polidocanol and Disease-Models--Animal

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

To determine the effectiveness of different concentrations of lauromacrogol injections for the treatment of endometriosis in an experimental animal model and to provide an experimental basis for a pre-clinical application of the drug.. After autologous transplantation of endometrial tissue, 40 endometrial cysts were successfully established and randomly divided into three groups: a 1 % lauromacrogol injection group, a 0.5 % lauromacrogol injection group, and cysts without intervention (control group). We measured the changes in the volumes of the cysts in each group. We then compared the volumes of the endometrial implants before and after treatment and between the different groups and examined the histological findings.. A significant difference in the spherical volume was found between the 1 % lauromacrogol injection group (P < 0.05). No significant difference was observed between the volume of the endometrial implants in the 0.5 % lauromacrogol injection group (P > 0.05). Regarding the histopathological observations, in the 1 % lauromacrogol injection group, the epithelia of the cystic implants had atrophied, and the glands had atrophied and were reduced in number. The surrounding stromal tissue had become loose and edematous.. A 1 % lauromacrogol injection produced significant regression of the endometrial foci compared with a 0.5 % lauromacrogol injection or no treatment in a rat model of endometriosis.

Topics: Animals; Cysts; Disease Models, Animal; Endometriosis; Female; Humans; Injections; Polidocanol; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Uterine Diseases

Surgical delay is an invasive method requiring a two-stage surgical procedure. Hence, methods that may serve as an alternative to surgical delay have become the focus of interest of research studies. From a conceptual view, any technique that interrupts the blood flow along the edges of a proposed flap will render the flap ischemic and induce a delay phenomenon. Polidocanol (Aethoxysklerol(®)-Kreussler) was initially used as a local anesthetic. Nowadays, it has been used as a sclerosing agent to treat telangiectasias and varicose veins. The aim of this experimental study was to investigate the effects of polidocanol injected around the periphery of a random flap as a sclerosing agent on flap delay and survival in a random flap model.. A preliminary histopathologic study was performed on two rats to evaluate the sclerosing effect and distribution of polidocanol injection. After the preliminary study, the main study was carried out with three groups: group 1: dorsal flap (n = 10); group 2: dorsal flap + surgical delay (n = 10), group 3: dorsal flap + chemical delay (n = 10).. Tissue samples obtained from the flap and injection area revealed destruction of intradermal vessels. The area affected with sclerosis was limited to 0.1 cm beyond the injection site. Mean viable flap areas were 52.1 ± 4.38% (44.0-58.2) in group 1, 64.8 ± 8.92% (57.2-89.2) in group 2, and 71.8 ± 5.18% (64.0-84.0) in group 3. A statistically highly significant difference was found between the surgical delay and chemical delay groups versus the group without delay (p < 0.001 and p < 0.001, respectively). The difference between the mean viable flap areas was not statistically significant in the surgical and chemical delay groups (p = 0.056).. In conclusion, this study has shown that polidocanol injection around the dorsal flap in the rat is a safe and easy method for nonsurgical delay. The results have shown a flap survival benefit that is superior to controls and equivalent to surgical delay. The clinical application of polidocanol, already in clinical practice for occlusal of telangiectasias, for surgical delay appears feasible.

Topics: Animals; Biopsy, Needle; Disease Models, Animal; Graft Survival; Immunohistochemistry; Injections, Intradermal; Male; Polidocanol; Polyethylene Glycols; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Risk Assessment; Sclerosing Solutions; Surgical Flaps; Treatment Outcome

Foam sclerotherapy has been proven to be a safe and effective treatment for superficial venous insufficiency, but transient visual and neurologic disturbances continue to be reported. These side effects have been theorized to be related to the presence of air or gases in the sclerosing foam that results in "bubble" migration into the cerebral circulation. We present a differing hypothesis that significant amounts of endothelin are released from the treated veins, amounts capable of causing these complications.. We tested the release of endothelin 1 (ET-1) in 12 rats after sclerotherapy with sodium tetradecyl sulfate (STS) in liquid and foam preparations. In 11 human subjects, we measured ET-1 in systemic circulation and in a draining vein after foam sclerotherapy with polidocanol.. Rats treated with STS showed a significant increase in ET-1 levels 1 and 5 minutes after foam sclerotherapy. Patients treated with foam sclerotherapy showed a marked increase in ET-1 levels that correlated significantly with local ET-1 levels.. Evidence of ET-1 release represents a plausible relationship explaining neurologic and visual disturbances reported after sclerotherapy.

Topics: Analysis of Variance; Animals; Disease Models, Animal; Endothelin-1; Gases; Humans; Polidocanol; Polyethylene Glycols; Rats; Sclerosing Solutions; Sclerotherapy; Sodium Tetradecyl Sulfate; Varicose Veins

Sclerotherapy is useful for the treatment of arteriovenous vascular malformations. However, intravascular administration of sclerotic agents into small arteriovenous niduses is often difficult. Extravascular administration of sclerotic agents causes reduction of vascular flow on Doppler echo during clinical sclerotherapy. Therefore, we aimed to investigate whether the extravascular injection of sclerotic agents affects tiny vessels.. Animal study.. The effect of extravascular injection of sclerotic agents on vessels was investigated using rat femoral and superficial inferior epigastric vessels.. After surgical exposure of vessels, absolute ethanol, 5% ethanolamine oleate and 3% polidocanol were injected into perivascular surrounding tissues, and their effect on vessels was evaluated after 14 days using histology and coloured silicone rubber injection.. The integrity of the vascular lumen, endothelial cells and vascular patency were not affected by injection of sclerotic agents.. Attenuation of vascular flow of an arteriovenous shunt after extravascular injection of sclerotic agents is transient and/or trivial and does not cause disruption of vessels. Therefore, sclerotic agents should be delivered to obtain sufficient destruction of arteriovenous malformation lesions and blood flow.

Topics: Animals; Arteriovenous Malformations; Disease Models, Animal; Endothelium, Vascular; Epigastric Arteries; Ethanol; Femoral Artery; Femoral Vein; Follow-Up Studies; Injections; Oleic Acids; Polidocanol; Polyethylene Glycols; Rats; Rats, Wistar; Sclerosing Solutions; Sclerotherapy; Solvents; Tissue Adhesives; Treatment Outcome

Inhibitory effects of HL-n composed of 95 mol% L-α-dimyristoylphosphatidylcholin (DMPC) and 5 mol% polyoxyethylenedodecylether (C(12)(EO)(n), n = 21, 23, or 25) on the growth of human rheumatoid arthritis (RA) fibroblast-like synoviocytes (HFLS-RA) in vitro were examined. Remarkably high inhibitory effects of HL-n on the growth of HFLS-RA cells were obtained. The induction of apoptosis by HL-n was revealed on the basis of TUNEL method. Furthermore, the therapeutic effects of HL-23 using mouse models of arthritis were investigated. Therapeutic effects without joint swelling were obtained in mouse models of RA treated with HL.

Topics: Animals; Apoptosis; Arthritis, Rheumatoid; Dimyristoylphosphatidylcholine; Disease Models, Animal; Humans; Liposomes; Mice; Polidocanol; Polyethylene Glycols; Synovial Membrane

Hybrid liposomes (HLs) composed of vesicular and micellar surfactants have inhibitory effects on the growth of tumor cells in vitro and in vivo. Successful clinical chemotherapy with drug-free HLs to patient with lymphoma has been reported after approval by the Committe of Bioethics. However, the therapeutic effects of HLs on the metastasis of colon carcinoma cells have not yet been elucidated. In this study, the therapeutic effects of HLs composed of L-alpha-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (23) dodecyl ether [C(12)(EO)(23)] on the metastasis of colon carcinoma (Colon26) cells were examined in vivo. Marked high therapeutic effects were obtained in the hepatic metastasis mice model after the treatment with HLs. Furthermore, optical microscopic analysis indicated that HLs could induce the apoptosis of colon carcinoma cells in vivo. No toxicity was observed in the hepatic metastasis mice model after intravenously injecting HLs. Therapeutic effects along with the induction of apoptosis by HLs without any drugs on hepatic metastasis were revealed on the basis of optical microscopic analysis for the first time in vivo.

Topics: Animals; Apoptosis; Carcinoma; Colonic Neoplasms; Dimyristoylphosphatidylcholine; Disease Models, Animal; DNA Fragmentation; DNA, Neoplasm; Dose-Response Relationship, Drug; Liposomes; Liver Neoplasms; Mice; Mice, Inbred BALB C; Polidocanol; Polyethylene Glycols

Sclerosing therapy has in recent studies showed promising results in patients with clinically and ultrasonographically diagnosed tendinosis in Achilles and patellar tendons. The aim of this investigation was to study the presence of intratendinous colour Doppler (CD) flow in horses with clinically diagnosed chronic tendinopathy and to test if experience from human studies could be extrapolated to horses. Special interest was focused on the treatment with sclerosing therapy and whether we could obtain the same successful peroperative findings as in humans. Four horses with clinically diagnosed unilateral chronic tendinosis in the forelimbs were examinated with both grey-scale ultrasonography (US) and CD. The horses were to be euthanised according to standard procedure is such cases. The US findings were used for guidance of sclerosing therapy. All horses showed abnormal findings on US, especially intratendinous neovascularisation in the affected limb but not in the contralateral limb. The CD findings had the same appearance as seen in human Achilles tendons with chronic tendinopathy. In all cases the intratendinous neovascularisation was successfully "shut down" peroperatively. The horses showed no signs of discomfort or worsening of symptoms during the short follow-up period after the procedure. The results indicate that the promising results from human medicine might be transferred to treatment of horses with chronic tendinopathy. In the future it will hopefully be possible to use the model from overused tendons in the horse to determine the best treatment of overuse injuries in humans as well. The animal model will allow experimental studies including substantial tissue sampling for mechanical and molecular biological analysis.

Topics: Animals; Disease Models, Animal; Horse Diseases; Horses; Humans; Polidocanol; Polyethylene Glycols; Sclerosing Solutions; Tendinopathy; Tendons; Ultrasonography, Doppler, Color

The treatment of hemangiomas and vascular malformations in the soft tissue presents several difficult problems. Transarterial embolization and/or percutaneous sclerosing therapy are useful for such lesions, but the effectiveness of these therapies is often partial, and serious problems like ulceration and tissue necrosis may occur. Therefore, we examined the efficacy of intraarterial injection of polidocanol solution as an embolic agent for hemangiomas and vascular malformations using the rabbit kidney. Three embolic agents were compared with polidocanol solution (polidocanol 3%, n = 5; absolute ethanol, n = 5; n-butyl-2 cyanoacrylate: NBCA, n = 5; polyvinyl alcohol: PVA, n = 5). All embolizations were followed by angiography and resection after a week. Results showed that absolute ethanol (n = 5), NBCA (n = 4) and PVA (n = 1) embolized completely. In the specimens, this led to cell necrosis throughout the kidney. In contrast, polidocanol (n = 5) obstructed neither the main trunk of the renal artery nor the peripheral capillary arteries following angiography. In the specimens, the inner medulla of the kidney suffered necrosis. However, residual tissue with massive fibrotic change was seen. These results suggest the efficacy of "embolosclerosing" treatment for capillary vascular lesions and the possibility of alleviating complications from such therapy.

Topics: Animals; Disease Models, Animal; Embolization, Therapeutic; Hemangioma; Injections, Intra-Arterial; Kidney Neoplasms; Polidocanol; Polyethylene Glycols; Rabbits; Renal Artery; Sclerosing Solutions

In order to create an experimental model for the carpal tunnel syndrome without the use of the commonly applied foreign bodies (silicone or rubber tubes, tourniquets etc.), the present study tried to induce a chemically provoked compression of the median nerve in rabbits. In 9 female rabbits 1 ml of Aethoxskerol 3% (Hydrox-polyethoxy dodecan) was instilled into the carpal tunnel around the median nerve after visualisation of the nerve. The other foreleg served as the control and was treated with the same amount of saline solution. Electroneurophysiologic parameters were registered preoperatively, 1 month and 6 months post surgery and histomorphologic investigations by light and electron microscopy were performed after 6 months. 6 months after treatment with Aethoxysklerol, a statistically significant lengthening of the distal latency period as well as a significant reduction of the compound potential amplitude could be observed. In accordance with these findings, morphological investigation revealed the presence of extensive granulation tissue around the median nerve together with signs of demyelination. Our results indicate that we were able to produce the development of extensive granulation tissue in the carpal tunnel of rabbits with subsequent compression of the median nerve which was confirmed by histomorphologic investigation as well as by measurement of nerve conductive velocity.

Topics: Animals; Carpal Tunnel Syndrome; Disease Models, Animal; Median Nerve; Microscopy, Electron; Polidocanol; Polyethylene Glycols; Rabbits; Reaction Time; Sclerosing Solutions; Synaptic Transmission

Differential effects of adriamycin cytotoxicity and its cellular uptake were assessed in murine tumor models utilising adriamycin alone and in combination with nontoxic concentrations of nonionic polyoxyethylated lauryl ether surfactants Brij 30 and Brij 35. Parental P388 murine leukemia cell line sensitive to adriamycin, subline of P388 murine leukemia resistant to adriamycin, sarcoma-180 and Ehrlich ascites tumor were employed in this study. The results indicate an enhanced DNA biosynthesis inhibition by adriamycin when used in combination with Brij 30 or Brij 35 in all the murine tumor models. The increase in adriamycin cytotoxicity was due to an increased accumulation of adriamycin observed in the tumor models used. The present investigation demonstrates the necessity of utilising surface-active drug-response modulators to enhance the cytotoxicity of anticancer drugs and circumvent drug resistance.

Topics: Animals; Cell Membrane Permeability; Disease Models, Animal; DNA Replication; Doxorubicin; Drug Interactions; Mice; Polidocanol; Polyethylene Glycols; Surface-Active Agents; Thymidine; Tritium; Tumor Cells, Cultured