Fluorescence dynamics of human epidermis (ex vivo) and skin (in vivo)

2003 ◽  
Author(s):  
Elena V. Salomatina ◽  
Alexander B. Pravdin
Keyword(s):  
Ex Vivo ◽  
Human Epidermis

scholarly journals Early Spatial and Temporal Events of Human T-Lymphotropic Virus Type 1 Spread following Blood-Borne Transmission in a Rabbit Model of Infection

2010 ◽  
Vol 84 (10) ◽  
pp. 5124-5130 ◽  
Author(s):  
Rashade A. H. Haynes ◽  
Bevin Zimmerman ◽  
Laurie Millward ◽  
Evan Ware ◽  
Christopher Premanandan ◽  
...  
Keyword(s):  
Virus Type ◽  
Ex Vivo ◽  
Rabbit Model ◽  
Virus Detection ◽  
Mononuclear Leukocytes ◽  
T Lymphotropic Virus ◽  
Viral Spread ◽  
Temporal Events

ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia/lymphoma (ATL) and is associated with a variety of lymphocyte-mediated disorders. HTLV-1 transmission occurs by transmission of infected cells via breast-feeding by infected mothers, sexual intercourse, and contaminated blood products. The route of exposure and early virus replication events are believed to be key determinants of virus-associated spread, antiviral immune responses, and ultimately disease outcomes. The lack of knowledge of early events of HTLV-1 spread following blood-borne transmission of the virus in vivo hinders a more complete understanding of the immunopathogenesis of HTLV-1 infections. Herein, we have used an established animal model of HTLV-1 infection to study early spatial and temporal events of the viral infection. Twelve-week-old rabbits were injected intravenously with cell-associated HTLV-1 (ACH-transformed R49). Blood and tissues were collected at defined intervals throughout the study to test the early spread of the infection. Antibody and hematologic responses were monitored throughout the infection. HTLV-1 intracellular Tax and soluble p19 matrix were tested from ex vivo cultured lymphocytes. Proviral copy numbers were measured by real-time PCR from blood and tissue mononuclear leukocytes. Our data indicate that intravenous infection with cell-associated HTLV-1 targets lymphocytes located in both primary lymphoid and gut-associated lymphoid compartments. A transient lymphocytosis that correlated with peak virus detection parameters was observed by 1 week postinfection before returning to baseline levels. Our data support emerging evidence that HTLV-1 promotes lymphocyte proliferation preceding early viral spread in lymphoid compartments to establish and maintain persistent infection.

scholarly journals Nanostructured Lipid Carrier Gel for the Dermal Application of Lidocaine: Comparison of Skin Penetration Testing Methods

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 310 ◽  
Author(s):  
Stella Zsikó ◽  
Kendra Cutcher ◽  
Anita Kovács ◽  
Mária Budai-Szűcs ◽  
Attila Gácsi ◽  
...  
Keyword(s):  
Drug Release ◽  
Human Skin ◽  
Ex Vivo ◽  
Study Drug ◽  
Skin Penetration ◽  
Human Epidermis ◽  
Nanostructured Lipid Carrier ◽  
Experimental Findings

The aim of this research was to investigate the stability of a lidocaine-loaded nanostructured lipid carrier dispersion at different temperatures, formulate a nanostructured lipid carrier gel, and test the penetration profile of lidocaine from the nanostructured lipid carrier gel using different skin penetration modeling methods. The formulations were characterized by laser diffraction, rheological measurements and microscopic examinations. Various in vitro methods were used to study drug release, diffusion and penetration. Two types of vertical Franz diffusion cells with three different membranes, including cellulose, Strat-M®, and heat separated human epidermis were used and compared to the Skin-parallel artificial membrane permeability assay (PAMPA) method. Results indicated that the nanostructured lipid carrier dispersion had to be gelified as soon as possible for proper stability. Both the Skin-PAMPA model and Strat-M® membranes correlated favorably with heat separated human epidermis in this research, with the Strat-M® membranes sharing the most similar drug permeability profile to an ex vivo human skin model. Our experimental findings suggest that even when the best available in vitro experiment is selected for modeling human skin penetration to study nanostructured lipid carrier gel systems, relevant in vitro/in vivo correlation should be made to calculate the drug release/permeation in vivo. Future investigations in this field are still needed to demonstrate the influence of membranes and equipment from other classes on other drug candidates.

scholarly journals PTH Modulation by Aldosterone and Angiotensin II is Blunted in Hyperaldosteronism and Rescued by Adrenalectomy

2019 ◽  
Vol 104 (9) ◽  
pp. 3726-3734 ◽  
Author(s):  
Livia Lenzini ◽  
Selene Prisco ◽  
Paul Emmanuel Vanderriele ◽  
Silvia Lerco ◽  
Francesca Torresan ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ex Vivo ◽  
Primary Cultures ◽  
Zona Glomerulosa ◽  
Before And After ◽  
Bilateral Adrenal Hyperplasia ◽  
Aldosterone Producing Adenoma ◽  
Serum Pth

Abstract Context Accumulating evidence suggests a link between adrenocortical zona glomerulosa and parathyroid gland through mechanisms that remain unexplored. Objectives To test the hypothesis that in vivo angiotensin II blockade affects PTH secretion in patients with hypertension and that aldosterone and angiotensim II directly stimulate PTH secretion ex vivo. Design and Setting We investigated the changes of serum PTH levels induced by oral captopril (50 mg) administration in patients with primary essential hypertension (EH) and with primary aldosteronism (PA) caused by bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenoma (APA), the latter before and after adrenalectomy. We also exposed primary cultures of human parathyroid cells from patients with primary hyperparathyroidism to angiotensin II (10−7 M) and/or aldosterone (10−7 M). Results Captopril lowered PTH levels (in nanograms per liter) both in patients with EH (n = 63; 25.9 ± 8.3 baseline vs 24.4 ± 8.0 postcaptopril, P < 0.0001) and in patients with APA after adrenalectomy (n = 27; 26.3 ± 11.6 vs 24.0 ± 9.7 P = 0.021). However, it was ineffective in patients with full-blown PA caused by APA and BAH. In primary culture of human parathyroid cells, both aldosterone (P < 0.001) and angiotensin II (P = 0.002) markedly increased PTH secretion from baseline, by acting through mineralocorticoid receptor and angiotensin type 1 receptor, as these effects were abolished by canrenone and irbesartan, respectively. Conclusion These results collectively suggest an implication of the renin-angiotensin-aldosterone system in PTH regulation in humans, at least in PTH-secreting cells obtained from parathyroid tumors. Moreover, they further support the concept that mild hyperparathyroidism is a feature of human PA that is correctable with adrenalectomy.

Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function

2009 ◽  
Vol 297 (6) ◽  
pp. H2096-H2108 ◽  
Author(s):  
Ratnadeep Basu ◽  
Gavin Y. Oudit ◽  
Xiuhua Wang ◽  
Liyan Zhang ◽  
John R. Ussher ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Ex Vivo ◽  
Systolic Function ◽  
Doppler Imaging ◽  
Hemodynamic Measurements ◽  
Long Chain

Diabetic cardiomyopathy is an important contributor to diastolic and systolic heart failure. We examined the nature and mechanism of the cardiomyopathy in Akita ( Ins2WT/C96Y) mice, a model of genetic nonobese type 1 diabetes that recapitulates human type 1 diabetes. Cardiac function was evaluated in male Ins2WT/C96Y and their littermate control ( Ins2WT/WT) mice using echocardiography and tissue Doppler imaging, in vivo hemodynamic measurements, as well as ex vivo working heart preparation. At 3 and 6 mo of age, Ins2WT/C96Y mice exhibited preserved cardiac systolic function compared with Ins2WT/WT mice, as evaluated by ejection fraction, fractional shortening, left ventricular (LV) end-systolic pressure and maximum rate of increase in LV pressure in vivo, cardiac work, cardiac power, and rate-pressure product ex vivo. Despite the unaltered systolic function, Ins2WT/C96Y mice exhibited significant and progressive diastolic dysfunction at 3 and 6 mo of age compared with Ins2WT/WT mice as assessed by tissue and pulse Doppler imaging (E-wave velocity, isovolumetric relaxation time) and by in vivo hemodynamic measurements (LV end-diastolic pressure, time constant of LV relaxation, and maximum rate of decrease in LV pressure). We found no evidence of myocardial hypertrophy or fibrosis in the Ins2WT/C96Y myocardium. Consistent with the lack of fibrosis, expression of procollagen-α type I, procollagen-α type III, and fibronectin were not increased in these hearts. Ins2WT/C96Y hearts showed significantly reduced sarcoplasmic reticulum Ca2+-ATPase 2a (cardiac sarcoplasmic reticulum Ca2+ pump) levels, elevated β-myosin heavy chain isoform, increased long-chain fatty acids, and triacylglycerol with evidence of lipotoxicity, as indicated by a significant rise in ceramide, diacylglycerol, and lipid deposits in the myocardium. Consistent with metabolic perturbation, and a switch to fatty acid oxidation from glucose oxidation in Ins2WT/C96Y hearts, expression of mitochondrial long-chain acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase isoform 4 were increased. Insulin treatment reversed the diastolic dysfunction, the elevated B-type natriuretic peptide and β-myosin heavy chain, and the reduced sarcoplasmic reticulum Ca2+-ATPase 2a levels with abolition of cardiac lipotoxicity. We conclude that early type 1 diabetic cardiomyopathy is characterized by diastolic dysfunction associated with lipotoxic cardiomyopathy with preserved systolic function in the absence of interstitial fibrosis and hypertrophy.

scholarly journals β-Cell Generation: Can Rodent Studies Be Translated to Humans?

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Françoise Carlotti ◽  
Arnaud Zaldumbide ◽  
Johanne H. Ellenbroek ◽  
H. Siebe Spijker ◽  
Rob C. Hoeben ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cell Mass ◽  
Cell Types ◽  
Organ Donors ◽  
Cell Replacement Therapy ◽  
Β Cell ◽  
Cell Replacement ◽  
Therapeutic Alternatives

β-cell replacement by allogeneic islet transplantation is a promising approach for patients with type 1 diabetes, but the shortage of organ donors requires new sources ofβcells. Islet regenerationin vivoand generation ofβ-cellsex vivofollowed by transplantation represent attractive therapeutic alternatives to restore theβ-cell mass. In this paper, we discuss different postnatal cell types that have been envisaged as potential sources for futureβ-cell replacement therapy. The ultimate goal being translation to the clinic, a particular attention is given to the discrepancies between findings from studies performed in rodents (bothex vivoon primary cells andin vivoon animal models), when compared with clinical data and studies performed on human cells.

scholarly journals Neem Leaf Glycoprotein Partially Rectifies Suppressed Dendritic Cell Functions and Associated T Cell Efficacy in Patients with Stage IIIB Cervical Cancer

2011 ◽  
Vol 18 (4) ◽  
pp. 571-579 ◽  
Author(s):  
Soumyabrata Roy ◽  
Shyamal Goswami ◽  
Anamika Bose ◽  
Krishnendu Chakraborty ◽  
Smarajit Pal ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dendritic Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Stage Iiib ◽  
Immune Functions ◽  
Cell Functions

ABSTRACTMyeloid-derived dendritic cells (DCs) generated from monocytes obtained from stage IIIB cervical cancer (CaCx IIIB) patients show dysfunctional maturation; thus, antitumor T cell functions are dysregulated. In an objective to optimize these dysregulated immune functions, the present study is focused on the ability of neem leaf glycoprotein (NLGP), a nontoxic preparation of the neem leaf, to induce optimum maturation of dendritic cells from CaCx IIIB patients.In vitroNLGP treatment of immature DCs (iDCs) obtained from CaCx IIIB patients results in upregulated expression of various cell surface markers (CD40, CD83, CD80, CD86, and HLA-ABC), which indicates DC maturation. Consequently, NLGP-matured DCs displayed balanced cytokine secretions, with type 1 bias and noteworthy functional properties. These DCs displayed substantial T cell allostimulatory capacity and promoted the generation of cytotoxic T lymphocytes (CTLs). Although NLGP-matured DCs derived from CaCx monocytes are generally subdued compared to those with a healthy monocyte origin, considerable revival of the suppressed DC-based immune functions is notedin vitroat a fairly advanced stage of CaCx, and thus, further exploration ofex vivoandin vivoDC-based vaccines is proposed. Moreover, the DC maturating efficacy of NLGP might be much more effective in the earlier stages of CaCx, where the extent of immune dysregulation is less and, thus, the scope of further investigation may be explored.

Progress in Translational Regulatory T Cell Therapies for Type 1 Diabetes and Islet Transplantation

2020 ◽  
Author(s):  
Braulio A Marfil-Garza ◽  
Joshua Hefler ◽  
Mario Bermudez De Leon ◽  
Rena Pawlick ◽  
Nidheesh Dadheech ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Ex Vivo ◽  
Severe Hypoglycemia ◽  
Cell Therapies ◽  
Current State ◽  
Cellular Transplantation ◽  
And Function

Abstract Regulatory T cells (Tregs) have become highly relevant in the pathophysiology and treatment of autoimmune diseases, such as type 1 diabetes (T1D). As these cells are known to be defective in T1D, recent efforts have explored ex vivo and in vivo Treg expansion and enhancement as a means for restoring self-tolerance in this disease. Given their capacity to also modulate alloimmune responses, studies using Treg-based therapies have recently been undertaken in transplantation. Islet transplantation provides a unique opportunity to study the critical immunological crossroads between auto- and alloimmunity. This procedure has advanced greatly in recent years, and reports of complete abrogation of severe hypoglycemia and long-term insulin independence have become increasingly reported. It is clear that cellular transplantation has the potential to be a true cure in T1D, provided the remaining barriers of cell supply and abrogated need for immune suppression can be overcome. However, the role that Tregs play in islet transplantation remains to be defined. Herein, we synthesize the progress and current state of Treg-based therapies in T1D and islet transplantation. We provide an extensive, but concise, background to understand the physiology and function of these cells and discuss the clinical evidence supporting potency and potential Treg-based therapies in the context of T1D and islet transplantation. Finally, we discuss some areas of opportunity and potential research avenues to guide effective future clinical application. This review provides a basic framework of knowledge for clinicians and researchers involved in the care of patients with T1D and islet transplantation.

scholarly journals Functional Role of pX Open Reading Frame II of Human T-Lymphotropic Virus Type 1 in Maintenance of Viral Loads In Vivo

2000 ◽  
Vol 74 (3) ◽  
pp. 1094-1100 ◽  
Author(s):  
Joshua T. Bartoe ◽  
Björn Albrecht ◽  
Nathaniel D. Collins ◽  
Michael D. Robek ◽  
Lee Ratner ◽  
...  
Keyword(s):  
Virus Type ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Peripheral Blood Mononuclear ◽  
T Lymphotropic Virus ◽  
Viral Loads

ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and is associated with a variety of immune-mediated disorders. The role of four open reading frames (ORFs), located between env and the 3′ long terminal repeat of HTLV-1, in mediating disease is not entirely clear. By differential splicing, ORF II encodes two proteins, p13II and p30II, both of which have not been functionally defined. p13II localizes to mitochondria and may alter the configuration of the tubular network of this cellular organelle. p30II localizes to the nucleolus and shares homology with the transcription factors Oct-1 and -2, Pit-1, and POU-M1. Both p13II and p30II are dispensable for infection and immortalization of primary human and rabbit lymphocytes in vitro. To test the role of ORF II gene products in vivo, we inoculated rabbits with lethally irradiated cell lines expressing the wild-type molecular clone of HTLV-1 (ACH.1) or a clone containing selected mutations in ORF II (ACH.30/13.1). ACH.1-inoculated animals maintained higher HTLV-1-specific antibody titers than animals inoculated with ACH.30/13.1. Viral p19 antigen was transiently detected in ex vivo cultures of peripheral blood mononuclear cells (PBMC) from only two ACH.30/13.1-inoculated rabbits, while PBMC cultures from all ACH.1-inoculated rabbits routinely produced p19 antigen. In only three of six animals exposed to the ACH.p30II/p13IIclone could provirus be consistently PCR amplified from extracted PBMC DNA and quantitative competitive PCR showed the proviral loads in PBMC from ACH.p30II/p13II-infected rabbits to be dramatically lower than the proviral loads in rabbits exposed to ACH. Our data indicate selected mutations in pX ORF II diminish the ability of HTLV-1 to maintain high viral loads in vivo and suggest an important function for p13II and p30II in viral pathogenesis.

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