Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
1.
Sci Rep ; 11(1): 57, 2021 01 08.
Article in English | MEDLINE | ID: mdl-33420230

ABSTRACT

The inner ear, or cochlea, is a fluid-filled organ housing the mechanosensitive hair cells. Sound stimulation is relayed to the hair cells through waves that propagate on the elastic basilar membrane. Sensorineural hearing loss occurs from damage to the hair cells and cannot currently be cured. Although drugs have been proposed to prevent damage or restore functionality to hair cells, a difficulty with such treatments is ensuring adequate drug delivery to the cells. Because the cochlea is encased in the temporal bone, it can only be accessed from its basal end. However, the hair cells that are responsible for detecting speech-frequency sounds reside at the opposite, apical end. In this paper we show that steady streaming can be used to transport drugs along the cochlea. Steady streaming is a nonlinear process that accompanies many fluctuating fluid motions, including the sound-evoked waves in the inner ear. We combine an analytical approximation for the waves in the cochlea with computational fluid dynamic simulations to demonstrate that the combined steady streaming effects of several different frequencies can transport drugs from the base of the cochlea further towards the apex. Our results therefore show that multi-frequency sound stimulation can serve as a non-invasive method to transport drugs efficiently along the cochlea.


Subject(s)
Ear, Inner , Instillation, Drug , Cochlea , Drug Delivery Systems/methods , Humans , Hydrodynamics
2.
Cancer Prev Res (Phila) ; 13(9): 747-760, 2020 09.
Article in English | MEDLINE | ID: mdl-32518084

ABSTRACT

Psychological stressors have been implicated in the progression of various tumor types. We investigated a role for stress in tumor immune cell chemotaxis in the B16F10 mouse model of malignant melanoma. We exposed female mice to 6-hour periods of restraint stress (RST) for 7 days, then implanted B16F10 malignant melanoma tumor cells and continued the RST paradigm for 14 additional days. We determined serum corticosterone and liver catecholamine concentrations in these mice. To evaluate the tumor microenvironment, we performed IHC and examined cytokine expression profiles using ELISA-based analysis of tumor homogenates. We found that tumors in mice subjected to RST grew significantly slower, had reduced tumor C-C motif ligand 2 (CCL2), and contained fewer F4/80-positive macrophages than tumors from unstressed mice. We observed a concomitant increase in norepinephrine among the RST mice. An in vitro assay confirmed that norepinephrine downregulates CCL2 production in both mouse and human macrophages, and that pretreatment with the pan-ß-adrenergic receptor inhibitor nadolol rescues this activity. Furthermore, RST had no effect on tumor growth in transgenic CCL2-deficient mice. This study suggests that stress reduces malignant melanoma by reducing recruitment of tumor-promoting macrophages by CCL2.


Subject(s)
Chemokine CCL2/genetics , Melanoma, Experimental/immunology , Norepinephrine/metabolism , Skin Neoplasms/immunology , Stress, Psychological/immunology , Adrenergic beta-Antagonists/pharmacology , Animals , Cell Line, Tumor/transplantation , Down-Regulation/immunology , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/immunology , Humans , Macrophages/immunology , Macrophages/metabolism , Melanoma, Experimental/genetics , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Mice, Transgenic , Nadolol/pharmacology , Norepinephrine/antagonists & inhibitors , Restraint, Physical , Skin Neoplasms/genetics , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Stress, Psychological/metabolism , Tumor Microenvironment/drug effects , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology
3.
Phys Rev Lett ; 122(8): 085301, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30932601

ABSTRACT

In superfluid ^{3}He-B confined in a slab geometry, domain walls between regions of different order parameter orientation are predicted to be energetically stable. Formation of the spatially modulated superfluid stripe phase has been proposed. We confined ^{3}He in a 1.1 µm high microfluidic cavity and cooled it into the B phase at low pressure, where the stripe phase is predicted. We measured the surface-induced order parameter distortion with NMR, sensitive to the formation of domains. The results rule out the stripe phase, but are consistent with 2D modulated superfluid order.

4.
J Immunol ; 189(6): 3168-77, 2012 Sep 15.
Article in English | MEDLINE | ID: mdl-22869907

ABSTRACT

Macrophage secretion of vascular endothelial growth factor (VEGF) in response to hypoxia contributes to tumor growth and angiogenesis. In addition to VEGF, hypoxic macrophages stimulated with GM-CSF secrete high levels of a soluble form of the VEGF receptor (sVEGFR-1), which neutralizes VEGF and inhibits its biological activity. Using mice with a monocyte/macrophage-selective deletion of hypoxia-inducible factor (HIF)-1α or HIF-2α, we recently demonstrated that the antitumor response to GM-CSF was dependent on HIF-2α-driven sVEGFR-1 production by tumor-associated macrophages, whereas HIF-1α specifically regulated VEGF production. We therefore hypothesized that chemical stabilization of HIF-2α using an inhibitor of prolyl hydroxylase domain 3 (an upstream inhibitor of HIF-2α activation) would increase sVEGFR-1 production from GM-CSF-stimulated macrophages. Treatment of macrophages with the prolyl hydroxylase domain 3 inhibitor AKB-6899 stabilized HIF-2α and increased sVEGFR-1 production from GM-CSF-treated macrophages, with no effect on HIF-1α accumulation or VEGF production. Treatment of B16F10 melanoma-bearing mice with GM-CSF and AKB-6899 significantly reduced tumor growth compared with either drug alone. Increased levels of sVEGFR-1 mRNA, but not VEGF mRNA, were detected within the tumors of GM-CSF- and AKB-6899-treated mice, correlating with decreased tumor vascularity. Finally, the antitumor and antiangiogenic effects of AKB-6899 were abrogated when mice were simultaneously treated with a sVEGFR-1 neutralizing Ab. These results demonstrate that AKB-6899 decreases tumor growth and angiogenesis in response to GM-CSF by increasing sVEGFR-1 production from tumor-associated macrophages. Specific activation of HIF-2α can therefore decrease tumor growth and angiogenesis.


Subject(s)
Antineoplastic Agents/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Growth Inhibitors/metabolism , Macrophages/immunology , Macrophages/metabolism , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Vascular Endothelial Growth Factor Receptor-1/biosynthesis , Animals , Antineoplastic Agents/therapeutic use , Basic Helix-Loop-Helix Transcription Factors/physiology , Cell Line, Tumor , Cells, Cultured , Dioxygenases/antagonists & inhibitors , Dioxygenases/biosynthesis , Disease Models, Animal , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Growth Inhibitors/biosynthesis , Growth Inhibitors/therapeutic use , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases , Macrophages/pathology , Melanoma, Experimental/prevention & control , Mice , Mice, Inbred C57BL , Mice, SCID , Mice, Transgenic , Neovascularization, Pathologic/immunology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/prevention & control , Protein Stability , Solubility
5.
J Nurses Staff Dev ; 28(2): E5-9, 2012.
Article in English | MEDLINE | ID: mdl-22449890

ABSTRACT

The purpose of this descriptive study was to evaluate knowledge retention over time and clinical application of basic arrhythmia knowledge following exposure to an orientation program. Data showed significant differences in knowledge retention at 4 weeks and clinical application in rhythm identification using simulation at 3 months.


Subject(s)
Arrhythmias, Cardiac/nursing , Clinical Competence/standards , Nursing Evaluation Research , Arrhythmias, Cardiac/diagnosis , Education, Nursing, Continuing , Educational Measurement/methods , Educational Status , Female , Health Knowledge, Attitudes, Practice , Humans , Learning , Male , Program Development , Staff Development , Teaching/methods , United States
6.
J Immunol ; 187(4): 1970-6, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21765015

ABSTRACT

Macrophage secretion of vascular endothelial growth factor (VEGF) in response to the hypoxic tumor microenvironment contributes to tumor growth, angiogenesis, and metastasis. We have recently demonstrated that macrophages stimulated with GM-CSF at low O(2) secrete high levels of a soluble form of the VEGF receptor 1 (sVEGFR-1), which neutralizes VEGF and inhibits its biological activity. Using small interfering RNA targeting to deplete hypoxia-inducible factor (HIF)-1α or HIF-2α in murine macrophages, we found that macrophage production of sVEGFR-1 in response to low O(2) was dependent on HIF-2α, whereas HIF-1α specifically regulated VEGF production. In our current report, we evaluated the growth of B16F10 malignant melanoma in mice with a monocyte/macrophage-selective deletion of HIF-1α or HIF-2α (HIF-1α(flox/flox)- or HIF-2α(flox/+)/LysMcre mice). GM-CSF treatment increased intratumoral VEGF and sVEGFR-1 in control mice, an effect that was associated with a decrease in microvessel density. GM-CSF treatment of HIF-1α(flox/flox)/LysMcre mice induced sVEGFR-1 but not VEGF, resulting in an overall greater reduction in tumor growth and angiogenesis compared with control mice. In addition, real-time PCR for melanoma-specific genes revealed a significantly reduced presence of lung micrometastases in HIF-1α(flox/flox)/LysMcre mice treated with GM-CSF. Conversely, GM-CSF treatment induced VEGF but not sVEGFR-1 in HIF-2α(flox/+)/LysMcre mice, and, correspondingly, GM-CSF did not decrease tumor growth, angiogenesis, or lung metastasis in these mice. This study reveals opposing roles for the HIFs in the regulation of angiogenesis by tumor-associated macrophages and suggests that administration of GM-CSF might be an effective means of inducing sVEGFR-1 and inhibiting tumor growth and angiogenesis in patients with melanoma.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Lung Neoplasms/immunology , Melanoma/immunology , Neoplasm Proteins/immunology , Neovascularization, Pathologic/immunology , Vascular Endothelial Growth Factor Receptor-1/immunology , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/immunology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Macrophages/immunology , Macrophages/metabolism , Macrophages/pathology , Melanoma/genetics , Melanoma/metabolism , Melanoma/pathology , Mice , Mice, Knockout , Neoplasm Metastasis , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Oxygen/immunology , Oxygen/metabolism , Oxygen Consumption/genetics , Oxygen Consumption/immunology , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/immunology , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-1/metabolism
7.
Psychosomatics ; 50(3): 218-26, 2009.
Article in English | MEDLINE | ID: mdl-19567760

ABSTRACT

BACKGROUND: Falls and delirium in general-hospital inpatients are related to increases in morbidity, mortality, and healthcare costs. Patients fall despite safeguards and programs to reduce falling. OBJECTIVE: The authors sought to determine the prevalence of diagnosed and undiagnosed delirium in patients who fell during their hospital stay. METHOD: The authors performed a retrospective electronic chart review of 252 patients who fell during their hospital stay. Falls were categorized by their severity (i.e., minor, moderate, and major). Demographic information, patient outcomes, and diagnostic criteria for delirium (per DSM-IV) were collected on the day of admission, the day of the fall, and the 2 days preceding the patient's fall. RESULTS: Falls in the general hospital were associated with delirium (both diagnosed and undiagnosed), advanced age, and specific surgical procedures. CONCLUSION: Improving the recognition of undiagnosed delirium may lead to sustainable and successful fall prevention programs. Detection of impairments in mental status can assist staff to create individualized patient care plans. Knowledge about which patients are at risk for injury from delirium and falls can lead to improvements in patient safety, functioning, and quality of life.


Subject(s)
Accidental Falls/statistics & numerical data , Delirium/epidemiology , Postoperative Complications/epidemiology , Accidental Falls/prevention & control , Age Factors , Aged , Aged, 80 and over , Cross-Sectional Studies , Delirium/diagnosis , Diagnosis, Differential , Female , Hospitals, General/statistics & numerical data , Humans , Injury Severity Score , Male , Massachusetts , Middle Aged , Postoperative Complications/diagnosis , Retrospective Studies , Risk Factors , Secondary Prevention , Wounds and Injuries/epidemiology , Wounds and Injuries/prevention & control
SELECTION OF CITATIONS
SEARCH DETAIL
...