In vivo studies with a Candida tropicalis isolate exhibiting paradoxical growth in vitro in the presence of high concentration of caspofungin

Background: Diclofenac sodium (DS) injection is widely used in the management of acute or chronic pain and inflammatory diseases. It incorporates 20 % w/v Transcutol-P as a solubilizer to make the stable injectable formulation. However, the use of Transcutol-P in high concentration leads to adverse effects such as severe nephrotoxicity, etc. Some advancements resulted in the formulation of an aqueous based injectable but that too used benzyl alcohol reported to be toxic for human use. Objective: To develop an injectable self-micro emulsifying drug delivery system (SMEDDS) as a novel carrier of DS for prompt release with better safety and efficacy. Methods: A solubility study was performed with different surfactants and co-surfactants. The conventional stirring method was employed for the formulation of SMEDDS. Detailed in vitro characterization was done for different quality control parameters. In vivo studies were performed using Wistar rats for pharmacokinetic evaluation, toxicological analysis, and analgesic activity. Results: The optimized formulation exhibited good physical stability, ideal globule size (156±0.4 nm), quick release, better therapeutics, and safety, increase in LD50 (221.9 mg/kg) to that of the commercial counterpart (109.9 mg/kg). Further, pre-treatment with optimized formulation reduced the carrageenan-induced rat paw oedema by 88±1.2 % after 4 h, compared to 77±1.6 % inhibition with commercial DS formulation. Moreover, optimized formulation significantly (p<0.05) inhibited the pain sensation in the acetic-acid induced writhing test in mice compared to its commercial equivalent with a better pharmacokinetic profile. Conclusion: The above findings confirmed that liquid SMEDDS could be a successful carrier for the safe and effective delivery of DS

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(E)-2-Hexenal Can Stimulate Botrytis cinerea Growth in vitro and on Strawberries in vivo during Storage

Journal of the American Society for Horticultural Science ◽

10.21273/jashs.123.5.875 ◽

1998 ◽

Vol 123 (5) ◽

pp. 875-881 ◽

Cited By ~ 47

Author(s):

Elazar Fallik ◽

Douglas D. Archbold ◽

Thomas R. Hamilton-Kemp ◽

Ann M. Clements ◽

Randy W. Collins ◽

...

Keyword(s):

Botrytis Cinerea ◽

Spore Germination ◽

Mode Of Action ◽

Mycelial Growth ◽

Titratable Acidity ◽

Soluble Solids ◽

In Vivo Studies ◽

High Concentration

Some plant-derived natural volatile compounds exhibit antifungal properties and may offer an opportunity to control the causes of postharvest spoilage without affecting quality of, or leaving a residue on, fresh produce. The natural wound volatile (E)-2-hexenal has exhibited significant antifungal activity in earlier studies, but effects on spore germination and mycelial growth have not been separated, nor has the inhibitory mode of action been determined. To determine the efficacy of (E)-2-hexenal for control of Botrytis cinerea Pers. ex Fr. spore germination and mycelial growth, and to examine the mode of action, in vitro and in vivo studies were performed. Under in vitro bioassay conditions, spore germination was more sensitive to the compound than was mycelial growth. Vapor from 10.3 μmol of (E)-2-hexenal in a 120-mL petri dish completely inhibited spore germination. However, 85.6 μmol of (E)-2-hexenal was required to completely inhibit mycelial growth. Lower concentrations of the compound (5.4 and 10.3 μmol) significantly stimulated mycelial growth, especially when the volatile was added 2 days following inoculation. Mycelial growth did not occur as long as the vapor-phase concentration was 0.48 μmol·L-1 or greater. Light microscopy analysis indicated that a high concentration of volatile compound dehydrated fungal hyphae and disrupted their cell walls and membranes. Exposure of B. cinerea-inoculated and non-inoculated strawberry (Fragaria ×ananassa Duch.) fruit in 1.1-L low-density polyethylene film-wrapped containers to vapor of (E)-2-hexenal at 85.6 or 856 μmol (10 or 100 mL, respectively) per container for durations of 1, 4, or 7 days during 7 days of storage at 2 °C promoted the incidence of B. cinerea during subsequent shelf storage at 20 to 22 °C. Loss of fruit fresh mass and fruit firmness during storage at 22 °C was increased by (E)-2-hexenal treatment, but fruit total soluble solids, pH, titratable acidity, and color (L, C, and H values) were not affected. Thus, maintenance of a high vapor-phasel level of (E)-hexenal, perhaps >0.48 μmol·L-1, may be necessary to inhibit mycelial growth and avoid enhancing postharvest mold problems, while significantly higher levels may be necessary to completely eliminate the pathogen.

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Efficacy of a Semi Automated Commercial Closed System for Autologous Leukocyte- and Platelet-Rich Plasma (l-prp) Production in Dogs: A Preliminary Study

Animals ◽

10.3390/ani10081342 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1342 ◽

Cited By ~ 1

Author(s):

Roberta Perego ◽

Eva Spada ◽

Luciana Baggiani ◽

Piera Anna Martino ◽

Daniela Proverbio

Keyword(s):

Platelet Count ◽

Closed System ◽

Whole Blood ◽

Platelet Rich Plasma ◽

In Vivo Studies ◽

High Concentration ◽

Commercial System ◽

Thrombin Activation

Background: To characterize the cellular composition (platelets, erythrocytes, and leukocytes) and determine platelet-derived growth factor isoform BB (PDGF-BB) concentration in canine leukocyte- and platelet rich plasma (L-PRP) produced using a commercial semi-automated closed system. Methods: Twenty milliliters of citrated whole blood were obtained from 30 healthy un-sedated canine blood donors and processed using a semi-automated completely closed commercial system (CPUNT 20, Eltek group, Casale Monferrato, Alessandria, Italy) according to the manufacturer’s instructions. Erythrocyte, leukocyte, and platelet counts were determined in both whole blood (WB) and resultant L-PRP. The PDGF-BB concentration was evaluated after bovine thrombin activation of 10 L-PRP samples. Results: This commercial system produced on average 2.3 ± 0.7 mL of L-PRP containing a high concentration of platelets (767,633 ± 291,001 μL, p < 0.001), with a 4.4 fold increase in platelet count, lower concentration of erythrocytes (528,600 ± 222,773 μL, p < 0.001) and similar concentration of leukocytes (8422 ± 6346 μL, p = 0.9918) compared with WB. L-PRP had an average of 3442 ± 2061 pg/mL of PDGF-BB after thrombin activation. Neutrophils, lymphocytes and monocytes average percent content in L-PRP was 14.8 ± 13.2, 71.7 ± 18.5 and 10.7 ± 6.4, respectively. Conclusion: Sterile canine L-PRP prepared using this semi-automated closed system is easy to obtain, produces a significant increase in platelet count compared to WB and contains a detectable concentration of PDGF-BB after activation. Additional in vitro and in vivo studies are needed to assess inflammatory markers concentration and the therapeutic efficacy of this L-PRP in dogs.

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Q-VE-OPh, a Negative Control for O-Phenoxy-Conjugated Caspase Inhibitors

Journal of Cell Death ◽

10.4137/jcd.s4455 ◽

2010 ◽

Vol 3 ◽

pp. JCD.S4455 ◽

Cited By ~ 2

Author(s):

Benjamin Southerland ◽

Kashmira Kulkarni-Datar ◽

Chanel Keoni ◽

Rebecca Bricker ◽

William C. Grunwald ◽

...

Keyword(s):

Dna Fragmentation ◽

Ion Trap ◽

Inhibitory Effect ◽

Negative Control ◽

In Vivo Studies ◽

High Concentration ◽

Caspase Inhibitors ◽

Initiator Caspases

The broad-spectrum apoptosis (caspase) inhibitor, Q-VD-OPh, has been shown to have no side effects and is effective at a much lower concentration than other FMK-type caspase inhibitors. However, an appropriate negative control to use with this inhibitor has not been available. In this study, we developed and analyzed a new compound, based on the Q-VD-OPh backbone, which acts as a cognate negative control. To create the negative control, we substituted a glutamate residue for the aspartate residue to create Q-VE-OPh, thereby retaining the identical charge and molecular properties with only the addition of an extra -CH2 group. The purity and quality were assessed by ion trap mass spectrometry and verified by nuclear magnetic resonance. We determined the effectiveness of Q-VE-OPh, in comparison to Q-VD-OPh, to prevent DNA fragmentation in human Jurkat T leukemia cells that were induced to undergo apoptosis. DNA fragmentation was analyzed by agarose gel electrophoresis for the presence of DNA laddering, the hallmark indicator of apoptosis. Our results indicate that apoptosis was potently inhibited by Q-VD-OPh. In stark contrast, Q-VE-OPh did not inhibit apoptosis at a similar dose but required at least 20 times greater concentration than Q-VD-OPh to have any inhibitory effect. Western blot analysis showed that Q-VE-OPh was similarly less effective at inhibiting the activation of the extrinsic (caspase 8) and intrinsic (caspase 9) initiator caspases. Cell proliferation and viability studies further demonstrate that Q-VE-OPh is non-toxic, even at high concentration. Our data indicate that the specificity, effectiveness, and absence of toxicity of Q-VE-OPh provides the appropriate and superior negative control for in vitro and in vivo studies when analyzing the effects of o-phenoxy caspase inhibitors.

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Regulation of vascular endothelial growth factor expression in human endometrium by steroids and hypoxia: In vitro and in vivo studies

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(97)86195-3 ◽

1998 ◽

Vol 5 (1) ◽

pp. 69A-69A

Author(s):

A SHARKEY ◽

D CHARNOCKJONES ◽

K DAY ◽

H SOWTER ◽

L SVENSSON ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Human Endometrium ◽

In Vivo Studies ◽

Vascular Endothelial ◽

Factor Expression ◽

Growth Factor Expression ◽

Endothelial Growth Factor

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In vitro and in vivo studies of new cationic Zn(II)‐benzonaphthoporphyrazines as photosensitizers for PDT

Journal of Porphyrins and Phthalocyanines ◽

10.1002/jpp.373.abs ◽

2001 ◽

Vol 5 (8) ◽

pp. 645-651

Author(s):

M. Peeva ◽

M. Shopova ◽

U. Michelsen ◽

D. Wöhrle ◽

G. Petrov ◽

...

Keyword(s):

In Vivo Studies

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Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0198 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S198-S198

Author(s):

Joseph R Meno ◽

Thien-son K Nguyen ◽

Elise M Jensen ◽

G Alexander West ◽

Leonid Groysman ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Brain Activation ◽

In Vivo Studies ◽

Blood Flow Response ◽

Flow Response

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Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648988 ◽

1994 ◽

Vol 72 (06) ◽

pp. 942-946 ◽

Cited By ~ 20

Author(s):

Raffaele Landolfi ◽

Erica De Candia ◽

Bianca Rocca ◽

Giovanni Ciabattoni ◽

Armando Antinori ◽

...

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Primary Source ◽

In Vivo Studies ◽

Low Molecular Weight ◽

Heparin Administration ◽

To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

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