Septal Nuclei/physiology , Animals , Gene Knockout Techniques , Inhibitory Postsynaptic Potentials , Male , Mice, Inbred C57BL , Rats, Long-Evans , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/physiology , Receptors, Cannabinoid/genetics , Receptors, G-Protein-Coupled/genetics , Synapses/physiology , gamma-Aminobutyric Acid/physiology
14.
JACC Clin Electrophysiol ; 4(1): 49-58, 2018 01.
Article in English | MEDLINE | ID: mdl-29600786

ABSTRACT

OBJECTIVES: The purpose of this study is to evaluate the spatial distribution of late gadolinium enhancement (LGE) of the left atrium (LA) by LGE-magnetic resonance imaging in an atrial fibrillation (AF) population. BACKGROUND: LGE of the LA can be a surrogate of pre-existing structural remodeling of LA. METHODS: LGE-magnetic resonance imaging scans were used for 160 patients with AF (mean age 66 ± 11 years) before AF ablation. To know the spatial distribution of LGE, the extent of LGE in 6 LA subregions was examined. Overall LGE distribution was also summarized as a spatial frequency histogram using an atlas of LA shape. These data were also compared between paroxysmal AF (87 patients) and persistent AF (73 patients). RESULTS: LGE coverage (%) in each subregion was as follows: 41.8 ± 18.9% in the left pulmonary vein (PV) antrum, 27.1 ± 16.7% in the left lateral wall, 25.8 ± 15.3% in the posterior wall, 19.7 ± 15.3% in the anterior wall, 17.1 ± 15.0% in the right PV antrum, and 12.0 ± 13.2% in the septum wall. LGE was heterogeneously distributed in the LA and was found with the highest frequency in the posterior wall near the inferior left PV antrum by the LGE histogram. A comparison of paroxysmal AF with persistent AF suggests that LGE was more expected in persistent AF compared with paroxysmal AF, particularly with a spread on the posterior and the anterior wall. CONCLUSIONS: LGE in the LA was heterogeneously distributed. LGE was highly distributed in the inferior left PV antrum near the posterior wall side, and spread on the posterior and anterior wall with AF progression.


Subject(s)
Atrial Fibrillation , Contrast Media/pharmacokinetics , Gadolinium/pharmacokinetics , Heart Atria , Magnetic Resonance Imaging/methods , Aged , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/metabolism , Atrial Remodeling , Contrast Media/administration & dosage , Contrast Media/therapeutic use , Female , Gadolinium/administration & dosage , Gadolinium/therapeutic use , Heart Atria/diagnostic imaging , Heart Atria/metabolism , Humans , Image Interpretation, Computer-Assisted , Imaging, Three-Dimensional , Male , Middle Aged , Tissue Distribution
15.
Med Clin North Am ; 100(4): 719-31, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27235612

ABSTRACT

Disease-modifying antirheumatic drugs (DMARDs) are commonly prescribed by rheumatologists to reduce disease activity and induce remission in autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis. Steroids are sometimes used in combination with DMARD therapy and should be used at the lowest effective dose for the least amount of time. There are many biologic agents available for use for inflammatory arthritis and other autoimmune conditions. Care should be taken when prescribing and managing DMARDS, steroids and biologic agents medications with a careful eye towards screening for infectious disease, vaccination, bone heath and lab monitoring.


Subject(s)
Antirheumatic Agents/therapeutic use , Autoimmune Diseases/drug therapy , Biological Products/therapeutic use , Immunosuppressive Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Biological Products/administration & dosage , Biological Products/adverse effects , Colchicine/therapeutic use , Gout Suppressants/therapeutic use , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Methotrexate/therapeutic use
16.
JACC Clin Electrophysiol ; 2(6): 711-719, 2016 Nov.
Article in English | MEDLINE | ID: mdl-29759749

ABSTRACT

OBJECTIVES: This study hypothesized that left atrial structural remodeling (LA-TR) correlates with exercise capacity (EC) in a cohort of patients with atrial fibrillation (AF). BACKGROUND: Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging provides a method of assessing LA-TR in patients with AF. METHODS: A total of 145 patients (32% female, mean age 63.4 ± 11.6 years of age) with AF (66 paroxysmal, 71 persistent, 8 long-standing persistent) presenting for catheter ablation were included in the study. All patients underwent LGE-CMR imaging as well as maximal exercise test using the Bruce protocol prior to catheter ablation of AF. EC was quantified by minutes of exercise and metabolic equivalent (MET) level achieved. LA-TR was quantified from LGE-CMR imaging and classified according to the Utah classification of LA structural remodeling (Utah stage I: <10% LA wall enhancement; Utah II: 10% to <20%; Utah III: 20% to <30%; and Utah IV: >30%). AF recurrence was assessed at 1 year from the date of ablation. RESULTS: The average duration of exercise was 8 ± 3 min, and the mean MET achieved was 9.7 ± 3.2. METs achieved were inversely correlated with LA-TR (R2 = 0.061; p = 0.003). The duration of exercise was also inversely correlated with LA-TR (R2 = 0.071; p = 0.001). Both EC and LA-TR were associated with AF recurrence post ablation in univariate analysis, but only LA-TR and age were independently predictive of recurrence in multivariate analysis (p = 0.001). For every additional minute on the treadmill, subjects were 13% more likely to be free of AF 1 year post ablation (p = 0.047). CONCLUSIONS: EC is inversely associated with LA-TR in patients with AF and is predictive of freedom from AF post-ablation.

17.
Eur J Neurosci ; 42(12): 3138-48, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26536143

ABSTRACT

Dopamine (DA) transmission in the medial preoptic area (mPOA) plays a critical role in the control of appetitive sexual behaviour in the female rat. We have shown previously that a DA D1 receptor (D1R)-mediated excitatory state appears to occur in females primed with estradiol benzoate (EB) and progesterone (P), whereas a DA D2 receptor (D2R)-mediated inhibitory state appears to occur in females primed only with EB. The present experiment employed three techniques to better understand what changes occur to DA receptors (DARs) in the mPOA under different hormonal profiles. Ovariectomized females were randomly assigned to one of three steroid treatment groups: EB + P (10 and 500 µg, respectively), EB + Oil, or the control (Oil + Oil), with hormone injections administered at 48 and 4 h prior to euthanizing. First, the number of neurons in the mPOA that contained D1R or D2R was assessed using immunohistochemistry. Second, the mPOA and two control areas (the prelimbic cortex and caudate putamen) were analysed for DAR protein levels using western blot, and DAR functional binding levels using autoradiography. Ovarian steroid hormones affected the two DAR subtypes in opposite ways in the mPOA. All three techniques supported previous behavioural findings that females primed with EB have a lower D1R : D2R ratio, and thus a D2R-mediated system, and females primed with EB + P have a higher D1R : D2R ratio, and thus a D1R-mediated system. This provides strong evidence for a DA-driven pathway of female sexual motivation, desire, and behaviour that is modified by different hormone priming regimens.


Subject(s)
Estradiol/analogs & derivatives , Preoptic Area/metabolism , Progesterone/metabolism , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/metabolism , Sexual Behavior, Animal/physiology , Animals , Caudate Nucleus/cytology , Caudate Nucleus/drug effects , Caudate Nucleus/metabolism , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Estradiol/administration & dosage , Estradiol/metabolism , Estrogens/administration & dosage , Female , Motivation/drug effects , Motivation/physiology , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Ovariectomy , Posture/physiology , Preoptic Area/cytology , Preoptic Area/drug effects , Progesterone/administration & dosage , Progestins/administration & dosage , Putamen/cytology , Putamen/drug effects , Putamen/metabolism , Random Allocation , Rats, Long-Evans , Sexual Behavior, Animal/drug effects
18.
Horm Behav ; 75: 70-7, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26278846

ABSTRACT

The acute administration of estradiol benzoate (EB) to the ovariectomized (OVX) rat induces low levels of lordosis while sexually appetitive behaviors (e.g., hops, darts, solicitations) are absent, yet the repeated administration of EB results in a behavioral sensitization in which lordosis is potentiated and sexually appetitive behaviors are induced. We have shown that repeated copulation attenuates the sensitization of appetitive sexual behaviors. Here, we assessed which component of male stimulation during copulation is involved in the attenuation. On 8 occasions, sexually experienced OVX Long-Evans rats were treated with 10µgEB and 48h later assigned to one of six groups that differed in their experience on intermediates tests (2-7). One was given repeated access to a male (EB/Male), and another was placed in the copulation chamber alone (EB/Alone) on intermediate tests. Three groups were given one of three somatosensory stimuli by the experimenter: manual flank stimulation (FLS), clitoral stimulation (CLS), or vaginocervical stimulation (VCS). Finally, the control group was left undisturbed in the animal care facility (ACF). Sexual behaviors were measured on Tests 1 and 8. VCS received from the experimenter (VCS) or from the male during copulation (EB/Male) attenuated the magnitude of the sensitization of appetitive sexual behaviors compared with those that were not brought to the testing rooms (ACF), and the effect was most pronounced on sexual solicitations. These results suggest that VCS received during penile intromission inhibits the sensitization of sexually appetitive behaviors by repeated administration of EB. As such, repeated administration of EB may oppose those mechanisms that induce estrous termination, perhaps by sensitizing inhibitory processes within the ventromedial hypothalamus that typically prevent the display of sexual behaviors (i.e., by facilitating disinhibition).


Subject(s)
Appetitive Behavior/physiology , Copulation/physiology , Estradiol/analogs & derivatives , Physical Stimulation , Sexual Behavior, Animal/drug effects , Animals , Appetitive Behavior/drug effects , Cervix Uteri , Copulation/drug effects , Estradiol/pharmacology , Estrus/drug effects , Female , Male , Ovariectomy , Posture/physiology , Rats , Rats, Long-Evans , Sexual Behavior, Animal/physiology , Vagina
19.
Psychopharmacology (Berl) ; 232(20): 3773-82, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26246318

ABSTRACT

RATIONALE: Food restriction augments heroin seeking in chronically food-restricted male rats under withdrawal, an effect not yet examined in female rats. Importantly, women and female rats possess an increased vulnerability to drugs of abuse, which may be mediated by fluctuations in ovarian hormones. OBJECTIVES: We investigated the role of estradiol and progesterone in augmented heroin seeking in chronically food-restricted female rats, under withdrawal. METHODS: Female rats self-administered heroin for 10-12 days and were then allowed unrestricted (sated) or restricted access to food (FDR; ∼10 % reduction in body weight) for 14 days. On day 14, rats underwent a heroin-seeking test. Exp. 1: Rats underwent ovariectomy or sham surgery and were treated with a low dose of estradiol (5.0 % in cholesterol; subcutaneous capsule). Exp. 2: Rats underwent ovariectomy and were administered with a high dose of estradiol (0.5 mg/kg; subcutaneous) for 8 days before testing. Exp. 3: Progesterone injections (2.0 mg/kg; subcutaneous) were administered 24 h and 2 h before testing. RESULTS: Food restriction resulted in augmented heroin seeking, compared to sated controls. While ovariectomy had no effect, estradiol replacement attenuated the food restriction effect. Injections of progesterone had no effect on heroin seeking in either the sated or FDR groups. CONCLUSIONS: The effect of food restriction on heroin seeking in female rats under withdrawal is as robust as previously found in males. Interestingly, estradiol replacement, but not progesterone, attenuates the food restriction effect in the ovariectomized rats, possibly due to its anorexic properties.


Subject(s)
Estradiol/blood , Food Deprivation/physiology , Heroin Dependence/blood , Heroin/administration & dosage , Ovary/metabolism , Progesterone/blood , Animals , Estradiol/administration & dosage , Female , Heroin Dependence/psychology , Ovariectomy , Ovary/drug effects , Progesterone/administration & dosage , Rats , Self Administration
20.
Horm Behav ; 75: 1-10, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26210062

ABSTRACT

An acute injection of estradiol benzoate (EB) to the ovariectomized (OVX) rat activates low levels of lordosis, and subsequent progesterone (P) administration augments lordosis and recruits a complete pattern of sexual behavior including appetitive behaviors (e.g., hops/darts and solicitations). However, repeated injections of 5µg or 10µg EB (but not 2µg EB), administered every 4days to sexually-experienced OVX rats results in a behavioral sensitization, such that lordosis quotients (LQs) and appetitive behaviors progressively increase. We have shown that adrenal P does not play a critical role because behavioral sensitization to EB is not prevented by adrenalectomy. Here we tested whether P receptors play a role by examining the effect of chronic administration of the P receptor antagonist RU486 at a dose that reliably inhibits sexual behavior in fully primed OVX rats. Females were treated with EB (5 or 10µg), and 5mg RU486 dissolved in 0.4mL vehicle (VEH; 80% sesame oil, 15% benzyl benzoate, 5% benzyl alcohol) 48h and 5h prior to each of 7 tests, respectively, occurring at 4-day intervals in unilevel 4-hole pacing chambers. Control animals were treated with 2, 5, or 10µg EB+VEH. As expected, sensitization did not occur in females treated with 2µg EB+VEH, and those females received fewer intromissions and ejaculations than all other groups. RU486 did not prevent the sensitization of LQ, moderate and high lordosis magnitudes (LM2 and LM3) or appetitive sexual behaviors on early tests, and in fact potentiated appetitive behaviors, LQ, LM2 and LM3, consistent with its facilitative actions in females treated with EB-alone, as we and others have reported previously. However, despite the initial facilitation, blocking P receptors by chronic administration of RU486 inhibited the maintenance of behavioral sensitization to EB.


Subject(s)
Estradiol/analogs & derivatives , Mifepristone/pharmacology , Sexual Behavior, Animal/drug effects , Animals , Appetitive Behavior/drug effects , Ejaculation/drug effects , Estradiol/pharmacology , Female , Humans , Male , Ovariectomy , Posture , Progesterone/pharmacology , Rats , Rats, Long-Evans , Receptors, Progesterone/metabolism , Sexual Behavior, Animal/physiology , Time Factors
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