Analysis of minocycline as a countermeasure against acute radiation syndrome.

PubMed

Mehrotra, Shalini; Pecaut, Michael J; Gridley, Daila S

2012-01-01

To evaluate the impact of an antibiotic, minocycline, on several immune parameters in response to radiation in a mouse model. C57BL/6 mice were treated with minocycline (i.p.) for 5 days, beginning immediately before radiation with 1-3 Gy (60)Co γ-rays. Spleen and blood were collected on day 4 post-irradiation. Cell populations were determined in the blood and spleen. Splenocytes were activated with anti-CD3 antibody for 48 h and cytokines were quantified. Minocycline increased the counts and/or percentages of splenic macrophages, granulocytes, natural killer, T- and CD8(+) T-cells (p<0.05 versus radiation alone). Minocycline significantly increased the expression of interleukin-1α and β, which are radioprotective, as well as the ones of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor, which accelerate neutrophil recovery (p<0.05 versus radiation alone), while suppressing cytokines that could prevent hematopoiesis, e.g. macrophage inflammatory protein-1α, tumor necrosis factor-α and interferon-γ. These data indicate that minocycline should be further tested for use in restoration of the hematopoietic system after radiation exposure.

Efficacy of extended-release 45 mg oral minocycline and extended-release 45 mg oral minocycline plus 15% azelaic acid in the treatment of acne rosacea.

PubMed

Jackson, J Mark; Kircik, Leon H; Lorenz, Douglas J

2013-03-01

Rosacea is one of the most commonly occurring dermatoses treated by dermatologists. There are multiple therapeutic options available for the treatment of papulopustular rosacea. Rosacea is an inflammatory condition, classically presenting with flushing and/or blushing along with erythema, edema, telangiectasia, papules, pustules, and nodules of the face. Minocycline, a member of the tetracycline family, has demonstrated benefit in the treatment of inflammatory lesions in patients with rosacea. This manuscript highlights the use of a new sustained-release low-dose minocycline 45 mg tablet, with or without azelaic acid, for the treatment of papulopustular rosacea.

Efficacy of prophylactic minocycline treatment for skin toxicities induced by erlotinib plus gemcitabine in patients with advanced pancreatic cancer: a retrospective study.

PubMed

Shinohara, Akira; Ikeda, Masafumi; Okuyama, Hiroyuki; Kobayashi, Misaki; Funazaki, Hideki; Mitsunaga, Shuichi; Shimizu, Satoshi; Ohno, Izumi; Takahashi, Hideaki; Ichida, Yasuhiko; Takahashi, Kunio; Okusaka, Takuji; Saitoh, Shinichiro

2015-06-01

Erlotinib has been reported as being associated with a high incidence of skin toxicities such as acneiform rash, paronychia, and xerosis. The aim of this study was to evaluate the efficacy of prophylactic minocycline treatment for the skin toxicities induced by erlotinib as compared with deferred minocycline treatment in patients with pancreatic cancer treated with erlotinib plus gemcitabine. A total of 96 patients were studied retrospectively, of whom 44 received prophylactic minocycline between August 2012 and June 2013 and 52 received deferred minocycline treatment between August 2011 and July 2012 at the National Cancer Center Hospital East, Kashiwa, Japan. In the prophylactic minocycline group, 200 mg/day oral minocycline was prophylactically administered during the treatment period. The incidence rate of acneiform rash and xerosis of any grade during the first 6 weeks of treatment was significantly reduced in the prophylactic minocycline group compared with the deferred minocycline treatment group (47.7 vs. 80.8%, p<0.001; 2.3 vs. 19.2%, p=0.01). Multivariate analysis identified prophylactic minocycline as a significant independent factor associated with the incidence of acneiform rash and xerosis of any severity (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.06-0.46, p<0.001; OR 0.11, 95% CI 0.01-0.90, p=0.04). Prophylactic minocycline appears to be useful for the management of erlotinib-related acneiform rash and xerosis during chemotherapy in patients with advanced pancreatic cancer.

Minocycline prevents cholinergic loss in a mouse model of Down's syndrome.

PubMed

Hunter, Christopher L; Bachman, David; Granholm, Ann-Charlotte

2004-11-01

Individuals with Down's syndrome develop Alzheimer's-like pathologies comparatively early in life, including progressive degeneration of basal forebrain cholinergic neurons (BFCNs). Cholinergic hypofunction contributes to dementia-related cognitive decline and remains a target of therapeutic intervention for Alzheimer's disease. In light of this, partial trisomy 16 (Ts65Dn) mice have been developed to provide an animal model of Down's syndrome that exhibits progressive loss of BFCNs and cognitive ability. Another feature common to both Down's syndrome and Alzheimer's disease is neuroinflammation, which may exacerbate neurodegeneration, including cholinergic loss. Minocycline is a semisynthetic tetracycline with antiinflammatory properties that has demonstrated neuroprotective properties in certain disease models. Consistent with a role for inflammatory processes in BFCN degeneration, we have shown previously that minocycline protects BFCNs and improves memory in mice with acute, immunotoxic BFCN lesions. We now report that minocycline treatment inhibits microglial activation, prevents progressive BFCN decline, and markedly improves performance of Ts65Dn mice on a working and reference memory task. Minocycline is an established antiinflammatory and neuroprotective drug and may provide a novel approach to treat specific AD-like pathologies.

[Minocycline pneumonitis and eosinophilia].

PubMed

Fink, N; Mouallem, M

2000-06-15

Pneumonitis with eosinophilia is one of the less common and severe adverse effects of minocycline. The disease evolves in days or weeks from the beginning of treatment, and is usually characterized by dyspnea, fever and bilateral infiltrates in the chest X-ray. With cessation of the antibiotic, and sometimes adding cortico-steroids, clinical and roentgenological resolution follow. We present a case given minocycline for folliculitis and 3 weeks later fever, cough and shortness of breath developed. The clinical and roentgenological course was consistent with minocycline pneumonitis accompanied by eosinophilia.

Comparison of minocycline and azithromycin for the treatment of mild scrub typhus in northern China.

PubMed

Zhao, Minxing; Wang, Ting; Yuan, Xiaoyu; Du, Weiming; Lin, Miaoxin; Shen, Yanbo

2016-09-01

Scrub typhus, caused by Orientia tsutsugamushi, has recently emerged in northern China where the disease had not been known to exist. Although doxycycline and azithromycin are the recommended agents for the treatment of scrub typhus, clinical responses depend both on the susceptibilities of various O. tsutsugamushi strains and the severity of the disease. A retrospective analysis was conducted on patients diagnosed with mild scrub typhus from August 2013 to January 2016 in the Affiliated Hospital of Nantong University, northern China. A total of 40 patients who received minocycline treatment and 34 patients who received azithromycin treatment were included in the analysis. All patients except one defervesced within 120 h after initiating antimicrobial therapy. Kaplan-Meier curves in association with log-rank test showed that the median time to defervescence was significantly shorter for the minocycline-treated group than the azithromycin-treated group (P = 0.003). There were no serious adverse events during treatment. No relapse occurred in either group during the 1-month follow-up period. In conclusion, both minocycline and azithromycin are effective and safe for the treatment of mild scrub typhus, but minocycline is more active than azithromycin against O. tsutsugamushi infection acquired in northern China. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Minocycline and Tigecycline: What Is Their Role in the Treatment of Carbapenem-Resistant Gram-Negative Organisms?

PubMed

Shankar, Chaitra; Nabarro, Laura E B; Anandan, Shalini; Veeraraghavan, Balaji

2017-06-01

Carbapenem-resistant organisms are increasingly common worldwide, particularly in India and are associated with high mortality rates especially in patients with severe infection such as bacteremia. Existing drugs such as carbapenems and polymyxins have a number of disadvantages, but remain the mainstay of treatment. The tetracycline class of antibiotics was first produced in the 1940s. Minocycline, tetracycline derivative, although licensed for treatment of wide range of infections, has not been considered for treatment of multidrug-resistant organisms until recently and needs further in vivo studies. Tigecycline, a derivative of minocycline, although with certain disadvantages, has been frequently used in the treatment of carbapenem-resistant organisms. In this article, we review the properties of minocycline and tigecycline, the common mechanisms of resistance, and assess their role in the management of carbapenem-resistant organisms.

Adjunctive minocycline treatment for major depressive disorder: A proof of concept trial.

PubMed

Dean, Olivia M; Kanchanatawan, Buranee; Ashton, Melanie; Mohebbi, Mohammadreza; Ng, Chee Hong; Maes, Michael; Berk, Lesley; Sughondhabirom, Atapol; Tangwongchai, Sookjaroen; Singh, Ajeet B; McKenzie, Helen; Smith, Deidre J; Malhi, Gin S; Dowling, Nathan; Berk, Michael

2017-08-01

Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder. A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery-Asberg Depression Rating Scale (primary outcome), Clinical Global Impression-Improvement and Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au , #ACTRN12612000283875. Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery-Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression-Improvement score - effect size (95% confidence interval) = -0.62 [-1.8, -0.3], p = 0.02; Quality of Life Enjoyment and Satisfaction Questionnaire score - effect size (confidence interval) = -0.12 [0.0, 0.2], p < 0.001; and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score - 0.79 [-4

Efficacy of photodynamic therapy combined with minocycline for treatment of moderate to severe facial acne vulgaris and influence on quality of life.

PubMed

Xu, Xinghua; Zheng, Yi; Zhao, Zigang; Zhang, Xin; Liu, Pengxiang; Li, Chengxin

2017-12-01

Acne vulgaris is a prevalent skin disorder impairing both physical and psychosocial health. This study was designed to investigate the effectiveness of photodynamic therapy (PDT) combined with minocycline in moderate to severe facial acne and influence on quality of life (QOL). Ninety-five patients with moderate to severe facial acne (Investigator Global Assessment [IGA] score 3-4) were randomly treated with PDT and minocycline (n = 48) or minocycline alone (n = 47). All patients took minocycline hydrochloride 100 mg/d for 4 weeks, whereas patients in the minocycline plus PDT group also received 4 times PDT treatment 1 week apart. IGA score, lesion counts, Dermatology Life Quality Index (DLQI), and safety evaluation were performed before treatment and at 2, 4, 6, and 8 weeks after enrolment. There were no statistically significant differences in characteristics between 2 treatment groups at baseline. Minocycline plus PDT treatment led to a greater mean percentage reduction from baseline in lesion counts versus minocycline alone at 8 weeks for both inflammatory (-74.4% vs -53.3%; P < .001) and noninflammatory lesions (-61.7% vs -42.4%; P < .001). More patients treated with minocycline plus PDT achieved IGA score <2 at study end (week 8: 30/48 vs 20/47; P < .05). Patients treated with minocycline plus PDT got significant lower DLQI at 8 weeks (4.4 vs 6.3; P < .001). Adverse events were mild and manageable. Compared with minocycline alone, the combination of PDT with minocycline significantly improved clinical efficacy and QOL in moderate to severe facial acne patients. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Drug repurposing of minocycline against dengue virus infection.

PubMed

Leela, Shilpa Lekshmi; Srisawat, Chatchawan; Sreekanth, Gopinathan Pillai; Noisakran, Sansanee; Yenchitsomanus, Pa-Thai; Limjindaporn, Thawornchai

2016-09-09

Dengue virus infection is one of the most common arthropod-borne viral diseases. A complex interplay between host and viral factors contributes to the severity of infection. The antiviral effects of three antibiotics, lomefloxacin, netilmicin, and minocycline, were examined in this study, and minocycline was found to be a promising drug. This antiviral effect was confirmed in all four serotypes of the virus. The effects of minocycline at various stages of the viral life cycle, such as during viral RNA synthesis, intracellular envelope protein expression, and the production of infectious virions, were examined and found to be significantly reduced by minocycline treatment. Minocycline also modulated host factors, including the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). The transcription of antiviral genes, including 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 3 (OAS3), and interferon α (IFNA), was upregulated by minocycline treatment. Therefore, the antiviral activity of minocycline may have a potential clinical use against Dengue virus infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Could lengthening minocycline therapy better treat early syphilis?

PubMed

Shao, Li-Li; Guo, Rui; Shi, Wei-Jie; Liu, Yuan-Jun; Feng, Bin; Han, Long; Liu, Quan-Zhong

2016-12-01

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Minocycline, a representative tetracycline derivative, has the greatest antimicrobial activity among all tetracyclines. There are few reports about treating syphilis with minocycline because there is a lack of efficacy data from controlled trials. We compared the rates of serological cure in patients with early syphilis who were treated with minocycline or benzathine penicillin G (BPG).During the study period, a total of 40 syphilis patients received the BPG treatment, which was a single intramuscular dose of 2.4 million units of BPG, and 156 patients were treated with minocycline; 77 patients were placed in the 2-week, standard minocycline therapy group and received 100 mg of minocycline orally, twice daily for 14 days, and 79 patients were placed in the 4-week, lengthened minocycline therapy group and received 100 mg of minocycline orally, twice daily for 28 days. The outcome of interest was the rate of serological cure in these patients.At the end of the 2-year follow-up, the serological cure rate of the 4-week, lengthened minocycline therapy group (87.34%) was higher than that of both the 2-week, standard minocycline therapy group (72.73%) and the BPG treatment group (77.50%). In addition, the curative effect of the 4-week, lengthened minocycline therapy was significantly greater than that of the 2-week, standard minocycline therapy in patients who were aged >40 years; exhibited an initial rapid plasma reagin titer ≥1: 32; or exhibited secondary syphilis (P = 0.000, 0.008, 0.000; <0.05).Minocycline appears to be an effective agent for treating early syphilis, especially when applied as a 4-week, lengthened therapy.

Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration

PubMed Central

Ali, Sumia; Driscoll, Heather E.; Newton, Victoria L.; Gardiner, Natalie J.

2014-01-01

Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using

A pilot study of minocycline for the prevention of paclitaxel-associated neuropathy: ACCRU study RU221408I.

PubMed

Pachman, Deirdre R; Dockter, Travis; Zekan, Patricia J; Fruth, Briant; Ruddy, Kathryn J; Ta, Lauren E; Lafky, Jacqueline M; Dentchev, Todor; Le-Lindqwister, Nguyet Anh; Sikov, William M; Staff, Nathan; Beutler, Andreas S; Loprinzi, Charles L

2017-11-01

Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Given that extensive animal data suggest that minocycline may prevent chemotherapy-induced neurotoxicity, the purpose of this pilot study was to investigate the efficacy of minocycline for the prevention of CIPN and the P-APS. Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks and were randomized to receive minocycline 200 mg on day 1 followed by 100 mg twice daily or a matching placebo. Patients completed (1) an acute pain syndrome questionnaire daily during chemotherapy to measure P-APS and (2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment, to measure CIPN. Forty-seven patients were randomized. There were no remarkable differences noted between the minocycline and placebo groups for the overall sensory neuropathy score of the EORTC QLQ-CIPN20 or its individual components, which evaluate tingling, numbness and shooting/burning pain in hands and feet. However, patients taking minocycline had a significant reduction in the daily average pain score attributed to P-APS (p = 0.02). Not only were no increased toxicities reported with minocycline, but there was a significant reduction in fatigue (p = 0.02). Results of this pilot study do not support the use of minocycline to prevent CIPN, but suggest that it may reduce P-APS and decrease fatigue; further study of the impact of this agent on those endpoints may be warranted.

Side Effects of Minocycline Treatment in Patients with Fragile X Syndrome and Exploration of Outcome Measures

ERIC Educational Resources Information Center

Utari, Agustini; Chonchaiya, Weerasak; Rivera, Susan M.; Schneider, Andrea; Hagerman, Randi J.; Faradz, Sultana M. H.; Ethell, Iryna M.; Nguyen, Danh V.

2010-01-01

Minocycline can rescue the dendritic spine and synaptic structural abnormalities in the fragile X knock-out mouse. This is a review and preliminary survey to document side effects and potential outcome measures for minocycline use in the treatment of individuals with fragile X syndrome. We surveyed 50 patients with fragile X syndrome who received…

Microbial changes in patients with acute periodontal abscess after treatment detected by PadoTest.

PubMed

Eguchi, T; Koshy, G; Umeda, M; Iwanami, T; Suga, J; Nomura, Y; Kawanami, M; Ishikawa, I

2008-03-01

To investigate changes in bacterial counts in subgingival plaque from patients with acute periodontal abscess by IAI-PadoTest. Ninety-one patients were randomly allocated to either test or control groups. In all the patients, pockets with acute periodontal abscess were irrigated with sterilized physiological saline, and in the test group, 2% minocycline hydrochloride ointment was applied once into the pocket in addition. Subgingival plaque samples were collected by paper point before treatment and 7 days after treatment. The total bacterial count was determined and Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, were detected using IAI-PadoTest, a DNA/RNA probe method. The total bacterial count decreased in both groups, with a significant decrease in the test group. The counts and number of sites positive for P. gingivalis, T. forsythia and T. denticola significantly decreased in the test group after treatment, compared with those in the control group. Pocket depth decreased in the both groups, with a statistically significant decrease in the test group. Topical treatment with minocycline in pockets with acute periodontal abscess was effective in reducing the bacterial counts as shown by the microbiological investigation using PadoTest 4.5.

Minocycline Protection of Neomycin Induced Hearing Loss in Gerbils

PubMed Central

Robinson, Alan M.; Vujanovic, Irena; Richter, Claus-Peter

2015-01-01

This animal study was designed to determine if minocycline ameliorates cochlear damage is caused by intratympanic injection of the ototoxic aminoglycoside antibiotic neomycin. Baseline auditory-evoked brainstem responses were measured in gerbils that received 40 mM intratympanic neomycin either with 0, 1.2, or 1.5 mg/kg intraperitoneal minocycline. Four weeks later auditory-evoked brainstem responses were measured and compared to the baseline measurements. Minocycline treatments of 1.2 mg/kg and 1.5 mg/kg resulted in significantly lower threshold increases compared to 0 mg/kg, indicating protection of hearing loss between 6 kHz and 19 kHz. Cochleae were processed for histology and sectioned to allow quantification of the spiral ganglion neurons and histological evaluation of organ of Corti. Significant reduction of spiral ganglion neuron density was demonstrated in animals that did not receive minocycline, indicating that those receiving minocycline demonstrated enhanced survival of spiral ganglion neurons, enhanced survival of sensory hairs cells and spiral ganglion neurons, and reduced hearing threshold elevation correlates with minocycline treatment demonstrating that neomycin induced hearing loss can be reduced by the simultaneous application of minocycline. PMID:25950003

Intravenous Minocycline: A Review in Acinetobacter Infections.

PubMed

Greig, Sarah L; Scott, Lesley J

2016-10-01

Intravenous minocycline (Minocin ® ) is approved in the USA for use in patients with infections due to susceptible strains of Gram-positive and Gram-negative pathogens, including infections due to Acinetobacter spp. Minocycline is a synthetic tetracycline derivative that was originally introduced in the 1960s. A new intravenous formulation of minocycline was recently approved and introduced to address the increasing prevalence of multidrug-resistant (MDR) pathogens. Minocycline shows antibacterial activity against A. baumannii clinical isolates worldwide, and exhibits synergistic bactericidal activity against MDR and extensively drug-resistant (XDR) A. baumannii isolates when combined with other antibacterial agents. In retrospective studies, intravenous minocycline provided high rates of clinical success or improvement and was generally well tolerated among patients with MDR or carbapenem-resistant A. baumannii infections. While randomized clinical trial data would be useful to fully establish the place of minocycline in the management of these infections for which there are currently very few available options, clinical trials in patients with infections due to Acinetobacter spp. are difficult to perform. Nevertheless, current data indicate a potential role for intravenous minocycline in the treatment of patients MDR A. baumannii infections, particularly when combined with a second antibacterial agent (e.g. colistin).

Photo-onycholysis from minocycline. Side effects of minocycline therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kestel, J.L. Jr.

1981-07-01

Minocycline, prescribed for a patient with acne, produced a photosensitivity reaction (photo-onycholysis) involving the fingernails. The onset of this reaction coincided with an increase in sun exposure and cleared several months later, when the drug was discontinued. This type of reaction has been reported to occur in patients taking tetracycline or a member of the tetracycline group of antibiotics, of which minocycline is a member. This appears to be first report of photo-onycholysis due to minocycline.

Analysis of Minocycline as a Radioprotectant

NASA Astrophysics Data System (ADS)

Mehrotra, Shalini

Exposure to radiation is increasing in a variety of settings including space exploration, diagnostic medical procedures and radiotherapy. Cells of the hematopoietic system, such as white blood cells (WBC), are especially sensitive to radiation and their decline can result in Acute Radiation Syndrome (ARS). Radiotherapy is often used for cancers of the central nervous system (CNS), but includes the risk for normal tissue damage, often leading to cognitive impairment. The literature suggests that tetracyclines can be radioprotectors of the hematopoietic system with potential utility in radiation emergencies and anticancer radiotherapy. Minocycline, a semisynthetic tetracycline derivative, has anti-inflammatory, free radical scavenging, anti-apoptotic and anti-angiogenic properties with exceptional penetration into the CNS. These qualities make it a viable candidate for use in combination with radiotherapy for CNS tumors as a normal tissue radioprotectant and for hematopoietoc recovery following whole-body irradiation. This study was undertaken to determine the potential of minocycline as a radioprotective agent of the hematopoietic system and CNS in response to whole-body irradiation with 1, 2 and 3 Gy (γ-rays). C57BL/6 mice were injected with minocycline, 5 times beginning immediately before irradiation. Spleen, blood and brain were collected on days 4 and 32 post-irradiation. WBC and other cell populations were determined in the blood and spleen while cytokines were quantified in CD3-activated splenocytes and homogenized brain supernatants. We also evaluated the impact of minocycline on DNA synthesis and viability of human glioblastoma cells versus astrocytes and microglia. Minocycline increased counts and percentages of splenic macrophages, granulocytes, natural killer (NK), T and CD8 + T cells on day 4 and B cells on day 32. Minocycline up-regulated interleukin-1α (IL-1α)which is radioprotective, as well as

DOMINO, doxycycline 40 mg vs. minocycline 100 mg in the treatment of rosacea: a randomized, single-blinded, noninferiority trial, comparing efficacy and safety.

PubMed

van der Linden, M M D; van Ratingen, A R; van Rappard, D C; Nieuwenburg, S A; Spuls, Ph I

2017-06-01

There is a lack of evidence for minocycline in the treatment of rosacea. To compare the efficacy and safety of doxycycline 40 mg vs. minocycline 100 mg in papulopustular rosacea. In this randomized, single-centre, 1 : 1 allocation, assessor-blinded, noninferiority trial, patients with mild-to-severe papulopustular rosacea were randomly allocated to either oral doxycycline 40 mg or minocycline 100 mg for a 16-week period with 12 weeks of follow-up. Our primary outcomes were the change in lesion count and change in patient's health-related quality of life (using RosaQoL). Intention-to-treat and per protocol analyses were performed. Of the 80 patients randomized (40 minocycline, 40 doxycycline), 71 were treated for 16 weeks. Sixty-eight patients completed the study. At week 16, the median change in lesion count was comparable in both groups: doxycycline vs. minocycline, respectively 13 vs. 14 fewer lesions. The RosaQoL scores were decreased for both doxycycline and minocycline, respectively by 0·62 and 0·86. Secondary outcomes were comparable except for Investigator's Global Assessment success, which was seen significantly more often in the minocycline group than in the doxycycline group (60% vs. 18%, P < 0·001). At week 28, outcomes were comparable, except for RosaQoL scores and PaGA, which were significantly different in favour of minocycline (P = 0·005 and P = 0·043, respectively), and fewer relapses were recorded in the minocycline group than in the doxycycline group (7% and 48%, respectively; P < 0·001). No serious adverse reactions were reported. Minocycline 100 mg is noninferior to doxycycline 40 mg in efficacy over a 16- week treatment period. At follow-up, RosaQoL and PaGA were statistically significantly more improved in the minocycline group than in the doxycycline group, and minocycline 100 mg gives longer remission. In this study there was no significant difference in safety between these treatments; however, based on previous

Early post-stressor intervention with minocycline, a second-generation tetracycline, attenuates post-traumatic stress response in an animal model of PTSD.

PubMed

Levkovitz, Yechiel; Fenchel, Daphna; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

2015-01-01

We assessed the effects of minocycline, a tetracycline with anti-inflammatory, anti-apoptotic and neuroprotective capacities, in an animal model of post-traumatic stress disorder (PTSD). Rats were exposed to psychogenic stress and treated 1h later with minocycline or saline. Behavioral measures included the elevated plus-maze (EPM) and acoustic startle response (ASR) 7 days post stress-exposure. One day after behavioral testing, animals were exposed to a trauma cue and freezing response was assessed. Local levels of cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the hippocampus, frontal cortex (FC) and hypothalamus were then examined. Minocycline attenuated anxious-like behaviors in stress-exposed rats. In addition, decreased levels of cytokines were measured in exposed rats treated with minocycline compared to their counterparts treated with saline. This study suggests a potential use of minocycline in preventing physiological and behavioral alternations resulting from acute exposure to psychological stress. As this is the first study to report beneficial outcomes for minocycline treatment in an animal model of PTSD, further investigations of the use of minocycline in stress-related conditions with emphasis on PTSD is needed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Minocycline is effective in intracerebral hemorrhage by inhibition of apoptosis and autophagy.

PubMed

Wu, Zehan; Zou, Xiang; Zhu, Wei; Mao, Ying; Chen, Liang; Zhao, Fan

2016-12-15

Intracerebral hemorrhage is the least treatable type of stroke and affects millions of people worldwide. Treatment for ICH varies from medicine to surgery, but the rate of mortality and mobility still remains high. Minocycline is a tetracycline antibiotic increasingly recognized for its neuroprotective potential. In earlier studies, we demonstrated that many secondary injuries caused by ICH could be significantly reduced by injection of minocycline in rat models. The following research investigates the role of minocycline in reducing brain injury. Twenty-four rats were administered 100μl autologous arterial blood injections into the right basal ganglia, treated with minocycline or vehicle and euthanized on the 1st, 3rd, and 7th day. Immunohistochemistry, TUNEL, and western blot analysis were performed to analyze the effects of minocycline on apoptosis and autophagy. After the injection of minocycline, TUNEL-positive cells were remarkably reduced on days 1, 3 and 7; Beclin-1, LC3BII/I, caspase-3/8 were all suppressed after treatment. The relationship between Cathepsin D and minocycline remained unknown. Our studies suggest the potential medicinal value of minocycline, through both anti-autophagy and anti-apoptosis pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

Complete resolution of minocycline pigmentation following a single treatment with non-ablative 1550-nm fractional resurfacing in combination with the 755-nm Q-switched alexandrite laser.

PubMed

Vangipuram, Ramya K; DeLozier, Whitney L; Geddes, Elizabeth; Friedman, Paul M

2016-03-01

Pigmentation secondary to minocycline ingestion is an uncommon adverse event affecting 3.7-14.8% of treated individuals for which few effective therapies are available. Three patterns of minocycline pigmentation have a characteristic clinical and histological appearance. The pigment composition in each variety is different and occurs at varying skin depths. Accordingly, a tailored approach according to the type of minocycline pigmentation is crucial for treatment success. The purpose of this intervention was to evaluate the efficacy of non-ablative fractional photothermolysis in combination with the Q-switched alexandrite laser for the treatment of type I minocycline pigmentation on the face. A patient with type I minocycline pigmentation was treated with non-ablative 1550-nm fractional photothermolysis followed immediately by 755-nm Q-switched alexandrite laser and then observed clinically to determine the outcome of this modality. The patient was seen in clinic 1 month later following her single treatment session and 100% clearance of all blue facial pigment was observed. Non-ablative fractional photothermolysis in combination with the 755-nm Q-switched alexandrite laser should be considered for treatment of type I minocycline pigmentation. © 2015 Wiley Periodicals, Inc.

Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor.

PubMed

Amini-Khoei, Hossein; Kordjazy, Nastaran; Haj-Mirzaian, Arya; Amiri, Shayan; Haj-Mirzaian, Arvin; Shirzadian, Armin; Hasanvand, Amin; Balali-Dehkordi, Shima; Hassanipoor, Mahsa; Dehpour, Ahmad Reza

2018-03-20

Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures in mouse considering the possible role of nitric oxide (NO)/NMDA pathway. We induced seizure using intravenous administration of PTZ. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of sub-effective doses of the non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10 mg/kg) and the neuronal NOS inhibitor, 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of sub-effective dose of minocycline (40 mg/kg). We found that inducible NOS inhibitor, aminoguanidine (100 mg/kg), had no effect on the anti-seizure effect of minocycline. Moreover, L-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with NMDA receptor antagonists, ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of sub-effective dose of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of nNOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

Minocycline and Doxycycline, but not Tetracycline, Mitigate Liver and Kidney Injury after Hemorrhagic Shock/Resuscitation*

PubMed Central

Kholmukhamedov, Andaleb; Czerny, Christoph; Hu, Jiangting; Schwartz, Justin; Zhong, Zhi; Lemasters, John J.

2014-01-01

Background Despite recovery of hemodynamics by fluid resuscitation after hemorrhage, development of the systemic inflammatory response and multiple organ dysfunction syndromes can nonetheless lead to death. Minocycline and doxycycline are tetracycline derivatives that are protective in models of hypoxic, ischemic and oxidative stress. Our Aim was to determine whether minocycline and doxycycline protect liver and kidney and improve survival in a mouse model of hemorrhagic shock and resuscitation. Methods Mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood followed by half the shed volume of lactated Ringer's solution containing tetracycline (10 mg/kg), minocycline (10 mg/kg), doxycycline (5 mg/kg) or vehicle. For pre-plus post-treatment, drugs were administered intraperitoneally prior to hemorrhage followed by second equal dose in Ringer's solution after blood resuscitation. Blood and tissue were harvested after 6 h. Results Serum alanine aminotransferase (ALT) increased to 1988 and 1878 U/L after post-treatment with vehicle and tetracycline, respectively, whereas minocycline and doxycycline post-treatment decreased ALT to 857 and 863 U/L. Pre-plus post-treatment with minocycline and doxycycline also decreased ALT to 849 and 834 U/L. After vehicle, blood creatinine increased to 279 μM, which minocycline and doxycycline post-treatment decreased to 118 and 112 μM. Minocycline and doxycycline pre- plus post-treatment decreased creatinine similarly. Minocycline and doxycycline also decreased necrosis and apoptosis in liver and apoptosis in both liver and kidney, the latter assessed by TUNEL and caspase-3 activation. Lastly after 4.5 h of hemorrhage followed by resuscitation, minocycline and doxycycline (but not tetracycline) post-treatment improved 1-week survival from 38%(vehicle) to 69% and 67%, respectively. Conclusion Minocycline and doxycycline were similarly protective when given before as after blood resuscitation and might therefore

Beneficial effects of minocycline on cuprizone induced cortical demyelination.

PubMed

Skripuletz, Thomas; Miller, Elvira; Moharregh-Khiabani, Darius; Blank, Alexander; Pul, Refik; Gudi, Viktoria; Trebst, Corinna; Stangel, Martin

2010-09-01

In this study, we investigated the potential of minocycline to influence cuprizone induced demyelination in the grey and white matter. To induce demyelination C57BL/6 mice were fed with cuprizone for up to 6 weeks and were analysed at different timepoints (week 0, 4, 5, 6). Mice treated with minocycline had less demyelination of the cortex and corpus callosum compared with sham treated animals. In the cortex decreased numbers of activated and proliferating microglia were found after 6 weeks of cuprizone feeding, while there were no significant effects for microglial infiltration of the corpus callosum. In addition to the beneficial effects on demyelination, minocycline prevented from motor coordination disturbance as shown in the beam walking test. For astrogliosis and the numbers of OPC and oligodendrocytes no treatment effects were found. In summary, minocycline treatment diminished the course of demyelination in the grey and white matter and prevented disturbances in motor coordination.

Minocycline attenuates cardiac dysfunction in tumor-burdened mice.

PubMed

Devine, Raymond D; Eichenseer, Clayton M; Wold, Loren E

2016-11-01

Cardiovascular dysfunction as a result of tumor burden is becoming a recognized complication; however, the mechanisms remain unknown. A murine model of cancer cachexia has shown marked increases of matrix metalloproteinases (MMPs), known mediators of cardiac remodeling, in the left ventricle. The extent to which MMPs are involved in remodeling remains obscured. To this end a common antibiotic, minocycline, with MMP inhibitory properties was used to elucidate MMP involvement in tumor induced cardiovascular dysfunction. Tumor-bearing mice showed decreased cardiac function with reduced posterior wall thickness (PWTs) during systole, increased MMP and collagen expression consistent with fibrotic remodeling. Administration of minocycline preserved cardiac function in tumor bearing mice and decreased collagen RNA expression in the left ventricle. MMP protein levels were unaffected by minocycline administration, with the exception of MMP-9, indicating minocycline inhibition mechanisms are directly affecting MMP activity. Cancer induced cardiovascular dysfunction is an increasing concern; novel therapeutics are needed to prevent cardiac complications. Minocycline is a well-known antibiotic and recently has been shown to possess MMP inhibitory properties. Our findings presented here show that minocycline could represent a novel use for a long established drug in the prevention and treatment of cancer induced cardiovascular dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Minocycline attenuates noise-induced hearing loss in rats.

PubMed

Zhang, Jing; Song, Yong-Li; Tian, Ke-Yong; Qiu, Jian-Hua

2017-02-03

Noise-induced hearing loss (NIHL) is a serious health concern and prevention of hair cell death or therapeutic intervention at the early stage of NIHL is critical to preserve hearing. Minocycline is a semi-synthetic derivative of tetracycline and has been shown to have otoprotective effects in ototoxic drug-induced hearing impairment, however, whether minocycline can protect against NIHL has not been investigated. The present study demonstrated elevated ABR (auditory brainstem response) thresholds and outer hair cell loss following traumatic noise exposure, which was mitigated by intraperitoneal administration of minocycline (45mg/kg/d) for 5 consecutive days. In conclusion, the present study demonstrated that minocycline, a clinically approved drug with a good safety profile, can attenuate NIHL in rats and may potentially be used for treatment of hearing loss in clinic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

PubMed Central

Hanlon, Lauren A.; Huh, Jimmy W.

2016-01-01

Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

Resolution of radiation-induced acneform eruption following treatment with tretinoin and minocycline: a case report.

PubMed

Parr, Karina; Mahmoudizad, Rod; Grimwood, Ronald

2013-07-01

Postradiation comedogenesis is an uncommon side effect of radiation therapy, with few cases reported in the medical literature. The proposed etiology of this reaction is alteration of pilosebaceous unit secretions and retention of proliferating ductal keratinocytes due to stricture and scarring. We report a case of a 48-year-old woman who had been treated for infiltrating ductal carcinoma of the right breast with lumpectomy and radiation therapy. She subsequently developed open and closed comedones as well as tender inflammatory papules and papulopustules in the irradiated area. Our patient was treated with tretinoin cream and oral minocycline, with rapid improvement in symptoms and complete resolution of lesions after 2 months of therapy. We review the literature on the pathogenesis, clinical features, and treatment of postradiation acne, and discuss rapid resolution of a radiation-induced acneform eruption after combination treatment with tretinoin and minocycline.

Minocycline blocks glial cell activation and ventilatory acclimatization to hypoxia

PubMed Central

Arbogast, Tara E.; Moya, Esteban A.; Fu, Zhenxing; Powell, Frank L.

2017-01-01

Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague-Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg ip daily) or saline beginning 1 day before and during 7 days of chronic hypoxia (CH, PiO2 = 70 Torr). Minocycline had no effect on normoxic control rats or the hypercapnic ventilatory response in CH rats, but minocycline significantly (P < 0.001) decreased ventilation during acute hypoxia in CH rats. However, minocycline administration during only the last 3 days of CH did not reverse VAH. Microglia and astrocyte activation in the nucleus tractus solitarius was quantified from 30 min to 7 days of CH. Microglia showed an active morphology (shorter and fewer branches) after 1 h of hypoxia and returned to the control state (longer filaments and extensive branching) after 4 h of CH. Astrocytes increased glial fibrillary acidic protein antibody immunofluorescent intensity, indicating activation, at both 4 and 24 h of CH. Minocycline had no effect on glia in normoxia but significantly decreased microglia activation at 1 h of CH and astrocyte activation at 24 h of CH. These results support a role for glial cells, providing an early signal for the induction but not maintenance of neural plasticity underlying ventilatory acclimatization to hypoxia. NEW & NOTEWORTHY The signals for neural plasticity in medullary respiratory centers underlying ventilatory acclimatization to chronic hypoxia are unknown. We show that chronic hypoxia activates microglia and subsequently astrocytes. Minocycline, an antibiotic that blocks microglial activation and has anti

Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial

PubMed Central

Savitz, Jonathan; Preskorn, Sheldon; Teague, T Kent; Drevets, Douglas; Yates, William

2012-01-01

Introduction New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence suggests that BD is characterised by neural changes such as dendritic remodelling and glial and neuronal cell loss. These changes have been hypothesised to result from chronic inflammation. The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug with neuroprotective and immune-modulating properties, and of aspirin, at doses expected to selectively inhibit cyclooxygenase 1 (COX-1). Methods and analysis 120 outpatients between 18 and 55 years of age, who meet DSM-IV-TR criteria for BD (type I or II) and for a current major depressive episode will be recruited to take part in a randomised, double-blind, placebo-controlled, parallel-group, proof-of-concept clinical trial following a 2×2 design. As adjuncts to existing treatment, subjects will be randomised to receive one of the four treatment combinations: placebo-minocycline plus placebo-aspirin, active-minocycline plus placebo-aspirin, placebo-minocycline plus active-aspirin or active-minocycline plus active-aspirin. The dose of minocycline and aspirin is 100 mg twice daily and 81 mg twice daily, respectively. Antidepressant response will be evaluated by assessing changes in the Montgomery–Asberg Depression Rating Scale scores between baseline and the end of the 6-week trial. As secondary outcome measures, the anti-inflammatory effects of minocycline and aspirin will be tested by measuring pre-treatment and post-treatment levels of C reactive protein and inflammatory cytokines. Ethics and dissemination Minocycline has been widely used as an antibiotic in doses up to 400 mg/day. Low-dose aspirin has been safely used on a worldwide scale for its role as an antithrombotic and thrombolytic. The study progress will be overseen by a Data, Safety and Monitoring Board, which will meet once every

Long-lasting Effects of Minocycline on Behavior in Young but not Adult Fragile X Mice

PubMed Central

Dansie, Lorraine E.; Phommahaxay, Kelly; Okusanya, Ayodeji G.; Uwadia, Jessica; Huang, Mike; Rotschafer, Sarah E.; Razak, Khaleel A.; Ethell, Douglas W.; Ethell, Iryna M.

2013-01-01

Fragile X Syndrome (FXS) is the most common single-gene inherited form of intellectual disability with behaviors characteristic of autism. People with FXS display childhood seizures, hyperactivity, anxiety, developmental delay, attention deficits, and visual-spatial memory impairment, as well as a propensity for obsessive-compulsive disorder (OCD). Several of these aberrant behaviors and FXS-associated synaptic irregularities also occur in “fragile X mental retardation gene” knock-out (Fmr1 KO) mice. We previously reported that minocycline promotes the maturation of dendritic spines - postsynaptic sites for excitatory synapses - in the developing hippocampus of Fmr1 KO mice, which may underlie the beneficial effects of minocycline on anxiolytic behavior in young Fmr1 KO mice. In this study, we compared the effectiveness of minocycline treatment in young and adult Fmr1 KO mice, and determined the dependence of behavioral improvements on short-term versus long-term minocycline administration. We found that 4 and 8 week long treatments significantly reduced locomotor activity in both young and adult Fmr1 KO mice. Some behavioral improvements persisted in young mice post-treatment, but in adults the beneficial effects were lost soon after minocycline treatment was stopped. We also show, for the first time, that minocycline treatment partially attenuates the number and severity of audiogenic seizures in Fmr1 KO mice. This report provides further evidence that minocycline treatment has immediate and long-lasting benefits on FXS-associated behaviors in the Fmr1 KO mouse model. PMID:23660195

Minocycline as Adjunctive Treatment to Risperidone in Children with Autistic Disorder: A Randomized, Double-Blind Placebo-Controlled Trial.

PubMed

Ghaleiha, Ali; Alikhani, Rosa; Kazemi, Mohammad-Reza; Mohammadi, Mohammad-Reza; Mohammadinejad, Payam; Zeinoddini, Atefeh; Hamedi, Mehdi; Shahriari, Mona; Keshavarzi, Zahra; Akhondzadeh, Shahin

2016-11-01

This is an investigation of minocycline efficacy and safety as an adjuvant to risperidone in management of children with autism. Forty-six children with diagnosis of autistic disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale, who were already drug-free for at least 6 months participated in a randomized controlled trial and underwent 10 weeks of treatment with either minocycline (50 mg twice per day) or placebo in addition to risperidone titrated up to 2 mg/day (based on bodyweight). Patients were evaluated using ABC-C at baseline and at weeks 5 and 10. General linear model repeated measures showed significant effect for time × treatment interaction on the irritability [F(2, 88) = 3.94, p = 0.02] and hyperactivity/noncompliance [F(1.50, 66.05) = 7.92, p = 0.002], but not for lethargy/social withdrawal [F(1.61, 71.02) = 0.98, p = 0.36], stereotypic behavior [F(1.34, 58.80) = 1.55, p = 0.22], and inappropriate speech subscale scores [F(1.52, 66.88) = 1.15, p = 0.31]. By week 10, 21 (91.3%) patients in the minocycline group and 15 (65.5%) patients in the placebo group achieved at least partial response (p = 0.03). Frequencies of adverse events were not significantly different between groups. Minocycline seems to be a safe and effective adjuvant in management of patients with autistic disorder. Future studies with larger sample sizes, longer follow-ups, and inflammatory cytokine measurements are warranted to confirm these findings and provide insight into minocycline mechanism of action in autistic disorder.

Topical Minocycline Effectively Decontaminates and Reduces Inflammation in Infected Porcine Wounds.

PubMed

Daly, Lauren Tracy; Tsai, David M; Singh, Mansher; Nuutila, Kristo; Minasian, Raquel A; Lee, Cameron C Y; Kiwanuka, Elizabeth; Hackl, Florian; Onderdonk, Andrew B; Junker, Johan P E; Eriksson, Elof; Caterson, Edward J

2016-11-01

Wound infection can impair postoperative healing. Topical antibiotics have potential to treat wound infection and inflammation and minimize the adverse effects associated with systemic antibiotics. Full-thickness porcine wounds were infected with Staphylococcus aureus. Using polyurethane wound enclosure devices, wounds were treated with topical 100 μg/ml minocycline, topical 1000 μg/ml minocycline, topical saline control, or 4 mg/kg intravenous minocycline. Bacteria were quantified in wound tissue and fluid obtained over 9 hours. Immunosorbent assays were used to analyze inflammatory marker concentrations. Minocycline's effect on in vitro migration and proliferation of human keratinocytes and fibroblasts was tested using scratch assays and metabolic assays, respectively. After 6 hours, 100 and 1000 μg/ml topical minocycline decreased bacteria in wound tissue to 3.5 ± 0.87 and 2.9 ± 2.3 log colony-forming units/g respectively, compared to 8.3 ± 0.9 log colony-forming units/g in control wounds (p < 0.001) and 6.9 ± 0.2 log colony-forming units/g in wounds treated with 4 mg/kg intravenous minocycline (p < 0.01). After 2 hours, topical minocycline reduced concentrations of the inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α (p < 0.01), and inflammatory cell counts in wound tissue (p < 0.05). In noninfected wounds, topical minocycline significantly reduced interleukin-1β, interleukin-6, and inflammatory cell counts after 4 hours (p < 0.01). Matrix metalloproteinase-9 concentrations decreased after 1-hour treatment (p < 0.05). Keratinocyte and fibroblast in vitro functions were not adversely affected by 10 μg/ml minocycline or less. Topical minocycline significantly reduces bacterial burden and inflammation in infected wounds compared with wounds treated with intravenous minocycline or control wounds. Minocycline also decreases local inflammation independently of its antimicrobial effect.

Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

PubMed Central

Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H.; Ogbi, Safia N.; Fagan, Susan C.

2013-01-01

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

Minocycline attenuates sevoflurane-induced cell injury via activation of Nrf2

PubMed Central

Tian, Yue; Wu, Xiuying; Guo, Shanbin; Ma, Ling; Huang, Wei; Zhao, Xiaochun

2017-01-01

Minocycline has been demonstrated to exert neuroprotective effects in various experimental models. In the present study, we investigated the mechanisms underlying the protective effects of minocycline on cell injury induced by the inhalation of the anesthetic, sevoflurane. In our in vivo experiments using rats, minocycline attenuated sevoflurane-induced neuronal degeneration and apoptosis in the rat hippocampus, and this effect was associated with the minocycline-mediated suppression of oxidative stress in the hippocampus. In in vitro experiments, minocycline inhibited sevoflurane-induced apoptosis and the production of reactive oxygen species (ROS) in H4 human neuroglioma cells. In addition, minocycline suppressed the sevoflurane-induced upregulation of interleukin (IL)-6 and the activation of the nuclear factor-κB (NF-κB) signaling pathway in H4 cells. Furthermore, we found that nuclear factor E2-related factor 2 (Nrf2), an activator of the stress response, was upregulated and activated upon sevoflurane treatment both in the rat hippocampus and in H4 cells. In addition, minocycline further augmented the upregulation and activation of Nrf2 when used in conjunction with sevoflurane. Moreover, the knockdown of Nrf2 in H4 cells by small interfering RNA (siRNA) diminished the cytoprotective effect of minocycline, and attenuated the inhibitory effect of minocycline on ROS production, IL-6 upregulation and the activation of the NF-κB signaling pathway. On the whole, our findings indicate that minocycline may exert protective effects against sevoflurane-induced cell injury via the Nrf2-modulated antioxidant response and the inhibition of the activation of the NF-κB signaling pathway. PMID:28260081

Differential effects of minocycline on microglial activation and neurodegeneration following closed head injury in the neonate rat

PubMed Central

Hanlon, L.A.; Raghupathi, R.; Huh, J.W.

2017-01-01

The role of microglia in the pathophysiology of injury to the developing brain has been extensively studied. In children under the age of 4 who have sustained a traumatic brain injury (TBI), markers of microglial/macrophage activation were increased in the cerebrospinal fluid and were associated with worse neurologic outcome. Minocycline is an antibiotic that decreases microglial/macrophage activation following hypoxic-ischemia in neonatal rodents and TBI in adult rodents thereby reducing neurodegeneration and behavioral deficits. In study 1, 11-day-old rats received an impact to the intact skull and were treated for 3 days with minocycline. Immediately following termination of minocycline administration, microglial reactivity was reduced in the cortex and hippocampus (p<0.001) and was accompanied by an increase in the number of fluoro-Jade B profiles (p<0.001) suggestive of a reduced clearance of degenerating cells; however, this effect was not sustained at 7 days post-injury. Although microglial reactivity was reduced in the white matter tracts (p<0.001), minocycline treatment did not reduce axonal injury or degeneration. In the thalamus, minocycline treatment did not affect microglial reactivity, axonal injury and degeneration, and neurodegeneration. Injury-induced spatial learning and memory deficits were also not affected by minocycline. In study 2, to test whether extended dosing of minocycline may be necessary to reduce the ongoing pathologic alterations, a separate group of animals received minocycline for 9 days. Immediately following termination of treatment, microglial reactivity and neurodegeneration in all regions examined were exacerbated in minocycline-treated brain-injured animals compared to brain-injured animals that received vehicle (p<0.001), an effect that was only sustained in the cortex and hippocampus up to 15 days post-injury (p<0.001). Whereas injury-induced spatial learning deficits remained unaffected by minocycline treatment, memory

Differential effects of minocycline on microglial activation and neurodegeneration following closed head injury in the neonate rat.

PubMed

Hanlon, L A; Raghupathi, R; Huh, J W

2017-04-01

The role of microglia in the pathophysiology of injury to the developing brain has been extensively studied. In children under the age of 4 who have sustained a traumatic brain injury (TBI), markers of microglial/macrophage activation were increased in the cerebrospinal fluid and were associated with worse neurologic outcome. Minocycline is an antibiotic that decreases microglial/macrophage activation following hypoxic-ischemia in neonatal rodents and TBI in adult rodents thereby reducing neurodegeneration and behavioral deficits. In study 1, 11-day-old rats received an impact to the intact skull and were treated for 3days with minocycline. Immediately following termination of minocycline administration, microglial reactivity was reduced in the cortex and hippocampus (p<0.001) and was accompanied by an increase in the number of fluoro-Jade B profiles (p<0.001) suggestive of a reduced clearance of degenerating cells; however, this effect was not sustained at 7days post-injury. Although microglial reactivity was reduced in the white matter tracts (p<0.001), minocycline treatment did not reduce axonal injury or degeneration. In the thalamus, minocycline treatment did not affect microglial reactivity, axonal injury and degeneration, and neurodegeneration. Injury-induced spatial learning and memory deficits were also not affected by minocycline. In study 2, to test whether extended dosing of minocycline may be necessary to reduce the ongoing pathologic alterations, a separate group of animals received minocycline for 9days. Immediately following termination of treatment, microglial reactivity and neurodegeneration in all regions examined were exacerbated in minocycline-treated brain-injured animals compared to brain-injured animals that received vehicle (p<0.001), an effect that was only sustained in the cortex and hippocampus up to 15days post-injury (p<0.001). Whereas injury-induced spatial learning deficits remained unaffected by minocycline treatment, memory

Minocycline: far beyond an antibiotic

PubMed Central

Garrido-Mesa, N; Zarzuelo, A; Gálvez, J

2013-01-01

Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein. PMID:23441623

Minocycline blocks glial cell activation and ventilatory acclimatization to hypoxia.

PubMed

Stokes, Jennifer A; Arbogast, Tara E; Moya, Esteban A; Fu, Zhenxing; Powell, Frank L

2017-04-01

Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague-Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg ip daily) or saline beginning 1 day before and during 7 days of chronic hypoxia (CH, Pi O 2  = 70 Torr). Minocycline had no effect on normoxic control rats or the hypercapnic ventilatory response in CH rats, but minocycline significantly ( P < 0.001) decreased ventilation during acute hypoxia in CH rats. However, minocycline administration during only the last 3 days of CH did not reverse VAH. Microglia and astrocyte activation in the nucleus tractus solitarius was quantified from 30 min to 7 days of CH. Microglia showed an active morphology (shorter and fewer branches) after 1 h of hypoxia and returned to the control state (longer filaments and extensive branching) after 4 h of CH. Astrocytes increased glial fibrillary acidic protein antibody immunofluorescent intensity, indicating activation, at both 4 and 24 h of CH. Minocycline had no effect on glia in normoxia but significantly decreased microglia activation at 1 h of CH and astrocyte activation at 24 h of CH. These results support a role for glial cells, providing an early signal for the induction but not maintenance of neural plasticity underlying ventilatory acclimatization to hypoxia. NEW & NOTEWORTHY The signals for neural plasticity in medullary respiratory centers underlying ventilatory acclimatization to chronic hypoxia are unknown. We show that chronic hypoxia activates microglia and subsequently astrocytes. Minocycline, an antibiotic that blocks microglial activation and has anti

Early Minocycline and Late FK506 Treatment Improves Survival and Alleviates Neuroinflammation, Neurodegeneration, and Behavioral Deficits in Prion-Infected Hamsters.

PubMed

Shah, Syed Zahid Ali; Zhao, Deming; Taglialatela, Giulio; Khan, Sher Hayat; Hussain, Tariq; Dong, Haodi; Lai, Mengyu; Zhou, Xiangmei; Yang, Lifeng

2017-04-01

Prion infections of the central nervous system (CNS) are characterized by initial reactive gliosis followed by overt neuronal death. Gliosis is likely to be caused initially by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrP Sc ) of the normal cellular prion protein (PrP c ) in the brain. Proinflammatory cytokines and chemokines released by PrP Sc -activated glia and stressed neurons may also contribute directly or indirectly to the disease development by enhancing gliosis and inducing neurotoxicity. Recent studies have illustrated that early neuroinflammation activates nuclear factor of activated T cells (NFAT) in the calcineurin signaling cascade, resulting in nuclear translocation of nuclear factor kappa B (NF-κB) to promote apoptosis. Hence, useful therapeutic approaches to slow down the course of prion disease development should control early inflammatory responses to suppress NFAT signaling. Here we used a hamster model of prion diseases to test, for the first time, the neuroprotective and NFAT-suppressive effect of a second-generation semisynthetic tetracycline derivative, minocycline, versus a calcineurin inhibitor, FK506, with known NFAT suppressive activity. Our results indicate that prolonged treatment with minocycline, starting from the presymptomatic stage of prion disease was more effective than FK506 given either during the presymptomatic or symptomatic stage of prion disease. Specifically, minocycline treatment reduced the expression of the astrocyte activation marker glial fibrillary acidic protein and of the microglial activation marker ionized calcium-binding adapter molecule-1, subsequently reducing the level of proinflammatory cytokines interleukin 1β and tumor necrosis factor-α. We further found that minocycline and FK506 treatment inhibited mitogen-activated protein kinase p38 phosphorylation and NF-κB nuclear translocation in a caspase-dependent manner, and enhanced phosphorylated cyclic adenosine monophosphate

Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment.

PubMed

Chaudhry, Imran B; Hallak, Jaime; Husain, Nusrat; Minhas, Fareed; Stirling, John; Richardson, Paul; Dursun, Serdar; Dunn, Graham; Deakin, Bill

2012-09-01

The onset and early course of schizophrenia is associated with subtle loss of grey matter which may be responsible for the evolution and persistence of symptoms such as apathy, emotional blunting, and social withdrawal. Such 'negative' symptoms are unaffected by current antipsychotic therapies. There is evidence that the antibiotic minocycline has neuroprotective properties. We investigated whether the addition of minocycline to treatment as usual (TAU) for 1 year in early psychosis would reduce negative symptoms compared with placebo. In total, 144 participants within 5 years of first onset in Brazil and Pakistan were randomised to receive TAU plus placebo or minocycline. The primary outcome measures were the negative and positive syndrome ratings using the Positive and Negative Syndrome Scale. Some 94 patients completed the trial. The mean improvement in negative symptoms for the minocycline group was 9.2 and in the placebo group 4.7, an adjusted difference of 3.53 (s.e. 1.01) 95% CI: 1.55, 5.51; p < 0.001 in the intention-to-treat population. The effect was present in both countries. The addition of minocycline to TAU early in the course of schizophrenia predominantly improves negative symptoms. Whether this is mediated by neuroprotective, anti-inflammatory or others actions is under investigation.

Comparative pharmacokinetics of minocycline in foals and adult horses.

PubMed

Giguère, S; Burton, A J; Berghaus, L J; Haspel, A D

2017-08-01

The objective of this study was to compare the pharmacokinetics of minocycline in foals vs. adult horses. Minocycline was administered to six healthy 6- to 9-week-old foals and six adult horses at a dose of 4 mg/kg intragastrically (IG) and 2 mg/kg intravenously (i.v.) in a cross-over design. Five additional oral doses were administered at 12-h intervals in foals. A microbiologic assay was used to measure minocycline concentration in plasma, urine, synovial fluid, and cerebrospinal fluid (CSF). Liquid chromatography-tandem mass spectrometry was used to measure minocycline concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar (BAL) cells. After i.v. administration to foals, minocycline had a mean (±SD) elimination half-life of 8.5 ± 2.1 h, a systemic clearance of 113.3 ± 26.1 mL/h/kg, and an apparent volume of distribution of 1.24 ± 0.19 L/kg. Pharmacokinetic variables determined after i.v. administration to adult horses were not significantly different from those determined in foals. Bioavailability was significantly higher in foals (57.8 ± 19.3%) than in adult horses (32.0 ± 18.0%). Minocycline concentrations in PELF were higher than in other body fluids. Oral minocycline dosed at 4 mg/kg every 12 h might be adequate for the treatment of susceptible bacterial infections in foals. © 2016 John Wiley & Sons Ltd.

Minocycline increases the life span and motor activity and decreases lipid peroxidation in manganese treated Drosophila melanogaster.

PubMed

Bonilla, E; Contreras, R; Medina-Leendertz, S; Mora, M; Villalobos, V; Bravo, Y

2012-03-29

The objective of this study was to investigate the effect of Minocycline in the life span, motor activity, and lipid peroxidation of Drosophila melanogaster treated with manganese. Two days after emerging from the pupa male wild-type D. melanogaster were fed for 13 days with corn media containing 15 mM manganese. Then, they were divided in six groups of 300 flies each: group (a) remained treated with manganese (Mn group); group (b) began treatment with Minocycline (0.05 mM) (Mn-Minocycline group); group (c) received no additional treatment (Mn-no treatment group); group (d) simultaneously fed with manganese and Minocycline (Mn+Minocycline group). Additionally, a control (group e) with no treatment and another group (f) fed only with Minocycline after emerging from the pupa were added. All the manganese treated flies (group a) were dead on the 25th day. The life span in group f (101.66±1.33 days, mean S.E.M.) and of group b (97.00±3.46 days) were similar, but in both cases it was significantly higher than in group e (68.33±1.76 days), group c (67.05±2.30 days) and in those of group d (37.33±0.88). Manganese (groups a and d) decreased motor activity in D. melanogaster. In the Minocycline fed flies (groups b and f) a higher motor activity was detected. In Mn-Minocycline and Mn+Minocycline treated flies a significant decrease of MDA levels was detected when compared to the Minocycline group indicating that Minocycline and Mn appear to have a synergistic effect. In conclusion, Minocycline increased the life span and motor activity and decreased MDA formation of manganese treated D. melanogaster, probably by an inhibition of the production of reactive oxygen species. Manganese also exerted an antioxidant effect as shown by the significant decrease of MDA levels when compared to control flies. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Minocycline attenuates the development of diabetic neuropathy by inhibiting spinal cord Notch signaling in rat.

PubMed

Yang, Cheng; Gao, Jie; Wu, Banglin; Yan, Nuo; Li, Hui; Ren, Yiqing; Kan, Yufei; Liang, Jiamin; Jiao, Yang; Yu, Yonghao

2017-10-01

We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord. Minocycline treatment, however, accelerated the decreased conduction velocity of sciatic nerve and suppressed Notch-1expression and activity in diabetic rats. Similar to DAPT treatment, minocycline administration also prolonged thermal withdrawal latency (TWL) and increase mechanical withdrawal threshold (MWT) in diabetic rats in response to heat or mechanical stimulation via inhibition the expression and the activity of Notch-1 in spinal cord. Combination of DAPT and minocycline further inhibited Notch-1 receptor signaling and reduce neuropathic pain exhibited as improved TWL and MWT. Our study revealed a novel mechanism of Notch-1 receptor inhibition in spinal cord induced by minocycline administration, and suggested that the combination of minocycline and DAPT has the potential to treat DNP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Adjunctive minocycline for schizophrenia: A meta-analysis of randomized controlled trials.

PubMed

Xiang, Ying-Qiang; Zheng, Wei; Wang, Shi-Bin; Yang, Xin-Hu; Cai, Dong-Bin; Ng, Chee H; Ungvari, Gabor S; Kelly, Deanna L; Xu, Wei-Ying; Xiang, Yu-Tao

2017-01-01

This study aimed to conduct a meta-analysis of the efficacy and safety of adjunctive minocycline for schizophrenia. Randomized controlled trials (RCTs) comparing adjunctive minocycline with placebo in patients with schizophrenia were included in the meta-analysis. Two independent investigators extracted and synthesized data. Standard mean differences (SMDs), risk ratio (RR) ±95% confidence intervals (CIs) and the number-needed-to-harm (NNH) were calculated. Eight RCTs with 548 schizophrenia patient including 286 (52.2%) patients on minocycline (171.9±31.2mg/day) and 262 (47.8%) on placebo completed 18.5±13.4 weeks of treatment. Meta-analyses of Positive and Negative Syndrome Scale (PANSS) (7 RCTs with 8 treatment arms)/Brief Psychiatric Rating Scale (BPRS) (1 RCT) total score [SMD: -0.64, (95%CI: -1.02, -0.27), P=0.0008; I 2 =74%], positive, negative and general symptom scores [SMD: -0.69 to -0.22 (95%CI: -0.98, -0.03), P=0.02-0.00001; I 2 =7-63%] revealed a significant superiority of adjunctive minocycline treatment over the placebo. There was no significant difference regarding neurocognitive function, discontinuation rate and adverse drug reactions between the two groups. This meta-analysis showed that adjunctive minocycline appears to be efficacious and safe for schizophrenia. Due to significant heterogeneity, future studies with a large sample size are needed to confirm these findings. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Minocycline Attenuates Iron-Induced Brain Injury.

PubMed

Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

2016-01-01

Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p < 0.05). The co-injection of minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p < 0.01). Albumin, a marker of BBB disruption, was measured by Western blot analysis. Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p < 0.01). Iron-handling protein levels in the brain, including ceruloplasmin and transferrin, were reduced in the minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.

Minocycline attenuates sevoflurane-induced cell injury via activation of Nrf2.

PubMed

Tian, Yue; Wu, Xiuying; Guo, Shanbin; Ma, Ling; Huang, Wei; Zhao, Xiaochun

2017-04-01

Minocycline has been demonstrated to exert neuroprotective effects in various experimental models. In the present study, we investigated the mechanisms underlying the protective effects of minocycline on cell injury induced by the inhalation of the anesthetic, sevoflurane. In our in vivo experiments using rats, minocycline attenuated sevoflurane-induced neuronal degeneration and apoptosis in the rat hippocampus, and this effect was associated with the minocycline-mediated suppression of oxidative stress in the hippocampus. In in vitro experiments, minocycline inhibited sevoflurane-induced apoptosis and the production of reactive oxygen species (ROS) in H4 human neuroglioma cells. In addition, minocycline suppressed the sevoflurane-induced upregulation of interleukin (IL)-6 and the activation of the nuclear factor-κB (NF-κB) signaling pathway in H4 cells. Furthermore, we found that nuclear factor E2-related factor 2 (Nrf2), an activator of the stress response, was upregulated and activated upon sevoflurane treatment both in the rat hippocampus and in H4 cells. In addition, minocycline further augmented the upregulation and activation of Nrf2 when used in conjunction with sevoflurane. Moreover, the knockdown of Nrf2 in H4 cells by small interfering RNA (siRNA) diminished the cytoprotective effect of minocycline, and attenuated the inhibitory effect of minocycline on ROS production, IL-6 upregulation and the activation of the NF-κB signaling pathway. On the whole, our findings indicate that minocycline may exert protective effects against sevoflurane-induced cell injury via the Nrf2-modulated antioxidant response and the inhibition of the activation of the NF-κB signaling pathway.

Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study.

PubMed

Cukras, Catherine A; Petrou, Philip; Chew, Emily Y; Meyerle, Catherine B; Wong, Wai T

2012-06-22

Inflammation contributes significantly to the pathogenesis of diabetic macular edema (DME). In particular, retinal microglia demonstrate increased activation and aggregation in areas of DME. Study authors investigated the safety and potential efficacy of oral minocycline, a drug capable of inhibiting microglial activation, in the treatment of DME. A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with fovea-involving DME who received oral minocycline 100 mg twice daily for 6 months. Main outcome measurements included best-corrected visual acuity (BCVA), central retinal subfield thickness (CST), and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiography (FA). Findings indicated that the study drug was well tolerated and not associated with significant safety issues. In study eyes, mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0, +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on OCT decreased by -2.9%, -5.7%, -13.9, and -8.1% for the same time points. At month 6, mean area of late leakage on FA decreased by -34.4% in study eyes. Mean changes in contralateral fellow eyes also demonstrated similar trends. Improvements in outcome measures were not correlated with concurrent changes in systemic factors. In this pilot proof-of-concept study of DME, minocycline as primary treatment was associated with improved visual function, central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. Microglial inhibition with oral minocycline may be a promising therapeutic strategy targeting the inflammatory etiology of DME. (ClinicalTrials.gov number, NCT01120899.).

Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B∗35:02 as a risk factor.

PubMed

Urban, Thomas Jacob; Nicoletti, Paola; Chalasani, Naga; Serrano, José; Stolz, Andrew; Daly, Ann K; Aithal, Guruprasad P; Dillon, John; Navarro, Victor; Odin, Joseph; Barnhart, Huiman; Ostrov, David; Long, Nanye; Cirulli, Elizabeth Trilby; Watkins, Paul Brent; Fontana, Robert John

2017-07-01

Minocycline hepatotoxicity can present with prominent autoimmune features in previously healthy individuals. The aim of this study was to identify genetic determinants of minocycline drug-induced liver injury (DILI) in a well-phenotyped cohort of patients. Caucasian patients with minocycline DILI underwent genome-wide genotyping and were compared to unexposed population controls. Human leukocyte antigen (HLA) binding of minocycline was assessed using AutoDock Vina. Among the 25 cases, 80% were female, median age was 19years and median latency from drug start to DILI onset was 318days. At presentation, 76% had acute hepatocellular liver injury, median ALT 1,077U/L (range: 63 to 2,333), median bilirubin 4.5mg/dl (range: 0.2 to 16.7), and 90% had a +ANA. During follow-up, 50% were treated with corticosteroids and no participants died or required a liver transplant. A significant association was noted between HLA-B∗35:02 and risk for minocycline DILI; a 16% carrier frequency in DILI cases compared to 0.6% in population controls (odds ratio: 29.6, 95% CI: 7.8-89.8, p=2.5×10 -8 ). Verification of HLA-B∗35:02 imputation was confirmed by sequence-based HLA typing. HLA-B∗35:02 carriers had similar presenting features and outcomes compared to non-carriers. In silico modeling studies support the hypothesis that direct binding of minocycline to this novel HLA risk allele might be an important initiating event in minocycline DILI. HLA-B∗35:02 is a rare HLA allele that was more frequently identified in the 25 minocycline DILI cases compared to population controls. If confirmed in other cohorts, this HLA allele may prove to be a useful diagnostic marker of minocycline DILI. Development of liver injury following prolonged use of minocycline for acne is a rare but potentially severe form of drug-induced liver injury. Our study demonstrates that individuals who are HLA-B∗35:02 carriers are at increased risk of developing minocycline related liver injury. These results may

Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS

PubMed Central

Campbell, Jennifer H.; Burdo, Tricia H.; Autissier, Patrick; Bombardier, Jeffrey P.; Westmoreland, Susan V.; Soulas, Caroline; González, R. Gilberto; Ratai, Eva-Maria; Williams, Kenneth C.

2011-01-01

Background Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline's functions are not well defined. Methods Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy (1H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied. Results Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14loCD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/Cr (neuronal injury) and circulating CD14+CD16+ and CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation. Conclusion Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation. PMID:21494695

Minocycline Causes Widespread Cell Death and Increases Microglial Labeling in the Neonatal Mouse Brain

PubMed Central

Strahan, J. Alex; Walker, William H.; Montgomery, Taylor R.; Forger, Nancy G.

2016-01-01

Minocycline, an antibiotic of the tetracycline family, inhibits microglia in many paradigms, and is among the most commonly used tools for examining the role of microglia in physiological processes. Microglia may play an active role in triggering developmental neuronal cell death, although findings have been contradictory. To determine whether microglia influence developmental cell death, we treated perinatal mice with minocycline (45 mg/kg) and quantified effects on dying cells and microglial labeling using immunohistochemistry for activated caspase-3 (AC3) and ionized calcium-binding adapter molecule 1 (Iba1), respectively. Contrary to our expectations, minocycline treatment from embryonic day 18 to postnatal day (P)1 caused a >10-fold increase in cell death 8 h after the last injection in all brain regions examined, including the primary sensory cortex (S1), septum, hippocampus and hypothalamus. Iba1 labeling was also increased in most regions. Similar effects, although of smaller magnitude, were seen when treatment was delayed to P3-P5. Minocycline treatment from P3-P5 also decreased overall cell number in the septum at weaning, suggesting lasting effects of the neonatal exposure. When administered at lower doses (4.5 or 22.5 mg/kg), or at the same dose one week later (P10-P12), minocycline no longer increased microglial markers or cell death. Taken together, the most commonly used microglial “inhibitor” increases cell death and Iba1 labeling in the neonatal mouse brain. Minocycline is used clinically in infant and pediatric populations; caution is warrented when using minocycline in developing animals, or extrapolating the effects of this drug across ages. PMID:27706925

Minocycline Suppresses Interleukine-6, Its Receptor System and Signaling Pathways and Impairs Migration, Invasion and Adhesion Capacity of Ovarian Cancer Cells: In Vitro and In Vivo Studies

PubMed Central

Ataie-Kachoie, Parvin; Morris, David L.; Pourgholami, Mohammad H.

2013-01-01

Interleukin (IL)-6 has been shown to be a major contributing factor in growth and progression of ovarian cancer. The cytokine exerts pro-tumorigenic activity through activation of several signaling pathways in particular signal transducer and activator of transcription (STAT3) and extracellular signal-regulated kinase (ERK)1/2. Hence, targeting IL-6 is becoming increasingly attractive as a treatment option in ovarian cancer. Here, we investigated the effects of minocycline on IL-6 and its signaling pathways in ovarian cancer. In vitro, minocycline was found to significantly suppress both constitutive and IL-1β or 4-hydroxyestradiol (4-OH-E2)-stimulated IL-6 expression in human ovarian cancer cells; OVCAR-3, SKOV-3 and CAOV-3. Moreover, minocycline down-regulated two major components of IL-6 receptor system (IL-6Rα and gp130) and blocked the activation of STAT3 and ERK1/2 pathways leading to suppression of the downstream product MCL-1. In female nude mice bearing intraperitoneal OVCAR-3 tumors, acute administration (4 and 24 h) of minocycline (30 mg/kg) led to suppression of IL-6. Even single dose of minocycline was effective at significantly lowering plasma and tumor IL-6 levels. In line with this, tumoral expression of p-STAT3, p-ERK1/2 and MCL-1 were decreased in minocycline-treated mice. Evaluation of the functional implication of minocycline on metastatic activity revealed the capacity of minocycline to inhibit cellular migration, invasion and adhesion associated with down-regulation of matrix metalloproteinases (MMP)-2 and 9. Thus, the data suggest a potential role for minocycline in suppressing IL-6 expression and activity. These effects may prove to be an important attribute to the upcoming clinical trials of minocycline in ovarian cancer. PMID:23593315

Black veins: a case of minocycline-induced pigmentation post-sclerotherapy and a review of literature.

PubMed

Star, Phoebe; Choy, Carolyn; Parsi, Kurosh

2017-01-01

Minocycline-induced pigmentation (MIP) is an uncommon but well-described adverse effect of oral minocycline treatment. MIP is clinically and histopathologically distinct from post-sclerotherapy pigmentation. We report a case of a patient presenting with blackened skin overlying veins recently treated with endovenous laser and foam sclerotherapy. The patient was a 44-year-old male with systemic sclerosis who commenced minocycline for the treatment of rosacea 5 months prior. Histological examination of the discolored tissue and underlying vein revealed hemosiderin deposition in the dermis and pigmented macrophages within the sub-endothelial layer of the vein wall with a staining pattern consistent with MIP. Venous tissue has not previously been reported in the literature as a target of minocycline pigmentation. Our patient preferred to control his rosacea by continuing to take minocycline. Follow-up ultrasound examinations revealed the treated vessels to be fully occluded with no evidence of recanalization, residual flow or ongoing thrombophlebitis. Despite a good sclerotherapy outcome, the pigmentation did not subside over 2 years. This case demonstrates that oral minocycline may induce significant and potentially long-term pigmentation in predisposed patients undergoing sclerotherapy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Minocycline attenuates streptomycin-induced cochlear hair cell death by inhibiting protein nitration and poly (ADP-ribose) polymerase activation.

PubMed

Wang, Ping; Li, Haonan; Yu, Shuyuan; Jin, Peng; Hassan, Abdurahman; Du, Bo

2017-08-24

This study aimed to elucidate the protective effect of minocycline against streptomycin-induced damage of cochlear hair cells and its mechanism. Cochlear membranes were isolated from newborn Wistar rats and randomly divided into control, 500μmol/L streptomycin, 100μmol/L minocycline, and streptomycin and minocycline treatment groups. Hair cell survival was analyzed by detecting the expression of 3-nitrotyrosine (3-NT) in cochlear hair cells by immunofluorescence and an enzyme-linked immunosorbent assay. Expression of 3-NT and inducible nitric oxide synthase (iNOS), and poly (ADP-Ribose) polymerase (PARP) and caspase-3 activation were evaluated by western blotting. The results demonstrated hair cell loss at 24h after streptomycin treatment. No change was found in supporting cells of the cochleae. Minocycline pretreatment improved hair cell survival and significantly reduced the expression of iNOS and 3-NT in cochlear tissues compared with the streptomycin treatment group. PARP and caspase-3 activation was increased in the streptomycin treatment group compared with the control group, and pretreatment with minocycline decreased cleaved PARP and activated caspase-3 expression. Minocycline protected cochlear hair cells from injury caused by streptomycin in vitro. The mechanism underlying the protective effect may be associated with the inhibition of excessive formation of nitric oxide, reduction of the nitration stress reaction, and inhibition of PARP and caspase-3 activation in cochlear hair cells. Combined minocycline therapy can be applied to patients requiring streptomycin treatment. Copyright © 2017. Published by Elsevier B.V.

A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome.

PubMed

Leigh, Mary Jacena S; Nguyen, Danh V; Mu, Yi; Winarni, Tri I; Schneider, Andrea; Chechi, Tasleem; Polussa, Jonathan; Doucet, Paul; Tassone, Flora; Rivera, Susan M; Hessl, David; Hagerman, Randi J

2013-04-01

Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Previous open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, aged 3.5 years to 16 years (n = 55, mean age 9.2 [SD, 3.6] years). Participants were randomized to minocycline or placebo for 3 months and then switched to the other treatment. Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared with placebo (2.49 ± 0.13 and 2.97 ± 0.13, respectively, p = .0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analog Scale (minocycline: 5.26 cm ± 0.46 cm, placebo: 4.05 cm ± 0.46 cm; p = .0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding, and preliminary efficacy analysis results known to investigators. Minocycline treatment for 3 months in children with FXS resulted in greater global improvement than placebo. Treatment for 3 months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline.

Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.

PubMed

Russmann, Vera; Goc, Joanna; Boes, Katharina; Ongerth, Tanja; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

2016-01-15

The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage.

PubMed

Li, Jianru; Chen, Jingsen; Mo, Hangbo; Chen, Jingyin; Qian, Cong; Yan, Feng; Gu, Chi; Hu, Qiang; Wang, Lin; Chen, Gao

2016-05-01

Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague-Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline's anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH.

Oral Minocycline for the Treatment of Diabetic Macular Edema (DME): Results of a Phase I/II Clinical Study

PubMed Central

Cukras, Catherine A.; Petrou, Philip; Chew, Emily Y.; Meyerle, Catherine B.; Wong, Wai T.

2012-01-01

Purpose. Inflammation contributes significantly to the pathogenesis of diabetic macular edema (DME). In particular, retinal microglia demonstrate increased activation and aggregation in areas of DME. Study authors investigated the safety and potential efficacy of oral minocycline, a drug capable of inhibiting microglial activation, in the treatment of DME. Methods. A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with fovea-involving DME who received oral minocycline 100 mg twice daily for 6 months. Main outcome measurements included best-corrected visual acuity (BCVA), central retinal subfield thickness (CST), and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiography (FA). Results. Findings indicated that the study drug was well tolerated and not associated with significant safety issues. In study eyes, mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0, +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on OCT decreased by −2.9%, −5.7%, −13.9, and −8.1% for the same time points. At month 6, mean area of late leakage on FA decreased by −34.4% in study eyes. Mean changes in contralateral fellow eyes also demonstrated similar trends. Improvements in outcome measures were not correlated with concurrent changes in systemic factors. Conclusions. In this pilot proof-of-concept study of DME, minocycline as primary treatment was associated with improved visual function, central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. Microglial inhibition with oral minocycline may be a promising therapeutic strategy targeting the inflammatory etiology of DME. (ClinicalTrials.gov number, NCT01120899.) PMID:22589436

Minocycline causes widespread cell death and increases microglial labeling in the neonatal mouse brain.

PubMed

Strahan, J Alex; Walker, William H; Montgomery, Taylor R; Forger, Nancy G

2017-06-01

Minocycline, an antibiotic of the tetracycline family, inhibits microglia in many paradigms and is among the most commonly used tools for examining the role of microglia in physiological processes. Microglia may play an active role in triggering developmental neuronal cell death, although findings have been contradictory. To determine whether microglia influence developmental cell death, we treated perinatal mice with minocycline (45 mg/kg) and quantified effects on dying cells and microglial labeling using immunohistochemistry for activated caspase-3 (AC3) and ionized calcium-binding adapter molecule 1 (Iba1), respectively. Contrary to our expectations, minocycline treatment from embryonic day 18 to postnatal day (P)1 caused a > tenfold increase in cell death 8 h after the last injection in all brain regions examined, including the primary sensory cortex, septum, hippocampus and hypothalamus. Iba1 labeling was also increased in most regions. Similar effects, although of smaller magnitude, were seen when treatment was delayed to P3-P5. Minocycline treatment from P3 to P5 also decreased overall cell number in the septum at weaning, suggesting lasting effects of the neonatal exposure. When administered at lower doses (4.5 or 22.5 mg/kg), or at the same dose 1 week later (P10-P12), minocycline no longer increased microglial markers or cell death. Taken together, the most commonly used microglial "inhibitor" increases cell death and Iba1 labeling in the neonatal mouse brain. Minocycline is used clinically in infant and pediatric populations; caution is warrented when using minocycline in developing animals, or extrapolating the effects of this drug across ages. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 753-766, 2017. © 2016 Wiley Periodicals, Inc.

Effect of feeding on the pharmacokinetics of oral minocycline in healthy research dogs.

PubMed

Hnot, Melanie L; Cole, Lynette K; Lorch, Gwendolen; Rajala-Schultz, Paivi J; Papich, Mark G

2015-12-01

The effect of food on minocycline oral absorption in dogs is unknown. The objective was to determine the pharmacokinetics of minocycline after administration of a single oral dose in fed and fasted dogs. Ten research hounds were administered oral minocycline (approximately 5 mg/kg) with and without food, in a crossover study, with a one-week wash-out between treatments. Blood samples were collected immediately prior to minocycline administration and over 24 h. Minocycline plasma drug concentrations were measured using high-performance liquid chromatography using ultraviolet detection and were analysed with compartmental modelling to determine primary pharmacokinetic parameters. Each dog was analysed independently, followed by calculation of means and variation of the dogs. The Wilcoxon signed-rank test [analysing secondary pharmacokinetic parameters - peak concentration (CMAX ), area under the concentration versus time curve (AUC)] was used to compare the two groups. A population pharmacokinetic modelling approach was performed using nonlinear mixed effects modelling of primary parameters for the population as fixed effects and the difference between subjects as a random effect. Covariate analysis was used to identify the source of variability in the population. No significant difference was found between treatments for AUC (P = 0.0645), although AUC was higher in fasted dogs. A significant difference was found for CMAX (P = 0.0059), with fasted dogs attaining a higher CMAX . The covariate of fed versus fasted accounted for a significant variation in the pharmacokinetics. Because feeding was a significant source of variation for the population's primary pharmacokinetic parameters and fasted dogs had higher minocycline concentrations, we recommend administering minocycline without food. © 2015 ESVD and ACVD.

A Randomized Double-Blind, Placebo-Controlled Trial of Minocycline in Children and Adolescents with Fragile X Syndrome

PubMed Central

Leigh, Mary Jacena S.; Nguyen, Danh V.; Mu, Yi; Winarni, Tri I.; Schneider, Andrea; Chechi, Tasleem; Polussa, Jonathan; Doucet, Paul; Tassone, Flora; Rivera, Susan M.; Hessl, David; Hagerman, Randi J.

2013-01-01

Objective Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Prior open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Method Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, ages 3.5-16 years (n=55, mean age 9.2 (SD 3.6 years)). Participants were randomized to minocycline or placebo for three months, then switched to the other treatment. Results Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared to placebo (2.49 ±0.13, 2.97 ±0.13, respectively, p 0.0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analoge Scale (minocycline 5.26 cm ±0.46 cm, placebo 4.05 cm±0.46cm; p 0.0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding and preliminary efficacy analysis results known to investigators. Conclusion Minocycline treatment for three months in children with FXS resulted in greater global improvement than placebo. Treatment for three months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline. PMID:23572165

Minocycline prevents cerebral malaria, confers neuroprotection and increases survivability of mice during Plasmodium berghei ANKA infection.

PubMed

Apoorv, Thittayil Suresh; Babu, Phanithi Prakash

2017-02-01

Cerebral malaria (CM) is a neurological complication arising due to Plasmodium falciparum or Plasmodium vivax infection. Minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. In this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ECM). The currently accepted mouse model, C57BL/6 mice infected with Plasmodium berghei ANKA, was used for the study. Infected mice were treated with an intra-peritoneal dose of minocycline hydrochloride, 45mg/kg daily for ten days that led to parasite clearance in blood, brain, liver and spleen on 7th day post-infection; and the mice survived until experiment ended (90days) without parasite recrudescence. Evans blue extravasation assay showed that blood-brain barrier integrity was maintained by minocycline. The tumor necrosis factor-alpha protein level and caspase activity, which is related to CM pathogenesis, was significantly reduced in the minocycline-treated group. Fluoro-Jade® C and hematoxylin-eosin staining of the brains of minocycline group revealed a decrease in degenerating neurons and absence of hemorrhages respectively. Minocycline treatment led to decrease in gene expressions of inflammatory mediators like interferon-gamma, CXCL10, CCL5, CCL2; receptors CXCR3 and CCR2; and hence decrease in T-cell-mediated cerebral inflammation. We also proved that this reduction in gene expressions is irrespective of the anti-parasitic property of minocycline. The distinct ability of minocycline to modulate gene expressions of CXCL10 and CXCR3 makes it effective than doxycycline, a tetracycline used as chemoprophylaxis. Our study shows that minocycline is highly effective in conferring neuroprotection during ECM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure

PubMed Central

Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; Gelfand, Robert; Mahata, Sushil K.

2015-01-01

This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15–21 (E15–E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocycline. Pups were killed on postnatal day 15 (P15). Additional pregnant dams received twice daily IP injections of cocaine (from E15–E21) + oral administration of a relatively higher (37.5 mg/kg BW) dose of minocycline. Minocycline treatment continued from E15 until the pups were sacrificed on P15. In utero cocaine exposure resulted in an increase in oxidative stress and fetal cardiac myocyte apoptosis through activation of c-Jun-NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK)-mediated mitochondria-dependent apoptotic pathway. Continued minocycline treatment from E15 through P15 significantly prevented oxidative stress, kinase activation, perturbation of BAX/BCL-2 ratio, cytochrome c release, caspase activation, and attenuated fetal cardiac myocyte apoptosis after prenatal cocaine exposure. These results demonstrate in vivo cardioprotective effects of minocycline in preventing fetal cardiac myocyte death after prenatal cocaine exposure. Given its proven clinical safety and ability to cross the placental barrier and enter into the fetal circulation, minocycline may be an effective therapy for preventing cardiac consequences of in utero cocaine exposure. PMID:21424555

Chronic minocycline treatment improves social recognition memory in adult male Fmr1 knockout mice.

PubMed

Yau, Suk Yu; Chiu, Christine; Vetrici, Mariana; Christie, Brian R

2016-10-01

Fragile X syndrome (FXS) is caused by a mutation in the Fmr1 gene that leads to silencing of the gene and a loss of its gene product, Fragile X mental retardation protein (FMRP). Some of the key behavioral phenotypes for FXS include abnormal social anxiety and sociability. Here we show that Fmr1 knock-out (KO) mice exhibit impaired social recognition when presented with a novel mouse, and they display normal social interactions in other sociability tests. Administering minocycline to Fmr1 KO mice throughout critical stages of neural development improved social recognition memory in the novel mouse recognition task. To determine if synaptic changes in the prefrontal cortex (PFC) could have played a role in this improvement, we examined PSD-95, a member of the membrane-associated guanylate kinase family, and signaling molecules (ERK1/2, and Akt) linked to synaptic plasticity in the PFC. Our analyses indicated that while minocycline treatment can enhance behavioral performance, it does not enhance expression of PSD-95, ERK1/2 or Akt in the PFC. Copyright © 2016 Elsevier B.V. All rights reserved.

Effective combination of human bone marrow mesenchymal stem cells and minocycline in experimental autoimmune encephalomyelitis mice

PubMed Central

2013-01-01

Introduction Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of the central nervous system (CNS). Minocycline ameliorates the clinical severity of MS and exhibits antiinflammatory, neuroprotective activities, and good tolerance for long-term use, whereas it is toxic to the CNS. Recently, the immunomodulation and neuroprotection capabilities of human bone marrow mesenchymal stem cells (hBM-MSCs) were shown in experimental autoimmune encephalomyelitis (EAE). In this study, we evaluated whether the combination of hBM-MSCs and a low-dose minocycline could produce beneficial effects in EAE mice. Methods The sensitivity of hBM-MSCs to minocycline was determined by an established cell-viability assay. Minocycline-treated hBM-MSCs were also characterized with flow cytometry by using MSC surface markers and analyzed for their multiple differentiation capacities. EAE was induced in C57BL/6 mice by using immunization with MOG35-55. Immunopathology assays were used to detect the inflammatory cells, demyelination, and neuroprotection. Interferon gamma (IFN-γ)/tumor necrosis factor alpha (TNF-α) and interleukin-4 (IL-4)/interleukin-10 (IL-10), the hallmark cytokines that direct Th1 and Th2 development, were detected with enzyme-linked immunosorbent assay (ELISA). terminal dUTP nick-end labeling (TUNEL) staining was performed to elucidate the cell apoptosis in the spinal cords of EAE mice. Results Minocycline did not affect the viability, surface phenotypes, or differentiation capacity of hBM-MSCs, while minocycline affected the viability of astrocytes at a high dose. In vivo efficacy experiments showed that combined treatment, compared to the use of minocycline or hBM-MSCs alone, resulted in a significant reduction in clinical scores, along with attenuation of inflammation, demyelination, and neurodegeneration. Moreover, the combined treatment with hBM-MSCs and minocycline enhanced the immunomodulatory effects, which suppressed proinflammatory

Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration

PubMed Central

Cheng, Shanshan; Hou, Jinxing; Zhang, Chen; Xu, Congyu; Wang, Long; Zou, Xiaoxia; Yu, Huahong; Shi, Yun; Yin, Zhenyu; Chen, Guiquan

2015-01-01

Minocycline is a broad-spectrum tetracycline antibiotic. A number of preclinical studies have shown that minocycline exhibits neuroprotective effects in various animal models of neurological diseases. However, it remained unknown whether minocycline is effective to prevent neuron loss. To systematically evaluate its effects, minocycline was used to treat Dicer conditional knockout (cKO) mice which display age-related neuron loss. The drug was given to mutant mice prior to the occurrence of neuroinflammation and neurodegeneration, and the treatment had lasted 2 months. Levels of inflammation markers, including glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule1 (Iba1) and interleukin6 (IL6), were significantly reduced in minocycline-treated Dicer cKO mice. In contrast, levels of neuronal markers and the total number of apoptotic cells in Dicer cKO mice were not affected by the drug. In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis. PMID:26000566

Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

PubMed Central

Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

2014-01-01

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

A systematic review on potential mechanisms of minocycline in kidney diseases.

PubMed

Haghi-Aminjan, Hamed; Asghari, Mohammad Hossein; Goharbari, Mohammad Hadi; Abdollahi, Mohammad

2017-08-01

Kidney diseases need specialized health care and still are a reason of death. There is a large body of evidence that indicates minocycline possesses some cytoprotective effects beside of antibacterial properties. In this review, we aimed to explain cytoprotective mechanisms and kidney protection of minocycline. In order to find the effects of minocycline on kidney diseases a systematic literature search was performed, according to the guidelines proposed at the PRISMA statement in the electronic databases, including: PubMed, Scopus, and Web of Science up to August 2016, using the term 'minocycline' combined either by 'kidney' or 'renal' and published in English language. The following criteria were included: (1) studies that used minocycline in renal diseases; (2) full-text articles; (3) English language; (4) no limitation in publications with in-vivo or in-vitro and human or animal subjects. Our search provided a total of 1056 articles which 1045 of them were discarded due to not meeting the inclusion criteria. It has been clear that several factors, including apoptosis, oxidative stress, mitochondrial dysfunction and inflammation have pivotal roles in the development and progression of kidney diseases. Minocycline protective properties are via several ways, including anti-apoptotic, free radical scavenging, anti-inflammatory, effect on mitochondrial functions and inhibition of matrix metalloproteinase. This systematic review confirmed that minocycline could have significant effects on treatment of renal malfunctions. However, regarding any possible adverse effects of antibiotics, it appears that more investigation is still needed in this context. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

COMMUNICATION: Minocycline increases quality and longevity of chronic neural recordings

NASA Astrophysics Data System (ADS)

Rennaker, R. L.; Miller, J.; Tang, H.; Wilson, D. A.

2007-06-01

Brain/machine interfaces could potentially be used in the treatment of a host of neurological disorders ranging from paralysis to sensory deficits. Insertion of chronic micro-electrode arrays into neural tissue initiates a host of immunological responses, which typically leads to the formation of a cellular sheath around the implant, resulting in the loss of useful signals. Minocycline has been shown to have neuroprotective and neurorestorative effects in certain neural injury and neurodegenerative disease models. This study examined the effects of minocycline administration on the quality and longevity of chronic multi-channel microwire neural implants 1 week and 1 month post-implantation in auditory cortex. The mean signal-to-noise ratio for the minocycline group stabilized at the end of week 1 and remained above 4.6 throughout the following 3 weeks. The control group signal-to-noise ratio dropped throughout the duration of the study and at the end of 4 weeks was 2.6. Furthermore, 68% of electrodes from the minocycline group showed significant stimulus-driven activity at week 4 compared to 12.5% of electrodes in the control group. There was a significant reduction in the number of activated astrocytes around the implant in minocycline subjects, as well as a reduction in total area occupied by activated astrocytes at 1 and 4 weeks.

Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure.

PubMed

Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; Gelfand, Robert; Mahata, Sushil K; Sinha-Hikim, Amiya P

2011-06-01

This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15-21 (E15-E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocycline. Pups were killed on postnatal day 15 (P15). Additional pregnant dams received twice daily IP injections of cocaine (from E15-E21) + oral administration of a relatively higher (37.5 mg/kg BW) dose of minocycline. Minocycline treatment continued from E15 until the pups were sacrificed on P15. In utero cocaine exposure resulted in an increase in oxidative stress and fetal cardiac myocyte apoptosis through activation of c-Jun-NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK)-mediated mitochondria-dependent apoptotic pathway. Continued minocycline treatment from E15 through P15 significantly prevented oxidative stress, kinase activation, perturbation of BAX/BCL-2 ratio, cytochrome c release, caspase activation, and attenuated fetal cardiac myocyte apoptosis after prenatal cocaine exposure. These results demonstrate in vivo cardioprotective effects of minocycline in preventing fetal cardiac myocyte death after prenatal cocaine exposure. Given its proven clinical safety and ability to cross the placental barrier and enter into the fetal circulation, minocycline may be an effective therapy for preventing cardiac consequences of in utero cocaine exposure.

Minocycline, but not ascorbic acid, increases motor activity and extends the life span of Drosophila melanogaster.

PubMed

Mora, Marylhi; Medina-Leendertz, Shirley J; Bonilla, Ernesto; Terán, Raikelin E; Paz, Milagros C; Arcaya, José Luis

2013-06-01

In the present study we compared the effects of minocycline and ascorbic acid in the life span, motor activity and lipid peroxidation of Drosophila melanogaster, in an effort to find a substance capable of providing protection against oxidative stress in aging. In the flies treated with minocycline a very significant increase in the life span (101 +/- 1.33 days) was observed when compared to those treated with ascorbic acid and controls (42.3% and 38.4%, respectively). The motor activity of minocycline treated flies also increased significantly with respect to control and ascorbic acid fed flies, from the 3rd to the 9th week of treatment. With regard to lipid peroxidation, it was found that the levels of malondialdehyde (MDA) in flies treated with minocycline showed no statistical differences to the control on the first day of treatment, but a significantly lower content on the day of 50% survival. In contrast, in flies treated with ascorbic acid significantly elevated levels of MDA compared to control and minocycline treated flies were detected throughout. These results suggest a protective effect of minocycline against oxidative stress and aging in D. melanogaster. An inhibitory effect on reactive oxygen species production may be an important contributing factor.

Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice.

PubMed

Vogt, M A; Mallien, A S; Pfeiffer, N; Inta, I; Gass, P; Inta, D

2016-03-15

Minocycline is a broad-spectrum tetracycline antibiotic with multiple actions, including anti-inflammatory and neuroprotective effects, that was proposed as novel treatment for several psychiatric disorders including schizophrenia and depression. However, there are contradictory results regarding antidepressant effects of minocycline in rodent models. Additionally, the possible anxiolytic effect of minocycline is still poorly investigated. Therefore, we aimed to clarify in the present study the influence of minocycline on behavioral correlates of mood disorders in standard tests for depression and anxiety, the Porsolt Forced Swim Test (FST), Elevated O-Maze, Dark-Light Box Test and Openfield Test in adult C57BL/6 mice. We found, unexpectedly, that mice treated with minocycline (20-40mg/kg, i.p.) did not display antidepressant- or anxiolytic-like behavioral changes in contrast to mice treated with diazepam (0.5mg/kg, anxiety tests) or imipramine (20mg/kg, depressive-like behavior). These results are relevant for future studies, considering that C57BL/6 mice, the most widely used strain in pharmacological and genetic animal models, did not react as expected to the treatment regime applied. Copyright © 2015 Elsevier B.V. All rights reserved.

Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain.

PubMed

Inta, Ioana; Vogt, Miriam A; Vogel, Anne S; Bettendorf, Markus; Gass, Peter; Inta, Dragos

2016-10-01

NMDA receptor (NMDAR) antagonists induce in perinatal rodent cortical apoptosis and protracted schizophrenia-like alterations ameliorated by antipsychotic treatment. The broad-spectrum antibiotic minocycline elicits antipsychotic and neuroprotective effects. Here we tested, if minocycline protects also against apoptosis triggered by the NMDAR antagonist MK-801 at postnatal day 7. Surprisingly, minocycline induced widespread cortical apoptosis and exacerbated MK-801-triggered cell death. In some areas such as the subiculum, the pro-apoptotic effect of minocycline was even more pronounced than that elicited by MK-801. These data reveal among antipsychotics unique pro-apoptotic properties of minocycline, raising concerns regarding consequences for brain development and the use in children.

Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase

PubMed Central

Siller, Saul S.; Broadie, Kendal

2011-01-01

SUMMARY Fragile X syndrome (FXS), caused by loss of the fragile X mental retardation 1 (FMR1) product (FMRP), is the most common cause of inherited intellectual disability and autism spectrum disorders. FXS patients suffer multiple behavioral symptoms, including hyperactivity, disrupted circadian cycles, and learning and memory deficits. Recently, a study in the mouse FXS model showed that the tetracycline derivative minocycline effectively remediates the disease state via a proposed matrix metalloproteinase (MMP) inhibition mechanism. Here, we use the well-characterized Drosophila FXS model to assess the effects of minocycline treatment on multiple neural circuit morphological defects and to investigate the MMP hypothesis. We first treat Drosophila Fmr1 (dfmr1) null animals with minocycline to assay the effects on mutant synaptic architecture in three disparate locations: the neuromuscular junction (NMJ), clock neurons in the circadian activity circuit and Kenyon cells in the mushroom body learning and memory center. We find that minocycline effectively restores normal synaptic structure in all three circuits, promising therapeutic potential for FXS treatment. We next tested the MMP hypothesis by assaying the effects of overexpressing the sole Drosophila tissue inhibitor of MMP (TIMP) in dfmr1 null mutants. We find that TIMP overexpression effectively prevents defects in the NMJ synaptic architecture in dfmr1 mutants. Moreover, co-removal of dfmr1 similarly rescues TIMP overexpression phenotypes, including cellular tracheal defects and lethality. To further test the MMP hypothesis, we generated dfmr1;mmp1 double null mutants. Null mmp1 mutants are 100% lethal and display cellular tracheal defects, but co-removal of dfmr1 allows adult viability and prevents tracheal defects. Conversely, co-removal of mmp1 ameliorates the NMJ synaptic architecture defects in dfmr1 null mutants, despite the lack of detectable difference in MMP1 expression or gelatinase activity

[Minocycline as a therapeutic drug for methamphetamine use disorders].

PubMed

Hashimoto, Kenji

2008-02-01

Use of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) is an extremely serious and growing problem throughout the world, including Japan. Antipsychotic drugs have been used for psychotic symptoms associated with these abused drugs. However, there are currently no particular pharmacological treatments for the wide range of symptoms associated with these abused drugs. Recently, we reported that the second generation antibiotic drug minocycline can attenuate behavioral abnormalities and neurotoxicity in the brain after administration of methamphetamine or MDMA. In this review, we discuss minocycline as a new potential therapeutic drug for schizophrenia as well as psychosis associated with these abused drugs.

Pulmonary disposition and pharmacokinetics of minocycline in adult horses.

PubMed

Echeverria, Kate O; Lascola, Kara M; Giguère, Steeve; Foreman, Jonathan H; Austin, Scott A

2017-11-01

OBJECTIVE To determine pharmacokinetics and pulmonary disposition of minocycline in horses after IV and intragastric administration. ANIMALS 7 healthy adult horses. PROCEDURES For experiment 1 of the study, minocycline was administered IV (2.2 mg/kg) or intragastrically (4 mg/kg) to 6 horses by use of a randomized crossover design. Plasma samples were obtained before and 16 times within 36 hours after minocycline administration. Bronchoalveolar lavage (BAL) was performed 4 times within 24 hours after minocycline administration for collection of pulmonary epithelial lining fluid (PELF) and BAL cells. For experiment 2, minocycline was administered intragastrically (4 mg/kg, q 12 h, for 5 doses) to 6 horses. Plasma samples were obtained before and 20 times within 96 hours after minocycline administration. A BAL was performed 6 times within 72 hours after minocycline administration for collection of PELF samples and BAL cells. RESULTS Mean bioavailability of minocycline was 48% (range, 35% to 75%). At steady state, mean ± SD maximum concentration (Cmax) of minocycline in plasma was 2.3 ± 1.3 μg/mL, and terminal half-life was 11.8 ± 0.5 hours. Median time to Cmax (Tmax) was 1.3 hours (interquartile range [IQR], 1.0 to 1.5 hours). The Cmax and Tmax of minocycline in the PELF were 10.5 ± 12.8 μg/mL and 9.0 hours (IQR, 5.5 to 12.0 hours), respectively. The Cmax and Tmax for BAL cells were 0.24 ± 0.1 μg/mL and 6.0 hours (IQR, 0 to 6.0 hours), respectively. CONCLUSIONS AND CLINICAL RELEVANCE Minocycline was distributed into the PELF and BAL cells of adult horses.

Comparison of Minocycline Susceptibility Testing Methods for Carbapenem-Resistant Acinetobacter baumannii.

PubMed

Wang, Peng; Bowler, Sarah L; Kantz, Serena F; Mettus, Roberta T; Guo, Yan; McElheny, Christi L; Doi, Yohei

2016-12-01

Treatment options for infections due to carbapenem-resistant Acinetobacter baumannii are extremely limited. Minocycline is a semisynthetic tetracycline derivative with activity against this pathogen. This study compared susceptibility testing methods that are used in clinical microbiology laboratories (Etest, disk diffusion, and Sensititre broth microdilution methods) for testing of minocycline, tigecycline, and doxycycline against 107 carbapenem-resistant A. baumannii clinical isolates. Susceptibility rates determined with the standard broth microdilution method using cation-adjusted Mueller-Hinton (MH) broth were 77.6% for minocycline and 29% for doxycycline, and 92.5% of isolates had tigecycline MICs of ≤2 μg/ml. Using MH agar from BD and Oxoid, susceptibility rates determined with the Etest method were 67.3% and 52.3% for minocycline, 21.5% and 18.7% for doxycycline, and 71% and 29.9% for tigecycline, respectively. With the disk diffusion method using MH agar from BD and Oxoid, susceptibility rates were 82.2% and 72.9% for minocycline and 34.6% and 34.6% for doxycycline, respectively, and rates of MICs of ≤2 μg/ml were 46.7% and 23.4% for tigecycline. In comparison with the standard broth microdilution results, very major rates were low (∼2.8%) for all three drugs across the methods, but major error rates were higher (∼5.6%), especially with the Etest method. For minocycline, minor error rates ranged from 14% to 37.4%. For tigecycline, minor error rates ranged from 6.5% to 69.2%. The majority of minor errors were due to susceptible results being reported as intermediate. For minocycline susceptibility testing of carbapenem-resistant A. baumannii strains, very major errors are rare, but major and minor errors overcalling strains as intermediate or resistant occur frequently with susceptibility testing methods that are feasible in clinical laboratories. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice.

PubMed

Hou, Yue; Xie, Guanbo; Liu, Xia; Li, Guoxun; Jia, Congcong; Xu, Jinghua; Wang, Bing

2016-03-01

The role of glial cells, especially microglia and astrocytes, in neuroinflammation and cognition has been studied intensively. Lipopolysaccharide (LPS), a commonly used inducer of neuroinflammation, can cause cognitive impairment. Minocycline is known to possess potent neuroprotective activity, but its effect on LPS-induced cognitive impairment is unknown. This study aims to investigate the effects of minocycline on LPS-induced cognitive impairment and glial cell activation in mice. Behavioral tests were conducted for cognitive function, immunohistochemistry for microglial and astrocyte response, and quantitative PCR for mRNA expression of proinflammatory cytokines. Minocycline significantly reversed the decreased spontaneous alternation induced by intrahippocampal administration of LPS in the Y-maze task. In the Morris water maze place navigation test, minocycline decreased the escape latency and distance traveled compared to LPS-treated mice. In the probe test, minocycline-treated mice spent more time in the target quadrant and crossed the platform area more frequently than animals in the LPS-treated group. Minocycline produced a significant decrease in the number of Iba-1- and GFAP-positive hippocampal cells compared to the LPS-treated group. Minocycline-treated mice had significantly reduced hippocampal TNF-α and IL-1β mRNA levels compared with LPS-treated animals. Minocycline caused a significant increase in hippocampal BDNF expression compared to the LPS-treated group. Minocycline can attenuate LPS-induced cognitive impairments in mice. This effect may be associated with its action to suppress the activation of microglia and astrocytes and to normalize BDNF expression. Since neuroinflammatory processes and cognitive impairments are implicated in neurodegenerative disorders, minocycline may be a promising candidate for treating such diseases.

Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex.

PubMed

Li, Shih-Wen; Chen, Yu-Chieh; Sheen, Jiunn-Ming; Hsu, Mei-Hsin; Tain, You-Lin; Chang, Kow-Aung; Huang, Li-Tung

2017-07-01

Bile duct ligation (BDL) model is used to study hepatic encephalopathy accompanied by cognitive impairment. We employed the proteomic analysis approach to evaluate cognition-related proteins in the prefrontal cortex of young BDL rats and analyzed the effect of minocycline on these proteins and spatial memory. BDL was induced in young rats at postnatal day 17. Minocycline as a slow-release pellet was implanted into the peritoneum. Morris water maze test and two-dimensional liquid chromatography-tandem mass spectrometry were used to evaluate spatial memory and prefrontal cortex protein expression, respectively. We used 2D/LC-MS/MS to analyze for affected proteins in the prefrontal cortex of young BDL rats. Results were verified with Western blotting, immunohistochemistry, and quantitative real-time PCR. The effect of minocycline in BDL rats was assessed. BDL induced spatial deficits, while minocycline rescued it. Collapsin response mediator protein 2 (CRMP2) and manganese-dependent superoxide dismutase (MnSOD) were upregulated and nucleoside diphosphate kinase B (NME2) was downregulated in young BDL rats. BDL rats exhibited decreased levels of brain-derived neurotrophic factor (BDNF) mRNA as compared with those by the control. However, minocycline treatment restored CRMP2 and NME2 protein expression, BDNF mRNA level, and MnSOD activity to control levels. We demonstrated that BDL altered the expression of CRMP2, NME2, MnSOD, and BDNF in the prefrontal cortex of young BDL rats. However, minocycline treatment restored the expression of the affected mediators that are implicated in cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of retinoic acid catabolism by minocycline: evidence for a novel mode of action?

PubMed

Regen, Francesca; Hildebrand, Martin; Le Bret, Nathalie; Herzog, Irmelin; Heuser, Isabella; Hellmann-Regen, Julian

2015-06-01

Retinoic acid (RA) represents an essential and highly potent endogenous retinoid with pronounced anti-inflammatory properties and potent anti-acne activity, and has recently been suggested to share a common anti-inflammatory mode of action with tetracycline antibiotics. We hypothesized that tetracyclines may directly interfere with RA homeostasis via inhibition of its local cytochrome P450 (CYP450)-mediated degradation, an essential component of tightly regulated skin RA homeostasis. To test this hypothesis, we performed controlled in vitro RA metabolism assays using rat skin microsomes and measured RA levels in a RA-synthesizing human keratinocyte cell line, both in the presence and in the absence of minocycline, a tetracycline popular in acne treatment. Interestingly, minocycline potently blocked RA degradation in rat skin microsomes, and strikingly enhanced RA levels in RA-synthesizing cell cultures, in a dose-dependent manner. These findings indicate a potential role for CYP-450-mediated RA metabolism in minocycline's pleiotropic mode of action and anti-acne efficacy and could account for the overlap between minocycline and RA-induced effects at the level of their molecular mode of action, but also clinically at the level of the rare side effect of pseudotumor cerebri, which is observed for both, RA and minocycline treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

New thermoresistant polymorph from CO2 recrystallization of minocycline hydrochloride.

PubMed

Rodrigues, Miguel A; Tiago, João M; Padrela, Luis; Matos, Henrique A; Nunes, Teresa G; Pinheiro, Lídia; Almeida, António J; de Azevedo, Edmundo Gomes

2014-11-01

To prepare and thoroughly characterize a new polymorph of the broad-spectrum antibiotic minocycline from its hydrochloride dehydrate salts. The new minocycline hydrochloride polymorph was prepared by means of the antisolvent effect caused by carbon dioxide. Minocycline recrystallized as a red crystalline hydrochloride salt, starting from solutions or suspensions containing CO2 and ethanol under defined conditions of temperature, pressure and composition. This novel polymorph (β-minocycline) revealed characteristic PXRD and FTIR patterns and a high melting point (of 247 ºC) compared to the initial minocycline hydrochloride hydrates (α-minocycline). Upon dissolution the new polymorph showed full anti-microbial activity. Solid-state NMR and DSC studies evidenced the higher chemical stability and crystalline homogeneity of β-minocycline compared to the commercial chlorohydrate powders. Molecular structures of both minocyclines present relevant differences as shown by multinuclear solid-state NMR. This work describes a new crystalline structure of minocycline and evidences the ability of ethanol-CO2 system in removing water molecules from the crystalline structure of this API, at modest pressure, temperature and relatively short time (2 h), while controlling the crystal habit. This process has therefore the potential to become a consistent alternative towards the control of the solid form of APIs.

Modified protocol including topical minocycline in orabase to manage medication-related osteonecrosis of the jaw cases.

PubMed

Karasneh, Jumana A; Al-Eryani, Kamal; Clark, Glenn T; Sedghizadeh, Parish P

2016-10-01

Management of medication-related osteone-crosis of the jaw (MRONJ) with active infection can be a serious challenge for clinicians. Based on Association of Oral and Maxillofacial Surgeons (AAOMS) recommendations, we have tested a modified treatment protocol using topical minocycline. Five patients diagnosed with stage II or III MRONJ lesions were willing to consent to our protocol. In addition to conventional treatment as suggested by the AAOMS, such as, surgical debridement, chlorhexidine irrigation, and systemic antibiotics, we applied 10% minocycline to the lesions once a week for sustained local antibiotic delivery. All five patients reported pain relief after the first minocycline application. Complete healing occurred in three patients; case three healed completely after the third application, one case continues to improve toward resolution and one withdraws due to other non-relevant medical problem. In this study, we are reporting favorable results using a modified protocol with topical minocycline to treat MRONJ lesions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Successful Prophylactic Minocycline Treatment for Recurrent Helicobacter Cinaedi Sepsis during Chemotherapy in a Patient with Follicular Lymphoma].

PubMed

Aota, Yasuo; Gotoh, Akihiko; Nakamura, Itaru; Motoya, Kazuki; Okuda, Yuko; Hanyu, Naofumi; Honma, Toshihiro; Udou, Ryutaro; Yokoyama, Tomohisa; Kitagawa, Naoyuki; Komatsu, Norio

2017-05-01

A 63-year-old man with follicular lymphoma was administered standard R-CHOP chemotherapy. Six days after the second course of chemotherapy, the patient developed fever and chills. Blood cultures yielded rod-shaped gram-negative bacteria, but no further identification was obtained. High fever and chills returned on the fifth and sixth days after the third and fourth courses of R-CHOP, respectively. These blood cultures were also positive. Since we detected spiral-shaped gram-negative rods, we performed a prolonged culture during the febrile period after the fourth course of R-CHOP. This revealed the formation of characteristic film-like colonies, and Helicobacter cinaedi(H. cinaedi)bacteria was identified. After final identification, the patient was administered prophylactic minocycline treatment. Subsequent blood cultures were negative, fever did not recur, and we were able to complete 6 courses of R-CHOP. Although H. cinaedi has been reported to be a cause of sepsis in immunocompromised patients, standard correlation has not been established. Our case suggests that H. cinaedi should be considered when recurrent fever is observed after chemotherapy. Prophylactic antibiotic treatment with minocycline may prevent sepsis, as observed in our case.

Expression profiling of genes modulated by minocycline in a rat model of neuropathic pain

PubMed Central

2014-01-01

Background The molecular mechanisms underlying neuropathic pain are constantly being studied to create new opportunities to prevent or alleviate neuropathic pain. The aim of our study was to determine the gene expression changes induced by sciatic nerve chronic constriction injury (CCI) that are modulated by minocycline, which can effectively diminish neuropathic pain in animal studies. The genes associated with minocycline efficacy in neuropathic pain should provide insight into the etiology of neuropathic pain and identify novel therapeutic targets. Results We screened the ipsilateral dorsal part of the lumbar spinal cord of the rat CCI model for differentially expressed genes. Out of 22,500 studied transcripts, the abundance levels of 93 transcripts were altered following sciatic nerve ligation. Percentage analysis revealed that 54 transcripts were not affected by the repeated administration of minocycline (30 mg/kg, i.p.), but the levels of 39 transcripts were modulated following minocycline treatment. We then selected two gene expression patterns, B1 and B2. The first transcription pattern, B1, consisted of 10 mRNA transcripts that increased in abundance after injury, and minocycline treatment reversed or inhibited the effect of the injury; the B2 transcription pattern consisted of 7 mRNA transcripts whose abundance decreased following sciatic nerve ligation, and minocycline treatment reversed the effect of the injury. Based on the literature, we selected seven genes for further analysis: Cd40, Clec7a, Apobec3b, Slc7a7, and Fam22f from pattern B1 and Rwdd3 and Gimap5 from pattern B2. Additionally, these genes were analyzed using quantitative PCR to determine the transcriptional changes strongly related to the development of neuropathic pain; the ipsilateral DRGs (L4-L6) were also collected and analyzed in these rats using qPCR. Conclusion In this work, we confirmed gene expression alterations previously identified by microarray analysis in the spinal cord and

Cardiac Uptake of Minocycline and Mechanisms for In Vivo Cardioprotection

PubMed Central

Romero-Perez, Diego; Fricovsky, Eduardo; Yamasaki, Katrina Go; Griffin, Michael; Barraza-Hidalgo, Maraliz; Dillmann, Wolfgang; Villarreal, Francisco

2008-01-01

Objectives The ability of minocycline to be transported into cardiac cells, concentrate in normal and ischemic myocardium and act as in vivo cardioprotector was examined. We also determined minocycline's capacity to act as a reducer of myocardial oxidative stress and matrix metalloproteinase (MMP) activity. Background The identification of compounds with the potential to reduce myocardial ischemic injury is of great interest. Tetracyclines (TTCs) are antibiotics with pleiotropic cytoprotective properties that accumulate in normal and diseased tissues. Minocycline is highly lipophilic and has shown promise as a possible cardioprotector. However, minocycline's potential as an in vivo cardioprotector as well as the means by which this action is attained are not well understood. Methods Rats were subjected to 45 min of ischemia and 48 h of reperfusion. Animals were treated 48 h before and 48 h after thoracotomy with either vehicle or 50 mg/kg/day minocycline. Tissue samples were used for biochemical assays and cultured cardiac cells for minocycline uptake experiments. Results Minocycline significantly reduced infarct size (∼33%), tissue MMP-9 activity and oxidative stress. Minocycline was concentrated ∼24-fold in normal (0.5 mM) and ∼50-fold in ischemic regions (1.1 mM) vs. blood. Neonatal rat cardiac fibroblasts, myocytes and adult fibroblasts demonstrate a time- and temperature-dependent uptake of minocycline to levels that approximate those of normal myocardium. Conclusions Given the high intracellular levels observed and results from the assessment of in vitro antioxidant and MMP inhibitor capacities, it is likely that minocycline acts to limit myocardial ischemic injury via mass action effects. PMID:18848143

Does minocycline, an antibiotic with inhibitory effects on microglial activation, sharpen a sense of trust in social interaction?

PubMed

Watabe, Motoki; Kato, Takahiro A; Monji, Akira; Horikawa, Hideki; Kanba, Shigenobu

2012-04-01

Minocycline has long been applied to various infectious diseases as a tetracycline antibiotic and recently has found new application in the treatment of brain diseases such as stroke and multiple sclerosis. In addition, minocycline has also been suggested as an effective drug for psychiatric diseases. These suggestions imply that minocycline may modulate our mental activities, while the underlying mechanism remains to be clarified. To investigate how minocycline influences human mental activity, we experimentally examined how minocycline works on human social decision making in a double-blind randomized trial. Forty-nine healthy volunteers were administered minocycline or placebo over four days, after which they played (1) a trust game, in which they decided how much to trust an anonymous partner, and (2) a dictator game, in which they decided how to divide resources between themselves and an anonymous partner. The minocycline group did not display increased trusting behavior or more altruistic resource allocation. In fact, the minocycline group displayed a slight reduction in trusting behavior. However, the minocycline group did show a strong positive correlation between the degree of risk taking in the trust game and in a separate evaluation of others' trustworthiness, whereas the placebo group showed no such correlation. These results suggest that minocycline led to more rational decision-making strategies, possibly by increasing emotion regulation. Since minocycline is a well-known inhibitor of microglial activation, our findings may open a new optional pathway for treating mental states in which a component of rational decision making is impaired.

Minocycline Reduces Spontaneous Hemorrhage in Mouse Models of Cerebral Amyloid Angiopathy

PubMed Central

Liao, Fan; Xiao, Qingli; Kraft, Andrew; Gonzales, Ernie; Perez, Ron; Greenberg, Steven M.; Holtzman, David; Lee, Jin-Moo

2015-01-01

Background and Purpose Cerebral Amyloid Angiopathy (CAA) is a common cause of recurrent intracerebral hemorrhage (ICH) in the elderly. Previous studies have shown that CAA induces inflammation and expression of matrix metalloproteinase-2 and -9 (gelatinases) in amyloid-laden vessels. Here, we inhibited both using minocycline in CAA mouse models to determine if spontaneous ICH could be reduced. Methods Tg2576 (n=16) and 5×FAD/ApoE4 knock-in mice (n=16), aged to 17 and 12 months, respectively, were treated with minocycline (50 mg/kg, i.p.) or saline every other day for two months. Brains were extracted and stained with X-34 (to quantify amyloid), Perl’s blue (to quantify hemorrhage), and immunostained to examined Aβ load, gliosis (GFAP, Iba-1), and vascular markers of blood-brain-barrier integrity (ZO-1 and collagen IV). Brain extracts were used to quantify mRNA for a variety of inflammatory genes. Results Minocycline treatment significantly reduced hemorrhage frequency in the brains of Tg2576 and 5×FAD/ApoE4 mice relative to the saline-treated mice, without affecting CAA load. Gliosis (GFAP and Iba-1 immunostaining), gelatinase activity, and expression of a variety of inflammatory genes (MMP-9, Nox4, CD45, S-100b, Iba-1) were also significantly reduced. Higher levels of microvascular tight junction and basal lamina proteins were found in the brains of minocycline-treated Tg2576 mice relative to saline-treated controls. Conclusions Minocycline reduced gliosis, inflammatory gene expression, gelatinase activity, and spontaneous hemorrhage in two different mouse models of CAA, supporting the importance of MMP-related and inflammatory pathways in ICH pathogenesis. As an FDA-approved drug, minocycline might be considered for clinical trials to test efficacy in preventing CAA-related ICH. PMID:25944329

Minocycline prevents Abeta(25-35)-induced reduction of somatostatin and neprilysin content in rat temporal cortex.

PubMed

Burgos-Ramos, E; Puebla-Jiménez, L; Arilla-Ferreiro, E

2009-02-13

Tetracyclines have been demonstrated to inhibit formation of beta-amyloid (Abeta) aggregates and to disassemble preformed fibrils. Minocycline, a semi-synthetic second-generation tetracycline, can reverse Abeta-induced impairment of cognitive functions. Since somatostatin is involved in cognition and we recently showed that Abeta(25-35) lowers somatostatin expression in the rat temporal cortex, our aim here was to analyze the effects of minocycline on somatostatin immunoreactivity and mRNA levels in the temporal cortex of Abeta(25-35)-infused and healthy rats. Moreover, since brain levels of neprilysin, an Abeta-degrading enzyme, decrease with age, favoring the appearance of senile neuritic plaques, we tested whether minocyline could affect neprilysin expression. Wistar rats were thus injected with minocycline twice on the first day of treatment. On the following day, and during 14 days, Abeta(25-35) or vehicle were administered. Minocycline was injected once again on days 13 and 14. All animals were sacrificed 24 h after the last drug injection. Minocycline abrogated the Abeta(25-35)-induced decrease of somatostatin-like immunoreactive content, somatostatin mRNA levels, phosphorylated-CREB content and neprilysin levels. Minocycline alone enhanced these targets. Our findings indicate that minocycline prevents the deleterious effects of Abeta(25-35) on SRIF and neprilysin expression in the rat temporal cortex and that it has protective effects per se on these parameters.

Effects of minocycline on parameters of cardiovascular recovery after cardioplegic arrest in a rabbit Langendorff heart model.

PubMed

Salameh, Aida; Halling, Michelle; Seidel, Thomas; Dhein, Stefan

2015-12-01

Pharmacological cardiac organ protection during cardiopulmonary bypass presents an opportunity for improvement. A number of different strategies have been established to minimize ischemia/reperfusion-induced damage to the heart. Among these, cardioplegia with histidine-tryptophan-ketoglutarate solution and hypothermia are the most frequently used regimens. The antibiotic minocycline has been used in this context for neuroprotection. The aim of the current study was to evaluate whether the application of minocycline prior to cardioplegia exerts a protective effect on cardiac muscle. For this purpose, this study investigated six rabbit hearts with minocycline treatment (1 μmol/L) and six without in a Langendorff model of 90 min cold cardioplegic arrest using Custodiol followed by a 30 min recovery phase. Histological analysis of cardiac muscle revealed that markers of apoptosis, oxidative and nitrosative stress were significantly lower in the minocycline group, whereas adenosine triphosphate (ATP)- and malondialdehyde (MDA)-levels and O2-consumption were not affected by minocycline. Functionally, recovery of dP/dt (max) and dP/dt (min) was significantly faster in the minocycline group than in control. This leads to the conclusion that adding minocycline to the cardioplegic solution may improve left ventricular recovery after cardioplegic arrest involving reduced pro-apoptotic effects. © 2015 Wiley Publishing Asia Pty Ltd.

Antimicrobial action of minocycline microspheres versus 810-nm diode laser on human dental plaque microcosm biofilms.

PubMed

Song, Xiaoqing; Yaskell, Tina; Klepac-Ceraj, Vanja; Lynch, Michael C; Soukos, Nikolaos S

2014-02-01

The purpose of this study is to investigate the antimicrobial effects of minocycline hydrochloride microspheres versus infrared light at 810 nm from a diode laser on multispecies oral biofilms in vitro. These biofilms were grown from dental plaque inoculum (oral microcosms) and were obtained from six systemically healthy individuals with generalized chronic periodontitis. Multispecies biofilms were derived using supra- and subgingival plaque samples from mesio-buccal aspects of premolars and molars exhibiting probing depths in the 4- to 5-mm range and 1- to 2-mm attachment loss. Biofilms were developed anaerobically on blood agar surfaces in 96-well plates using a growth medium of prereduced, anaerobically sterilized brain-heart infusion with 2% horse serum. Minocycline HCl 1 mg microspheres were applied on biofilms on days 2 and 5 of their development. Biofilms were also exposed on days 2 and 5 of their growth to 810-nm light for 30 seconds using a power of 0.8 W in a continuous-wave mode. The susceptibility of microorganisms to minocycline or infrared light was evaluated by a colony-forming assay and DNA probe analysis at different time points. At all time points of survival assessment, minocycline was more effective (>2 log10 colony-forming unit reduction) than light treatment (P <0.002). Microbial analysis did not reveal susceptibility of certain dental plaque pathogens to light, and it was not possible after treatment with minocycline due to lack of bacterial growth. The cumulative action of minocycline microspheres on multispecies oral biofilms in vitro led to enhanced killing of microorganisms, whereas a single exposure of light at 810 nm exhibited minimal and non-selective antimicrobial effects.

Effect of a controlled release device containing minocycline microspheres on the treatment of chronic periodontitis: A comparative study

PubMed Central

Gopinath, V.; Ramakrishnan, T.; Emmadi, Pamela; Ambalavanan, N.; Mammen, Biju; Vijayalakshmi

2009-01-01

Introduction: Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes. The aim of this study was to evaluate the efficacy and safety of locally administered minocycline microspheres (Arestin™) in the treatment of chronic periodontitis. Materials and Methods: A total of 60 sites from 15 patients in the age group of 35-50 years, who had periodontal pockets measuring 5-8 mm and had been diagnosed with chronic periodontitis, were selected for the study. The selected groups were randomly assigned to either the control group (group A) or the treatment/test group (group B). Only scaling and root planing were done at the base line visit for the control sites followed by local application of Arestin™ (1 mg). Clinical parameters such as plaque index, gingival index, and gingival bleeding index were recorded at baseline, day 30, day 90, and day 180 in the selected sites of both the groups. Probing pocket depth also was recorded at baseline, day 90, and day 180 for both the groups. Results: A statistically significant reduction was observed in both groups. Group B showed better results than Group A and these differences were statistically significant. Conclusion: The results of this study clearly indicate that treatment with scaling and root planing plus minocycline microspheres (Arestin™) is more effective and safer than scaling and root planing alone in reducing the signs of chronic periodontitis. PMID:20407655

Minocycline produced antidepressant-like effects on the learned helplessness rats with alterations in levels of monoamine in the amygdala and no changes in BDNF levels in the hippocampus at baseline.

PubMed

Arakawa, Shiho; Shirayama, Yukihiko; Fujita, Yuko; Ishima, Tamaki; Horio, Mao; Muneoka, Katsumasa; Iyo, Masaomi; Hashimoto, Kenji

2012-01-01

Previous studies have indicated that minocycline might function as an antidepressant drug. The aim of this study was to evaluate the antidepressant-like effects of minocycline, which is known to suppress activated microglia, using learned helplessness (LH) rats (an animal model of depression). Infusion of minocycline into the cerebral ventricle of LH rats induced antidepressant-like effects. However, infusion of minocycline into the cerebral ventricle of naïve rats did not produce locomotor activation in the open field tests, suggesting that the antidepressant-like effects of minocycline were not attributed to the enhanced locomotion. LH rats showed significantly higher serotonin turnover in the orbitofrontal cortex and lower levels of brain-derived neurotrophic factor (BDNF) in the hippocampus than control rats. However, these alterations in serotonin turnover and BDNF expression remained unchanged after treatment with minocycline. On the contrary, minocycline treatment of LH rats induced significant increases in the levels of dopamine and its metabolites in the amygdala when compared with untreated LH rats. Taken together, minocycline may be a therapeutic drug for the treatment of depression. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of Minocycline on Extracellular Matrix Metalloproteinase Inducer, a Factor Implicated in Multiple Sclerosis Immunopathogenesis.

PubMed

Hahn, Jennifer N; Kaushik, Deepak K; Mishra, Manoj K; Wang, Jianxiong; Silva, Claudia; Yong, V Wee

2016-11-15

Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that is upregulated on leukocytes in active lesions in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Administration of anti-EMMPRIN Abs reduces the severity of EAE. Minocycline is a tetracycline antibiotic with immune-modulatory properties that decreases the severity of EAE; it was recently found to attenuate the conversion from a first demyelinating event to clinically definite MS in a phase III trial. We investigated whether and how minocycline affects the expression of EMMPRIN on T cells in culture and in mice afflicted with EAE. EMMPRIN expression in cultures of mouse splenocytes or human PBMCs was elevated upon polyclonal T cell activation, and this was reduced by minocycline correspondent with decreased P-Akt levels. An established MS medication, IFN-β, also diminished EMMPRIN levels on human cells whereas this was not readily observed for fingolimod or monomethylfumarate. In EAE-afflicted mice, minocycline treatment significantly reduced EMMPRIN levels on splenic lymphocytes at the presymptomatic (day 7) phase, and prevented the development of disease. Day 7 spleen transcripts from minocycline-treated EAE mice had a significantly lower MMP-9/TIMP-1 ratio, and significantly lower MCT-1 and CD98 levels, factors associated with EMMPRIN function. Day 16 (peak clinical severity) CNS samples from EAE mice had prominent representation of inflammatory perivascular cuffs, inflammatory molecules and EMMPRIN, and these were abrogated by minocycline. Overall, minocycline attenuated the activation-induced elevation of EMMPRIN on T cells in culture and in EAE mice, correspondent with reduced immune function and EAE CNS pathology. Copyright © 2016 by The American Association of Immunologists, Inc.

Imipenem/cilastatin-induced acute eosinophilic pneumonia.

PubMed

Foong, Kap Sum; Lee, Ashley; Pekez, Marijeta; Bin, Wei

2016-03-04

Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid. 2016 BMJ Publishing Group Ltd.

The complexity of minocycline serum protein binding.

PubMed

Zhou, Jian; Tran, Brian T; Tam, Vincent H

2017-06-01

Serum protein binding is critical for understanding the pharmacology of antimicrobial agents. Tigecycline and eravacycline were previously reported to have atypical non-linear protein binding; the percentage of free fraction decreased with increasing total concentration. In this study, we extended the investigation to other tetracyclines and examined the factors that might impact protein binding. Different minocycline concentrations (0.5-50 mg/L) and perfusion media (saline, 0.1 M HEPES buffer and 0.1 and 1 M PBS) were examined by in vitro microdialysis. After equilibration, two dialysate samples were taken from each experiment and the respective antimicrobial agent concentrations were analysed by validated LC-MS/MS methods. For comparison, the serum protein bindings of doxycycline and levofloxacin were also determined. The free fraction of minocycline decreased with increasing total concentration, and the results depended on the perfusion media used. The trends of minocycline protein binding in mouse and human sera were similar. In addition, serum protein binding of doxycycline showed the same concentration-dependent trend as minocycline, while the results of levofloxacin were concentration independent. The serum protein bindings of minocycline and doxycycline are negatively correlated with their total concentrations. It is possible that all tetracyclines share the same pharmacological property. Moreover, the specific perfusion media used could also impact the results of microdialysis. Additional studies are warranted to understand the mechanism(s) and clinical implications of serum protein binding of tetracyclines. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Protective effects of minocycline on the reduction of dopamine transporters in the striatum after administration of methamphetamine: a positron emission tomography study in conscious monkeys.

PubMed

Hashimoto, Kenji; Tsukada, Hideo; Nishiyama, Shingo; Fukumoto, Dai; Kakiuchi, Takeharu; Iyo, Masaomi

2007-03-01

Positron emission tomography (PET) studies of methamphetamine (METH) abusers suggest that psychotic symptoms of METH abusers may be attributable to the reduction of dopamine transporters (DAT) in the human brain. However, there are currently no particular pharmacological treatments for the wide range of symptoms associated with METH abuse. Using a PET study in conscious monkeys, we investigated whether the second generation antibiotic minocycline could protect against the reduction of DAT in monkeys treated with METH (2 mg/kg x 3, 3-hour intervals). Pretreatment and subsequent administration of minocycline significantly attenuated the reduction of DAT in the striatum of monkeys treated with METH. Furthermore, posttreatment and subsequent administration of minocycline also significantly attenuated the reduction of DAT. In contrast, repeated administration of minocycline alone did not alter the density of DAT in the striatum of monkeys treated with METH. Our findings suggest that minocycline protects against METH-induced neurotoxicity in the monkey brain. Therefore, minocycline is likely to be a promising therapeutic agent for the treatment of several symptoms associated with METH use in humans.

Administration of the glial cell modulator, minocycline, in the nucleus accumbens attenuated the maintenance and reinstatement of morphine-seeking behavior.

PubMed

Arezoomandan, Reza; Haghparast, Abbas

2016-03-01

Relapse to drug use is one of the most difficult clinical problems in treating addiction. Glial activation has been linked with the drug abuse, and the glia modulators such as minocycline can modulate the drug abuse effects. The aim of the present study was to determine whether minocycline could attenuate the maintenance and reinstatement of morphine. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) for 3 days. Following the acquisition of the CPP, the rats were given daily bilateral intra-NAc injections of either minocycline (1, 5, and 10 μg/0.5 μL) or saline (0.5 μL). The animals were tested for conditioning score 60 min after each injection. To induce the reinstatement, a priming dose of morphine (1 mg/kg) was injected 1 day after the final extinction day. The morphine-induced CPP lasted for 7 days after cessation of morphine treatment. Our data revealed that a priming dose of morphine could reinstate the extinguished morphine-induced CPP. Daily intra-accumbal injection of minocycline during the extinction period blocked the maintenance of morphine CPP and also attenuated the priming-induced reinstatement. Our findings indicated that minocycline could facilitate the extinction and attenuate the reinstatement of morphine. These results provided new evidence that minocycline might be considered as a promising therapeutic agent for the treatment of several symptoms associated with morphine abuse.

Minocycline reduces neuronal death and attenuates microglial response after pediatric asphyxial cardiac arrest.

PubMed

Tang, Minke; Alexander, Henry; Clark, Robert S B; Kochanek, Patrick M; Kagan, Valerian E; Bayir, Hülya

2010-01-01

The mechanisms leading to delayed neuronal death after asphyxial cardiac arrest (ACA) in the developing brain are unknown. This study aimed at investigating the possible role of microglial activation in neuronal death in developing brain after ACA. Postnatal day-17 rats were subjected to 9 mins of ACA followed by resuscitation. Rats were randomized to treatment with minocycline, (90 mg/kg, intraperitoneally (i.p.)) or vehicle (saline, i.p.) at 1 h after return of spontaneous circulation. Thereafter, minocycline (22.5 mg/kg, i.p.) was administrated every 12 h until sacrifice. Microglial activation (evaluated by immunohistochemistry using ionized calcium-binding adapter molecule-1 (Iba1) antibody) coincided with DNA fragmentation and neurodegeneration in CA1 hippocampus and cortex (assessed by deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL), Fluoro-Jade-B and Nissl stain). Minocycline significantly decreased both the microglial response and neuronal degeneration compared with the vehicle. Asphyxial CA significantly enhanced proinflammatory cytokine and chemokine levels in hippocampus versus control (assessed by multiplex bead array assay), specifically tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), regulated upon activation, normal T-cell expressed and secreted (RANTES), and growth-related oncogene (GRO-KC) (P<0.05). Minocycline attenuated ACA-induced increases in MIP-1alpha and RANTES (P<0.05). These data show that microglial activation and cytokine production are increased in immature brain after ACA. The beneficial effect of minocycline suggests an important role for microglia in selective neuronal death after pediatric ACA, and a possible therapeutic target.

In Vitro Assessment of Combined Polymyxin B and Minocycline Therapy against Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae.

PubMed

Huang, Dennis; Yu, Brenda; Diep, John K; Sharma, Rajnikant; Dudley, Michael; Monteiro, Jussimara; Kaye, Keith S; Pogue, Jason M; Abboud, Cely Saad; Rao, Gauri G

2017-07-01

The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based combination treatments have been reported for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the in vitro activity of polymyxin B and minocycline combination therapy against six KPC-2-producing K. pneumoniae isolates (minocycline MIC range, 2 to 32 mg/liter). Polymyxin B monotherapy (0.5, 1, 2, 4, and 16 mg/liter) resulted in a rapid reduction of up to 6 log in bactericidal activity followed by regrowth by 24 h. Minocycline monotherapy (1, 2, 4, 8, and 16 mg/liter) showed no reduction of activity of >1.34 log against all isolates, although concentrations of 8 and 16 mg/liter prolonged the time to regrowth. When the therapies were used in combination, rapid bactericidal activity was followed by slower regrowth, with synergy (60 of 120 combinations at 24 h, 19 of 120 combinations at 48 h) and additivity (43 of 120 combinations at 24 h, 44 of 120 combinations at 48 h) against all isolates. The extent of killing was greatest against the more susceptible polymyxin B isolates (MICs of ≤0.5 mg/liter) regardless of the minocycline MIC. The pharmacodynamic activity of combined polymyxin B-minocycline therapy against KPC-producing K. pneumoniae is dependent on polymyxin B susceptibility. Further in vitro and animal studies must be performed to fully evaluate the efficacy of this drug combination. Copyright © 2017 American Society for Microbiology.

Minocycline affects human neutrophil respiratory burst and transendothelial migration.

PubMed

Parenti, Astrid; Indorato, Boris; Paccosi, Sara

2017-02-01

This study aimed at investigating the in vitro activity of minocycline and doxycycline on human polymorphonuclear (h-PMN) cell function. h-PMNs were isolated from whole venous blood of healthy subjects; PMN oxidative burst was measured by monitoring ROS-induced oxidation of luminol and transendothelial migration was studied by measuring PMN migration through a monolayer of human umbilical vein endothelial cells. Differences between multiple groups were determined by ANOVA followed by Tukey's multiple comparison test; Student's t test for unpaired data for two groups. Minocycline (1-300 µM) concentration dependently and significantly inhibited oxidative burst of h-PMNs stimulated with 100 nM fMLP. Ten micromolar concentrations, which are superimposable to C max following a standard oral dose of minocycline, promoted a 29.8 ± 4 % inhibition of respiratory burst (P < 0.001; n = 6). Doxycycline inhibited ROS production with a lesser extent and at higher concentrations. 10-100 µM minocycline impaired PMN transendothelial migration, with maximal effect at 100 µM (42.5 ± 7 %, inhibition, n = 5, P < 0.001). These results added new insight into anti-inflammatory effects of minocycline exerted on innate immune h-PMN cell function.

Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy.

PubMed

Vinay, Keshavamurthy; Narang, Tarun; Saikia, Uma N; Kumaran, Muthu Sendhil; Dogra, Sunil

2017-03-01

Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety is limited. We report a series of eight patients who developed persisting injection site granulomatous reaction following Mw immunotherapy and were successfully treated with minocycline. Eight patients with persistent nodular swelling at the site of Mw injections were identified. Seven of them had received Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The lesions were firm, erythematous, succulent, non-tender nodules confined to the sites of Mw vaccine injections. In 6 of these patients nodules also involved the previously injected areas. Skin biopsy from all patients showed eosinophil rich inflammation admixed with histiocytes and lymphocytes. In addition granulomas were seen in all with septal and nodular panniculitis in four patients. Broken and granular acid-fast bacilli were identified in two cases. All patients were treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good clinical response. Granulomatous reaction is a rare but significant adverse effect of Mw immunotherapy at cosmetically and functionally imperative sites. Oral minocycline appears to be effective therapy in this situation. © 2016 Wiley Periodicals, Inc.

Pharmacokinetics and Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Neutropenic Murine Pneumonia Model

PubMed Central

Zhou, Jian; Ledesma, Kimberly R.; Chang, Kai-Tai; Abodakpi, Henrietta; Gao, Song

2017-01-01

ABSTRACT Multidrug-resistant (MDR) Acinetobacter baumannii is increasingly more prevalent in nosocomial infections. Although in vitro susceptibility of A. baumannii to minocycline is promising, the in vivo efficacy of minocycline has not been well established. In this study, the in vivo activity of minocycline was evaluated in a neutropenic murine pneumonia model. Specifically, we investigated the relationship between minocycline exposure and bactericidal activity using five A. baumannii isolates with a broad range of susceptibility (MIC ranged from 0.25 mg/liter to 16 mg/liter). The pharmacokinetics of minocycline (single dose of 25 mg/kg of body weight, 50 mg/kg, 100 mg/kg, and a humanized regimen, given intraperitoneally) in serum and epithelial lining fluid (ELF) were characterized. Dose linearity was observed for doses up to 50 mg/kg and pulmonary penetration ratios (area under the concentration-time curve in ELF from 0 to 24 h [AUCELF,0–24]/area under the concentration time curve in serum from 0 to 24 h [AUCserum,0–24]) ranged from 2.5 to 2.8. Pharmacokinetic-pharmacodynamics (PK-PD) index values in ELF for various dose regimens against different A. baumannii isolates were calculated. The maximum efficacy at 24 h was approximately 1.5-log-unit reduction of pulmonary bacterial burdens from baseline. The AUC/MIC ratio was the PK-PD index most closely correlating to the bacterial burden (r2 = 0.81). The required AUCELF,0–24/MIC for maintaining stasis and achieving 1-log-unit reduction were 140 and 410, respectively. These findings could guide the treatment of infections caused by A. baumannii using minocycline in the future. Additional studies to examine resistance development during therapy are warranted. PMID:28264853

Pharmacokinetics and Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Neutropenic Murine Pneumonia Model.

PubMed

Zhou, Jian; Ledesma, Kimberly R; Chang, Kai-Tai; Abodakpi, Henrietta; Gao, Song; Tam, Vincent H

2017-05-01

Multidrug-resistant (MDR) Acinetobacter baumannii is increasingly more prevalent in nosocomial infections. Although in vitro susceptibility of A. baumannii to minocycline is promising, the in vivo efficacy of minocycline has not been well established. In this study, the in vivo activity of minocycline was evaluated in a neutropenic murine pneumonia model. Specifically, we investigated the relationship between minocycline exposure and bactericidal activity using five A. baumannii isolates with a broad range of susceptibility (MIC ranged from 0.25 mg/liter to 16 mg/liter). The pharmacokinetics of minocycline (single dose of 25 mg/kg of body weight, 50 mg/kg, 100 mg/kg, and a humanized regimen, given intraperitoneally) in serum and epithelial lining fluid (ELF) were characterized. Dose linearity was observed for doses up to 50 mg/kg and pulmonary penetration ratios (area under the concentration-time curve in ELF from 0 to 24 h [AUC ELF,0-24 ]/area under the concentration time curve in serum from 0 to 24 h [AUC serum,0-24 ]) ranged from 2.5 to 2.8. Pharmacokinetic-pharmacodynamics (PK-PD) index values in ELF for various dose regimens against different A. baumannii isolates were calculated. The maximum efficacy at 24 h was approximately 1.5-log-unit reduction of pulmonary bacterial burdens from baseline. The AUC/MIC ratio was the PK-PD index most closely correlating to the bacterial burden ( r 2 = 0.81). The required AUC ELF,0-24 /MIC for maintaining stasis and achieving 1-log-unit reduction were 140 and 410, respectively. These findings could guide the treatment of infections caused by A. baumannii using minocycline in the future. Additional studies to examine resistance development during therapy are warranted. Copyright © 2017 American Society for Microbiology.

Minocycline-induced hyperpigmentation of tympanic membrane, sclera, teeth, and pinna.

PubMed

Reese, Stephen; Grundfast, Kenneth

2015-11-01

A 40-year-old woman was referred by her primary care physician for evaluation after a routine physical exam revealed bilateral brownish pigmentation of the tympanic membrane. Head and neck examination in the otolaryngology clinic revealed bluish hue of both sclera, teeth, and portions of her pinnae. A hearing test revealed bilateral mild sensorineural hearing loss. The patient had a history of taking minocycline for 14 years, and the hyperpigmentation that she had is known to be a rare complication of prolonged minocycline use. However, to our knowledge, this is the first case showing photographic evidence of minocycline-induced tympanic membrane hyperpigmentation. Minocycline-induced hyperpigmentation should be considered when a patient presents with brown or blue discoloration of the tympanic membrane. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

A pilot study on the combination treatment of reduced-fluence photodynamic therapy, intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for neovascular age-related macular degeneration.

PubMed

Sivaprasad, S; Patra, S; DaCosta, J; Adewoyin, T; Shona, O; Pearce, E; Chong, N V

2011-01-01

To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD). Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm(2)) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 μg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 μm. Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was -5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2-6). The mean reduction in the CRT was 66.3 μm (±75). This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD. Copyright © 2011 S. Karger AG, Basel.

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

PubMed

Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

2012-10-25

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

Minocycline in leprosy patients with recent onset clinical nerve function impairment.

PubMed

Narang, Tarun; Arshdeep; Dogra, Sunil

2017-01-01

Nerve function impairment (NFI) in leprosy may occur and progress despite multidrug therapy alone or in combination with corticosteroids. We observed improvement in neuritis when minocycline was administered in patients with type 2 lepra reaction. This prompted us to investigate the role of minocycline in recent onset NFI, especially in corticosteroid unresponsive leprosy patients. Leprosy patients with recent onset clinical NFI (<6 months), as determined by Monofilament Test (MFT) and Voluntary Muscle Test (VMT), were recruited. Minocycline 100mg/day was given for 3 months to these patients. The primary outcome was the proportion of patients with 'restored,' 'improved,' 'stabilized,' or 'deteriorated' NFI. Secondary outcomes included any improvement in nerve tenderness and pain. In this pilot study, 11 patients were recruited. The progression of NFI was halted in all; with 9 out of 11 patients (81.82%) showing ?restored? or ?improved? sensory or motor nerve functions, on assessment with MFT and VMT. No serious adverse effects due to minocycline were observed. Our pilot study demonstrates the efficacy and safety of minocycline in recent onset NFI in leprosy patients. However, larger and long term comparative trials are needed to validate the efficacy of minocycline in leprosy neuropathy. © 2016 Wiley Periodicals, Inc.

A pilot, open-label, 8-week study evaluating the efficacy, safety and tolerability of adjunctive minocycline for the treatment of bipolar I/II depression.

PubMed

Soczynska, Joanna K; Kennedy, Sidney H; Alsuwaidan, Mohammad; Mansur, Rodrigo B; Li, Madeline; McAndrews, Mary Pat; Brietzke, Elisa; Woldeyohannes, Hanna O; Taylor, Valerie H; McIntyre, Roger S

2017-05-01

The objectives of the study were to determine if adjunctive minocycline mitigates depressive symptom severity and improves cognitive function in individuals with bipolar I/II disorder (BD). The study also aimed to determine if changes in depressive and/or cognitive symptoms over the course of treatment were associated with changes in circulating inflammatory cytokine levels. A total of 29 (intention-to-treat: n=27) adults meeting DSM-IV-TR criteria for a major depressive episode as part of bipolar I or II disorder (i.e. Hamilton Depression Rating Scale 17-item [HAMD-17] ≥20) were enrolled in an 8-week, open-label study with adjunctive minocycline (100 mg bid). The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale (MADRS). The HAMD-17, Clinical Global Impression-Severity (CGI-S), cognitive test composite scores and plasma cytokines were secondary outcome measures. Plasma cytokines were measured with the 30 V-Plex Immunoassay from Meso Scale Discovery. Adjunctive minocycline was associated with a reduction in depressive symptom severity from baseline to week 8 on the MADRS (P<.001, d=0.835), HAMD-17 (P<.001, d=0.949) and CGI-S (P<.001, d=1.09). Improvement in psychomotor speed, but not verbal memory or executive function, was observed only amongst individuals exhibiting a reduction in depression severity (P=.007, d=0.826). Levels of interleukin (IL)-12/23p40 (P=.002) were increased, while levels of IL-12p70 (P=.001) and C-C motif chemokine ligand 26 (CCL26) (P<.001) were reduced from baseline to week 8. A reduction in CCL26 levels was associated with a less favourable treatment response (P<.001). Results from the pilot study suggest that adjunctive minocycline may exert antidepressant effects in individuals with bipolar depression, possibly by targeting inflammatory cytokines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Examining the potential preventative effects of minocycline prescribed for acne on the incidence of severe mental illnesses: A historical cohort study.

PubMed

Herrero-Zazo, Maria; Brauer, Ruth; Gaughran, Fiona; Howard, Louise M; Taylor, David; Barlow, David J

2018-05-01

Animal studies suggest that the antibiotic and microglial activation inhibitor, minocycline, is likely to have a protective effect against the emergence of psychosis but evidence from human studies is lacking. The aim of this study is to examine the effects of exposure to minocycline during adolescence on the later incidence of severe mental illness (SMI). A historical cohort study using electronic primary care data was conducted to assess the association between exposure to minocycline during adolescence and incidence of SMI. The Incidence Rate Ratio (IRR) was measured using Poisson regression adjusted for age, gender, time of exposure, socioeconomic deprivation status, calendar year and co-medications. Early minocycline prescription ( n=13,248) did not affect the incidence of SMI compared with non-prescription of minocycline ( n=14,393), regardless of gender or whether or not the data were filtered according to a minimum exposure period (minimum period: IRR 0.96; 95% CI 0.68-1.36; p=0.821; no minimum period: IRR 1.08; 95% CI 0.83-1.42; p=0.566). Exposure to minocycline for acne treatment during adolescence appears to have no effect on the incidence of SMI.

Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

PubMed Central

Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

2008-01-01

Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

Minocycline-Induced Drug Hypersensitivity Syndrome Followed by Multiple Autoimmune Sequelae

PubMed Central

Brown, Rebecca J.; Rother, Kristina I.; Artman, Henry; Mercurio, Mary Gail; Wang, Roger; Looney, R. John; Cowen, Edward W.

2010-01-01

Background Drug hypersensitivity syndrome (DHS) is a severe, multisystem adverse drug reaction that may occur following the use of numerous medications, including anticonvulsants, sulfonamides, and minocycline hydrochloride. Long-term autoimmune sequelae of DHS have been reported, including hypothyroidism. Observations A 15-year-old female adolescent developed DHS 4 weeks after starting minocycline therapy for acne vulgaris. Seven weeks later she developed autoimmune hyperthyroidism (Graves disease), and 7 months after discontinuing minocycline therapy she developed autoimmune type 1 diabetes mellitus. In addition, she developed elevated titers of several markers of systemic autoimmune disease, including antinuclear, anti-Sjögren syndrome A, and anti-Smith antibodies. Conclusions Minocycline-associated DHS may be associated with multiple autoimmune sequelae, including thyroid disease, type 1 diabetes mellitus, and elevated markers of systemic autoimmunity. Long-term follow-up is needed in patients with DHS to determine the natural history of DHS-associated sequelae. PMID:19153345

Minocycline Inhibits Candida albicans Budded-to-Hyphal-Form Transition and Biofilm Formation.

PubMed

Kurakado, Sanae; Takatori, Kazuhiko; Sugita, Takashi

2017-09-25

Candida albicans frequently causes bloodstream infections; its budded-to-hyphalform transition (BHT) and biofilm formation are major contributors to virulence. During an analysis of antibacterial compounds that inhibit C. albicans BHT, we found that the tetracycline derivative minocycline inhibited BHT and subsequent biofilm formation. Minocycline decreased expression of hypha-specific genes HWP1 and ECE1, and adhesion factor gene ALS3 of C. albicans. In addition, minocycline decreased cell surface hydrophobicity and the extracellular β-glucan level in biofilms. Minocycline has been widely used for catheter antibiotic lock therapy to prevent bacterial infection; this compound may also be prophylactically effective against Candida infection.

Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

Contract Number: W81XWH-10-2-0171 TITLE: Minocycline and...30September2012-29September2013 4. TITLE AND SUBTITLE Minocycline and N-acetylcysteine: a synergistic drug combination to treat...grantee previously found screened that the combination of minocycline (MINO) and N-acetyl cysteine (NAC) synergistically improved brain function when

Visualization of drug distribution of topical minocycline in human facial skin with fluorescence microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hermsmeier, Maiko; Sawant, Tanvee; Lac, Diana; Yamamoto, Akira; Chen, Xin; Nagavarapu, Usha; Evans, Conor L.; Chan, Kin Foong

2017-02-01

Minocycline is an antibiotic regularly prescribed to treat acne vulgaris. The only commercially available minocycline comes in an oral dosage form, which often results in systemic adverse effects. A topical minocycline composition (BPX-01) was developed to provide localized and targeted delivery to the epidermis and pilosebaceous unit where acne-related bacteria, Propionibacterium acnes (P. acnes), reside. As minocycline is a known fluorophore, fluorescence microscopy was performed to investigate its potential use in visualizing minocycline distribution within tissues. BPX-01 with various concentrations of minocycline, was applied topically to freshly excised human facial skin specimens. Spatial distribution of minocycline and its fluorescence intensity within the stratum corneum, epidermis, dermis, and pilosebaceous unit were assessed. The resulting fluorescence intensity data as a function of minocycline concentration may indicate clinically relevant therapeutic doses of topical BPX-01 needed to kill P. acnes and reduce inflammation for successful clinical outcomes.

Critical data-based re-evaluation of minocycline as a putative specific microglia inhibitor.

PubMed

Möller, Thomas; Bard, Frédérique; Bhattacharya, Anindya; Biber, Knut; Campbell, Brian; Dale, Elena; Eder, Claudia; Gan, Li; Garden, Gwenn A; Hughes, Zoë A; Pearse, Damien D; Staal, Roland G W; Sayed, Faten A; Wes, Paul D; Boddeke, Hendrikus W G M

2016-10-01

Minocycline, a second generation broad-spectrum antibiotic, has been frequently postulated to be a "microglia inhibitor." A considerable number of publications have used minocycline as a tool and concluded, after achieving a pharmacological effect, that the effect must be due to "inhibition" of microglia. It is, however, unclear how this "inhibition" is achieved at the molecular and cellular levels. Here, we weigh the evidence whether minocycline is indeed a bona fide microglia inhibitor and discuss how data generated with minocycline should be interpreted. GLIA 2016;64:1788-1794. © 2016 Wiley Periodicals, Inc.

Comparison of the Expression Changes after Botulinum Toxin Type A and Minocycline Administration in Lipopolysaccharide-Stimulated Rat Microglial and Astroglial Cultures.

PubMed

Piotrowska, Anna; Popiolek-Barczyk, Katarzyna; Pavone, Flaminia; Mika, Joanna

2017-01-01

Botulinum neurotoxin type A (BoNT/A) and minocycline are potent drugs used in clinical therapies. The primary molecular mechanism of BoNT/A is the cleavage of SNARE proteins, which prevents cells from releasing neurotransmitters from vesicles, while the effects of minocycline are related to the inhibition of p38 activation. Both BoNT/A and minocycline exhibit analgesic effects, however, their direct impact on glial cells is not fully known. Therefore, the aim of the present study was to determine the effects of those drugs on microglial and astroglial activity after lipopolysaccharide (LPS) stimulation and their potential synergistic action. Our results show that BoNT/A and minocycline influenced primary microglial cells by inhibiting intracellular signaling pathways, such as p38, ERK1/2, NF-κB, and the release of pro-inflammatory factors, including IL-1β, IL-18, IL-6, and NOS2. We have revealed that, in contrast to minocycline, BoNT/A treatment did not decrease LPS-induced release of pro-inflammatory factors in the astroglia. In addition, BoNT/A decreased SNAP-23 in both types of glial cells and also SNAP-25 expressed only in astrocytes. Moreover, BoNT/A increased TLR2 and its adaptor protein MyD88, but not TLR4 exclusively in microglial cells. Furthermore, we have shown the impact of BoNT/A on microglial and astroglial cells, with a particular emphasis on its molecular target, TLR2. In contrast, minocycline did not affect any of those factors. We have revealed that despite of different molecular targets, minocycline, and BoNT/A reduced the release of microglia-derived pro-inflammatory factors. In conclusion, we have shown that BoNT/A and minocycline are effective drugs for the management of neuroinflammation by dampening the activation of microglial cells, with minocycline also affecting astroglial activity.

Comparison of the Expression Changes after Botulinum Toxin Type A and Minocycline Administration in Lipopolysaccharide-Stimulated Rat Microglial and Astroglial Cultures

PubMed Central

Piotrowska, Anna; Popiolek-Barczyk, Katarzyna; Pavone, Flaminia; Mika, Joanna

2017-01-01

Botulinum neurotoxin type A (BoNT/A) and minocycline are potent drugs used in clinical therapies. The primary molecular mechanism of BoNT/A is the cleavage of SNARE proteins, which prevents cells from releasing neurotransmitters from vesicles, while the effects of minocycline are related to the inhibition of p38 activation. Both BoNT/A and minocycline exhibit analgesic effects, however, their direct impact on glial cells is not fully known. Therefore, the aim of the present study was to determine the effects of those drugs on microglial and astroglial activity after lipopolysaccharide (LPS) stimulation and their potential synergistic action. Our results show that BoNT/A and minocycline influenced primary microglial cells by inhibiting intracellular signaling pathways, such as p38, ERK1/2, NF-κB, and the release of pro-inflammatory factors, including IL-1β, IL-18, IL-6, and NOS2. We have revealed that, in contrast to minocycline, BoNT/A treatment did not decrease LPS-induced release of pro-inflammatory factors in the astroglia. In addition, BoNT/A decreased SNAP-23 in both types of glial cells and also SNAP-25 expressed only in astrocytes. Moreover, BoNT/A increased TLR2 and its adaptor protein MyD88, but not TLR4 exclusively in microglial cells. Furthermore, we have shown the impact of BoNT/A on microglial and astroglial cells, with a particular emphasis on its molecular target, TLR2. In contrast, minocycline did not affect any of those factors. We have revealed that despite of different molecular targets, minocycline, and BoNT/A reduced the release of microglia-derived pro-inflammatory factors. In conclusion, we have shown that BoNT/A and minocycline are effective drugs for the management of neuroinflammation by dampening the activation of microglial cells, with minocycline also affecting astroglial activity. PMID:28491822

Minocycline enhances inhibitory transmission to substantia gelatinosa neurons of the rat spinal dorsal horn.

PubMed

Peng, H-Z; Ma, L-X; Lv, M-H; Hu, T; Liu, T

2016-04-05

Minocycline, a second-generation tetracycline, is well known for its antibiotic, anti-inflammatory, and antinociceptive effects. Modulation of synaptic transmission is one of the analgesic mechanisms of minocycline. Although it has been reported that minocycline may suppress excitatory glutamatergic synaptic transmission, it remains unclear whether it could affect inhibitory synaptic transmission, which also plays a key role in modulating pain signaling. To examine the effect of minocycline on synaptic transmission in rat spinal substantia gelatinosa (SG) neurons, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole-cell patch-clamp recording at a holding potential of 0 mV. Bath application of minocycline significantly increased the frequency but not the amplitude of sIPSCs in a reversible and concentration-dependent manner with an EC50 of 85. The enhancement of inhibitory synaptic transmission produced by minocycline was not affected by the glutamate receptor antagonists CNQX and D-APV or by the voltage-gated sodium channel blocker tetrodotoxin (TTX). Moreover, the potency of minocycline for facilitating sIPSC frequency was the same in both glycinergic and GABAergic sIPSCs without changing their decay phases. However, the facilitatory effect of minocycline on sIPSCs was eliminated in a Ca(2+)-free Krebs solution or by co-administration with calcium channel blockers. In summary, our data demonstrate that baseline inhibitory synaptic transmission in SG neurons is markedly enhanced by minocycline. This may function to decrease the excitability of SG neurons, thus leading to a modulation of nociceptive transmission. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

PubMed

Kumar, Hariom; Sharma, Bhupesh

2016-01-01

Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism. Copyright © 2015 Elsevier B.V. All rights reserved.

Rabeprazole, Minocycline, Amoxicillin, and Bismuth as First-Line and Second-Line Regimens for Helicobacter pylori Eradication.

PubMed

Song, Zhiqiang; Suo, Baojun; Zhang, Lingyun; Zhou, Liya

2016-12-01

Because of general unavailability of tetracycline, common adverse effects, and complicated administration, the clinical application of bismuth quadruple therapy often faces difficulties. Whether the combination of minocycline and amoxicillin can replace tetracycline and metronidazole for Helicobacter pylori eradication remains unclear. This study was to determine the efficacy, compliance, and safety of rabeprazole, minocycline, amoxicillin, and bismuth (RMAB) therapy as first-line and second-line regimens. Between July 2013 and December 2015, a total of 160 patients in first-line and 70 patients in second-line therapies received rabeprazole 10 mg, minocycline 100 mg, amoxicillin 1000 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. Eradication status was assessed 6-12 weeks after treatment. RMAB therapy achieved the eradication rates of 87.5% (95% confidence interval, 81.9-92.5%, intention-to-treat analysis), 90.9% (85.7-95.5%, modified intention-to-treat analysis), and 92.6% (88.5-96.6%, per-protocol analysis) in first-line therapy in a setting with high antibiotic resistance rates (amoxicillin 3.4%, clarithromycin 39.7%, metronidazole 60.3%, levofloxacin 36.2%, tetracycline 3.4%, and minocycline 6.9%). As for second-line therapy, the eradication rates were 82.9% (74.3-91.4%, intention-to-treat analysis), 86.6% (77.6-94.0%, modified intention-to-treat analysis), and 89.1% (81.3-95.3%, per-protocol analysis). Totally, 24.0% patients had adverse effects, 2.2% discontinued medications, and good compliance was achieved in 94.7%. Poor compliance and minocycline resistance were identified as the risk factors for treatment failure. Significant differences in efficacy existed among the groups of both sensitive (48/51 and 18/20), isolated amoxicillin resistance (1/1 and 0/0), isolated minocycline resistance (2/3 and 1/1), and dual resistance (0/1 and 0/1) in both first-line (p = .004) and second-line (p = .035) therapies. The eradication efficacies of RMAB

Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury

DTIC Science & Technology

2011-10-01

AD_________________ Award Number: W81XWH-10-2-0171 TITLE: Minocycline and N-acetylcysteine: A... Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury 5b. GRANT NUMBER W81XWH-10-2-0171 5c. PROGRAM...combination of minocycline (MINO) and N-acetyl cysteine (NAC) synergistically improved brain function when dosed one hour following closed cortical

Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy.

PubMed

Miranda, H F; Sierralta, F; Jorquera, V; Poblete, P; Prieto, J C; Noriega, V

2017-02-01

Diabetic neuropathy (DN) is the most common complication of diabetes and pain is one of the main symptoms of diabetic neuropathy, however, currently available drugs are often ineffective and complicated by adverse events. The purpose of this research was to evaluate the antinociceptive interaction between gabapentin and minocycline in a mice experimental model of DN by streptozocin (STZ). The interaction of gabapentin with minocycline was evaluated by the writhing and hot plate tests at 3 and 7 days after STZ injection or vehicle in male CF1 mice. STZ (150 mg/kg, i.p.) produced a marked increase in plasma glucose levels on day 7 (397.46 ± 29.65 mg/dL) than on day 3 (341.12 ± 35.50 mg/dL) and also developed neuropathic pain measured by algesiometric assays. Gabapentin produced similar antinociceptive activity in both writhing and hot plate tests in mice pretreated with STZ. However, minocycline was more potent in the writhing than in the hot plate test in the same type of mice. The combination of gabapentin with minocycline produced synergistic interaction in both test. The combination of gabapentin with minocycline in a 1:1 proportion fulfills all the criteria of multimodal analgesia and this finding suggests that the combination provide a therapeutic alternative that could be used for human neuropathic pain management.

Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

PubMed

Tang, Jun; Chen, Qianwei; Guo, Jing; Yang, Liming; Tao, Yihao; Li, Lin; Miao, Hongping; Feng, Hua; Chen, Zhi; Zhu, Gang

2016-04-01

Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

PubMed Central

Song, Zhen-peng; Xiong, Bing-rui; Guan, Xue-hai; Cao, Fei; Manyande, Anne; Zhou, Ya-qun; Zheng, Hua; Tian, Yu-ke

2016-01-01

Aim: To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. Methods: A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. Results: BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Conclusion: Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes. PMID:27157092

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes.

PubMed

Song, Zhen-Peng; Xiong, Bing-Rui; Guan, Xue-Hai; Cao, Fei; Manyande, Anne; Zhou, Ya-Qun; Zheng, Hua; Tian, Yu-Ke

2016-06-01

To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

Minocycline combination therapy with fluvoxamine in moderate-to-severe obsessive-compulsive disorder: A placebo-controlled, double-blind, randomized trial.

PubMed

Esalatmanesh, Sophia; Abrishami, Zoha; Zeinoddini, Atefeh; Rahiminejad, Fatemeh; Sadeghi, Majid; Najarzadegan, Mohammad-Reza; Shalbafan, Mohammad-Reza; Akhondzadeh, Shahin

2016-11-01

Several lines of evidence implicate glutamatergic dysfunction in the pathophysiology of obsessive-compulsive disorder (OCD), presenting this neurotransmitter as a target for the development of novel pharmacotherapy. The objective of this study was to assess the efficacy of minocycline as an augmentative agent to fluvoxamine in the treatment of patients with OCD. One hundred and two patients with the diagnosis of moderate-to-severe OCD were recruited to this study. A randomized double-blind trial was designed and patients received either L-carnosine or placebo as adjuvant to fluvoxamine for 10 weeks. The patients randomly received either minocycline 100 mg twice per day or placebo for 10 weeks. All patients received fluvoxamine (100 mg/day) for the first 4 weeks, followed by 200 mg/day for the rest of the trial, regardless of their treatment groups. Participants were evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The main outcome measure was to assess the efficacy of minocycline in improving the OCD symptoms. General linear model repeated measures demonstrated significant effect for time × treatment interaction on the Y-BOCS total scores, F(1.49, 137.93) = 7.1, P  = 0.003, and Y-BOCS Obsession subscale score, F(1.54, 141.94) = 9.72, P = 0.001, and near significant effect for the Y-BOCS Compulsion subscale score, F(1.27, 117.47) = 2.92, P  = 0.08. A significantly greater rate of partial and complete response was observed in the minocycline group (P < 0.001). The frequency of side-effects was not significantly different between the treatment arms. The results of this study suggest that minocycline could be a tolerable and effective adjuvant in the management of patients with OCD. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury

DTIC Science & Technology

2012-10-01

W81XWH-10-2-0171 TITLE: Minocycline and N-acetylcysteine: a synergistic drug combination to treat traumatic brain injury PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Minocycline and N-acetylcysteine: a synergistic drug combination to treat traumatic brain injury 5a. CONTRACT NUMBER 5b...The grantee previously found screened that the combination of minocycline (MINO) and N-acetyl cysteine (NAC) synergistically improved brain function

High MMP-9 activity levels in fragile X syndrome are lowered by minocycline.

PubMed

Dziembowska, Magdalena; Pretto, Dalyir I; Janusz, Aleksandra; Kaczmarek, Leszek; Leigh, Mary Jacena; Gabriel, Nielsen; Durbin-Johnson, Blythe; Hagerman, Randi J; Tassone, Flora

2013-08-01

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by lack of the FMR1 protein, FMRP, a translational repressor. Its absence leads to up-regulation of locally translated proteins involved in synaptic transmission and plasticity, including the matrix metalloproteinase-9 (MMP-9). In the Fmr1 knock-out (KO), a mouse model of FXS, an abnormal elevated expression of MMP-9 in the brain was pharmacologically down-regulated after treatment with the tetracycline derivative minocycline. Moreover, the rescue of immature dendritic spine morphology and a significant improvement of abnormal behavior were associated with down-regulation of MMP-9. Here, we report on high plasma activity of MMP-9 in individuals with FXS. In addition, we investigate MMP-9 changes in patients with FXS who have gone through a minocycline controlled clinical trial and correlate MMP-9 activity to clinical observations. The results of this study suggest that, in humans, activity levels of MMP-9 are lowered by minocycline and that, in some cases, changes in MMP-9 activity are positively associated with improvement based on clinical measures. Copyright © 2013 Wiley Periodicals, Inc.

Determination of the toxicity of intravitreal minocycline in rabbit eyes.

PubMed

Falavarjani, Khalil Ghasemi; Pourhabibi, Arash; Aghdam, Kaveh Abri; Hosseini, Seyed Bagher; Modarres, Mehdi; Pazouki, Abdolreza; Khanamiri, Hossein Nazari

2016-09-01

To evaluate the retinal toxicity of intravitreal minocycline in rabbit eyes. Intravitreal injection of minocycline with concentrations of 1000, 500, 250, 125 and 62.5 μg in 0.1 ml was performed in 10 New Zealand albino rabbits. Each concentration was injected into two rabbit eyes. For each dose, normal saline was injected in one contralateral eye and the other fellow eye remained non-injected. Electrophysiologic testing was performed before and 4 weeks after injections. The eyes were enucleated 4 weeks after injections and examined using light microscopy. The clinical examination was unremarkable after injections. Electroretinography recordings were significantly affected at all doses in at least one of the a- or b-waves of photopic or scotopic responses. Histopathologic examination revealed marked atrophy and loss of integrity in all retinal layers in all minocycline injected eyes. Contralateral eyes were normal. In our study, intravitreal minocycline was toxic to the retina in albino rabbits even at a concentration of 62.5 µg/0.1 ml.

Activated Microglia Targeting Dendrimer-Minocycline Conjugate as Therapeutics for Neuroinflammation.

PubMed

Sharma, Rishi; Kim, Soo-Young; Sharma, Anjali; Zhang, Zhi; Kambhampati, Siva Pramodh; Kannan, Sujatha; Kannan, Rangaramanujam M

2017-11-15

Brain-related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Minocycline has shown promise for the treatment of neurological diseases owing to its ability to penetrate the blood-brain barrier (BBB) and potency. Despite its potential in the clinic and in preclinical models, the high doses needed to affect a positive therapeutic response have led to side effects. Targeted delivery of minocycline to the injured site and injured cells in the brain can be highly beneficial. Systemically administered hydroxyl poly(amidoamine) (PAMAM) generation-6 (G6) dendrimers have a longer blood circulation time and have been shown to cross the impaired BBB. We have successfully prepared and characterized the in vitro efficacy and in vivo targeting ability of hydroxyl-G6 PAMAM dendrimer-9-amino-minocycline conjugate (D-mino). Minocycline is a challenging drug to carry out chemical transformations due to its inherent instability. We used a combination of a highly efficient and mild copper catalyzed azide-alkyne click reaction (CuAAC) along with microwave energy to conjugate 9-amino-minocycline (mino) to the dendrimer surface via enzyme responsive linkages. D-mino was further evaluated for anti-inflammatory and antioxidant activity in lipopolysaccharides-activated murine microglial cells. D-mino conjugates enhanced the intracellular availability of the drug due to their rapid uptake, suppressed inflammatory cytokine tumor necrosis factor α (TNF-α) production, and reduced oxidative stress by suppressing nitric oxide production, all significantly better than the free drug. Fluorescently labeled dendrimer conjugate (Cy5-D-mino) was systematically administered (intravenous, 55 mg/kg) on postnatal

Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion-Related Ischemia.

PubMed

Drenger, Benjamin; Fellig, Yakov; Ben-David, Dror; Mintz, Bella; Idrees, Suhel; Or, Omer; Kaplan, Leon; Ginosar, Yehuda; Barzilay, Yair

2016-04-01

To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. Tertiary medical center and school of medicine laboratory. Laboratory animals-rabbits. Balloon obstruction of infrarenal aorta introduced via femoral artery incision. Severe hindlimb paralysis (mean Tarlov score 0.36±0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58±0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord. Copyright © 2016. Published by Elsevier Inc.

Stabilization of endogenous Nrf2 by minocycline protects against Nlrp3-inflammasome induced diabetic nephropathy.

PubMed

Shahzad, Khurrum; Bock, Fabian; Al-Dabet, Moh'd Mohanad; Gadi, Ihsan; Nazir, Sumra; Wang, Hongjie; Kohli, Shrey; Ranjan, Satish; Mertens, Peter R; Nawroth, Peter P; Isermann, Berend

2016-10-10

While a plethora of studies support a therapeutic benefit of Nrf2 activation and ROS inhibition in diabetic nephropathy (dNP), the Nrf2 activator bardoxolone failed in clinical studies in type 2 diabetic patients due to cardiovascular side effects. Hence, alternative approaches to target Nrf2 are required. Intriguingly, the tetracycline antibiotic minocycline, which has been in clinical use for decades, has been shown to convey anti-inflammatory effects in diabetic patients and nephroprotection in rodent models of dNP. However, the mechanism underlying the nephroprotection remains unknown. Here we show that minocycline protects against dNP in mouse models of type 1 and type 2 diabetes, while caspase -3,-6,-7,-8 and -10 inhibition is insufficient, indicating a function of minocycline independent of apoptosis inhibition. Minocycline stabilizes endogenous Nrf2 in kidneys of db/db mice, thus dampening ROS-induced inflammasome activation in the kidney. Indeed, minocycline exerts antioxidant effects in vitro and in vivo, reducing glomerular markers of oxidative stress. Minocycline reduces ubiquitination of the redox-sensitive transcription factor Nrf2 and increases its protein levels. Accordingly, minocycline mediated Nlrp3 inflammasome inhibition and amelioration of dNP are abolished in diabetic Nrf2 -/- mice. Taken together, we uncover a new function of minocycline, which stabilizes the redox-sensitive transcription factor Nrf2, thus protecting from dNP.

A Monte Carlo pharmacokinetic/pharmacodynamic simulation to evaluate the efficacy of minocycline, tigecycline, moxifloxacin, and levofloxacin in the treatment of hospital-acquired pneumonia caused by Stenotrophomonas maltophilia.

PubMed

Wei, Chuanqi; Ni, Wentao; Cai, Xuejiu; Cui, Junchang

2015-01-01

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in recent years. Increasing antimicrobial resistance and other contraindications have greatly compromised trimethoprim/sulfamethoxazole (SXT) as the first-line therapeutic option. The objective of this study was to explore other options for treating hospital-acquired pneumonia (HAP) caused by S. maltophilia. A total of 102 strains of S. maltophilia were isolated from sputum and bronchoalveolar lavage (BAL) specimens of patients with HAP in our institution. The minimum inhibitory concentration (MIC) values of minocycline, tigecycline, moxifloxacin, and levofloxacin were determined by the agar dilution method. Based on the MICs and the population pharmacokinetic parameters of the investigated antimicrobials, a Monte Carlo simulation was performed to simulate the pharmacokinetic/pharmacodynamic (PK/PD) indices of different regimens. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens. The susceptibility rates to minocycline, tigecycline, moxifloxacin, and levofloxacin were 96.1%, 80.4%, 74.5%, and 69.6%, respectively. The estimated CFRs were 96.2% for minocycline 100 mg twice daily; 50.8%/67.1%/75.4% for tigecycline 50/75/100 mg twice daily; 34.3%/48.0%/56.6% for levofloxacin 500/750/1000 mg once daily; and 45.7% for moxifloxacin 400 mg once daily. The simulation results suggest that minocycline may be a proper choice for treatment of HAP caused by S. maltophilia, while tigecycline, moxifloxacin, and levofloxacin may not be optimal as monotherapy.

Minocycline reduces inflammatory parameters in the brain structures and serum and reverses memory impairment caused by the administration of amyloid β (1-42) in mice.

PubMed

Garcez, Michelle Lima; Mina, Francielle; Bellettini-Santos, Tatiani; Carneiro, Franciellen Gonçalves; Luz, Aline Pereira; Schiavo, Gustavo Luis; Andrighetti, Matheus Scopel; Scheid, Maylton Grégori; Bolfe, Renan Pereira; Budni, Josiane

2017-07-03

Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of age-related dementia. Cognitive decline, beta-amyloid (Aβ) accumulation, neurofibrillary tangles, and neuroinflammation are the main pathophysiological characteristics of AD. Minocycline is a tetracycline derivative with anti-inflammatory properties that has a neuroprotective effect. The aim of this study was to evaluate the effect of minocycline on memory, neurotrophins and neuroinflammation in an animal model of AD induced by the administration of Aβ (1-42) oligomer. Male BALB/c mice were treated with minocycline (50mg/kg) via the oral route for a total of 17days, 24h after intracerebroventricular administration of Aβ (1-42) oligomer. At the end of this period, was performed the radial maze test, and 24h after the last minocycline administration, serum was collected and the cortex and hippocampus were dissected for biochemical analysis. The administration of minocycline reversed the memory impairment caused by Aβ (1-42). In the hippocampus, minocycline reversed the increases in the levels of interleukin (IL-1β), Tumor Necrosis Factor- alpha (TNF-α) and, IL-10 caused by Aβ (1-42). In the cortex, AD-like model increase the levels of IL-1β, TNF-α and, IL-4. Minocycline treatment reversed this. In the serum, Aβ (1-42) increased the levels of IL-1β and IL-4, and minocycline was able to reverse this action, but not to reverse the decrease of IL-10 levels. Minocycline also reversed the increase in the levels of Brain-derived neurotrophic factor (BDNF) in the hippocampus caused by Aβ (1-42), and reduced Nerve Growth Factor (NGF) increases in the total cortex. Therefore, our results indicate that minocycline causes improvements in the spatial memory, and cytokine levels were correlated with this effect in the brain it. Besides this, minocycline reduced BDNF and NGF levels, highlighting the promising effects of minocycline in treating AD-like dementia. Copyright © 2017

Neuroprotective effects of pretreatment with minocycline on memory impairment following cerebral ischemia in rats.

PubMed

Naderi, Yazdan; Sabetkasaei, Masoumeh; Parvardeh, Siavash; Moini Zanjani, Taraneh

2017-04-01

Cerebral ischemia leads to memory impairment that is associated with loss of hippocampal CA1 pyramidal neurons. Neuroinflammation and oxidative stress may be implicated in the pathogenesis of ischemia/reperfusion damage. Minocycline has anti-inflammatory and antioxidant properties. We investigated the neuroprotective effects of minocycline in rats subjected to cerebral ischemia/reperfusion injury. Thirty male rats were divided into three groups: control, sham, and minocycline-pretreated group. Minocycline (40 mg/kg) was injected intraperitoneally immediately before surgery, and then ischemia was induced by occlusion of common carotid arteries for 20 min. Seven days after reperfusion, the Morris water-maze task was used to evaluate memory. Nissl staining was also performed to analyze pyramidal cell damage. We measured the contents of malondialdehyde and proinflammatory cytokines in the hippocampus by the thiobarbituric acid method and enzyme-linked immunosorbent assay, respectively. Microglial activation was also investigated by Iba1 immunostaining. The results showed that pretreatment with minocycline prevented memory impairment induced by cerebral ischemia/reperfusion. Minocycline pretreatment also significantly attenuated ischemia-induced pyramidal cell death and microglial activation in the CA1 region and reduced the levels of malondialdehyde and proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the hippocampus of ischemic rats. Minocycline showed neuroprotective effects on cerebral ischemia-induced memory deficit probably through its anti-inflammatory and antioxidant activities.

Effectiveness of minocycline and FK506 alone and in combination on enhanced behavioral and biochemical recovery from spinal cord injury in rats.

PubMed

Ahmad, Mohammad; Zakaria, Abdulrahim; Almutairi, Khalid M

2016-06-01

Injury to the spinal cord results in immediate physical damage (primary injury) followed by a prolonged posttraumatic inflammatory disorder (secondary injury). The present study aimed to investigate the neuroprotective effects of minocycline and FK506 (Tacrolimus) individually and in combination on recovery from experimental spinal cord injury (SCI). Young adult male rats were subjected to experimental SCI by weight compression method. Minocycline (50mg/kg) and FK506 (1mg/kg) were administered orally in combination and individually to the SCI group daily for three weeks. During these three weeks, the recovery was measured using behavioral motor parameters (including BBB, Tarlov and other scorings) every other day for 29days after SCI. Thereafter, the animals were sacrificed and the segment of the spinal cord centered at the injury site was removed for the histopathological studies as well as for biochemical analysis of monoamines such as 5-hydroxytryptamine (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) and some oxidative stress indices, such as thiobarbituric acid-reactive substances (TBARS), total glutathione (GSH) and myeloperoxidase (MPO). All behavioral results indicated that both drugs induced significant recovery from SCI with respect to time. The biochemical and histopathological results supported the behavioral findings, revealing significant recovery in the regeneration of the injured spinal tissues, the monoamine levels, and the oxidative stress indices. Overall, the effects of the tested drugs for SCI recovery were as follows: FK506+minocycline>minocycline>FK506 in all studied parameters. Thus, minocycline and FK506 may prove to be a potential therapy cocktail to treat acute SCI. However, further studies are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Minocycline promotes the generation of dendritic cells with regulatory properties.

PubMed

Kim, Narae; Park, Chan-Su; Im, Sun-A; Kim, Ji-Wan; Lee, Jae-Hee; Park, Young-Jun; Song, Sukgil; Lee, Chong-Kil

2016-08-16

Minocycline, which has long been used as a broad-spectrum antibiotic, also exhibits non-antibiotic properties such as inhibition of inflammation and angiogenesis. In this study, we show that minocycline significantly enhances the generation of dendritic cells (DCs) from mouse bone marrow (BM) cells when used together with GM-CSF and IL-4. DCs generated from BM cells in the presence of minocycline (Mino-DCs) demonstrate the characteristics of regulatory DCs. Compared with control DCs, Mino-DCs are resistant to subsequent maturation stimuli, impaired in MHC class II-restricted exogenous Ag presentation, and show decreased cytokine secretion. Mino-DCs also show decreased ability to prime allogeneic-specific T cells, while increasing the expansion of CD4+CD25+Foxp3+ T regulatory cells both in vitro and in vivo. In addition, pretreatment with MOG35-55 peptide-pulsed Mino-DCs ameliorates clinical signs of experimental autoimmune encephalitis induced by MOG peptide injection. Our study identifies minocycline as a new pharmacological agent that could be potentially used to increase the production of regulatory DCs for cell therapy to treat autoimmune disorders, allergy, and transplant rejection.

Mitochondrial Permeability Transition in Pathogenesis of Hemorrhagic Injury: Targeted Therapy with Minocycline

DTIC Science & Technology

2012-03-01

minocy- cline treatment (Figures 1-4). Minocycline also improved mitochondrial function as assessed by intravital multiphoton imaging of the...will make direct measurements by intravital multiphoton microscopy to determine whether onset of the mitochondrial permeability transition and...oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization were assessed by intravital microscopy. After H/R with vehicle or

Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants.

PubMed

Samour, Mohamad Samir; Nagi, Saad Saulat; Shortland, Peter John; Mahns, David Anthony

2017-08-01

-treated participants showed cold allodynia. This study showed that repeated injections of HS can induce a hypersensitivity that outlasts the acute response, and the development of this hypersensitivity can be reliably attenuated with minocycline pretreatment. Four repeated injections of HS at 48-hour intervals induce a state of persistent hypersensitivity in healthy human participants. This hypersensitivity was characterized by bilateral muscular hyperalgesia and cutaneous cold allodynia, symptoms commonly reported in many chronic pain conditions. Minocycline pretreatment abolished the development of this state. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Neuroprotective effect of minocycline on cognitive impairments induced by transient cerebral ischemia/reperfusion through its anti-inflammatory and anti-oxidant properties in male rat.

PubMed

Naderi, Yazdan; Sabetkasaei, Masoumeh; Parvardeh, Siavash; Zanjani, Taraneh Moini

2017-05-01

Memory deficit is the most visible symptom of cerebral ischemia that is associated with loss of pyramidal cells in CA1 region of the hippocampus. Oxidative stress and inflammation may be involved in the pathogenesis of ischemia/reperfusion (I/R) damage. Minocycline, a semi-synthetic tetracycline derived antibiotic, has anti-inflammatory and antioxidant properties. We evaluated the neuroprotective effect of minocycline on memory deficit induced by cerebral I/R in rat. I/R was induced by occlusion of common carotid arteries for 20min. Minocycline (40mg/kg, i.p.) was administered once daily for 7days after I/R. Learning and memory were assessed using the Morris water maze test. Nissl staining was used to evaluate the viability of CA1 pyramidal cells. The effects of minocycline on the microglial activation was also investigated by Iba1 (Ionized calcium binding adapter molecule 1) immunostaining. The content of malondialdehyde (MDA) and pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus were measured by thiobarbituric acid reaction substances method and ELISA, respectively. Minocycline reduced the increase in escape latency time and in swimming path length induced by cerebral I/R. Furthermore, the ischemia-induced reduction in time spent in the target quadrant during the probe trial was increased by treatment with minocycline. Histopathological results indicated that minocycline prevented pyramidal cells death and microglial activation induced by I/R. Minocycline also reduced the levels of MDA and pro-inflammatory cytokines in the hippocampus in rats subjected to I/R. Minocycline has neuroprotective effects on memory deficit induced by cerebral I/R in rat, probably via its anti-inflammatory and antioxidant properties. Copyright © 2017 Elsevier Inc. All rights reserved.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

PubMed

Metz, Luanne M; Li, David K B; Traboulsee, Anthony L; Duquette, Pierre; Eliasziw, Misha; Cerchiaro, Graziela; Greenfield, Jamie; Riddehough, Andrew; Yeung, Michael; Kremenchutzky, Marcelo; Vorobeychik, Galina; Freedman, Mark S; Bhan, Virender; Blevins, Gregg; Marriott, James J; Grand'Maison, Francois; Lee, Liesly; Thibault, Manon; Hill, Michael D; Yong, V Wee

2017-06-01

On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis. During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T 2 -weighted MRI, cumulative number of new lesions enhanced on T 1 -weighted MRI ["enhancing lesions"], and cumulative combined number of unique lesions [new enhancing lesions on T 1 -weighted MRI plus new and newly enlarged lesions on T 2 -weighted MRI]). A total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval [CI], 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95

Sciatic Nerve Intrafascicular Lidocaine Injection-induced Peripheral Neuropathic Pain: Alleviation by Systemic Minocycline Administration.

PubMed

Cheng, Kuang-I; Wang, Hung-Chen; Wu, Yi-Chia; Tseng, Kuang-Yi; Chuang, Yi-Ta; Chou, Chao-Wen; Chen, Ping-Luen; Chang, Lin-Li; Lai, Chung-Sheng

2016-06-01

Peripheral nerve block guidance with a nerve stimulator or echo may not prevent intrafascicular injury. This study investigated whether intrafascicular lidocaine induces peripheral neuropathic pain and whether this pain can be alleviated by minocycline administration. A total of 168 male Sprague-Dawley rats were included. In experiment 1, 2% lidocaine (0.1 mL) was injected into the left sciatic nerve. Hindpaw responses to thermal and mechanical stimuli, and sodium channel and activating transcription factor (ATF-3) expression in dorsal root ganglion (DRG) and glial cells in the spinal dorsal horn (SDH), were measured on days 4, 7, 14, 21, and 28. On the basis of the results in experiment 1, rats in experiment 2 were divided into sham, extraneural, intrafascicular, peri-injury minocycline, and postinjury minocycline groups. Behavioral responses, macrophage recruitment, expression changes of myelin basic protein and Schwann cells in the sciatic nerve, dysregulated expression of ATF-3 in the DRG, and activated glial cells in L5 SDH were assessed on days 7 and 14. Intrafascicular lidocaine induced mechanical allodynia, downregulated Nav1.8, increased ATF-3 expression in the DRG, and activated glial cells in the SDH. Increased expression of macrophages, Schwann cells, and myelin basic protein was found in the sciatic nerve. Minocycline attenuated intrafascicular lidocaine-induced neuropathic pain and nerve damage significantly. Peri-injury minocycline was better than postinjury minocycline administration in alleviating mechanical behaviors, mitigating macrophage recruitment into the sciatic nerve, and suppressing activated microglial cells in the spinal cord. Systemic minocycline administration alleviates intrafascicular lidocaine injection-induced peripheral nerve damage.

Minocycline attenuates colistin-induced neurotoxicity via suppression of apoptosis, mitochondrial dysfunction and oxidative stress

PubMed Central

Dai, Chongshan; Ciccotosto, Giuseppe D.; Cappai, Roberto; Wang, Yang; Tang, Shusheng; Xiao, Xilong; Velkov, Tony

2017-01-01

Background: Neurotoxicity is an adverse effect patients experience during colistin therapy. The development of effective neuroprotective agents that can be co-administered during polymyxin therapy remains a priority area in antimicrobial chemotherapy. The present study investigates the neuroprotective effect of the synergistic tetracycline antibiotic minocycline against colistin-induced neurotoxicity. Methods: The impact of minocycline pretreatment on colistin-induced apoptosis, caspase activation, oxidative stress and mitochondrial dysfunction were investigated using cultured mouse neuroblastoma-2a (N2a) and primary cortical neuronal cells. Results: Colistin-induced neurotoxicity in mouse N2a and primary cortical cells gives rise to the generation of reactive oxygen species (ROS) and subsequent cell death via apoptosis. Pretreatment of the neuronal cells with minocycline at 5, 10 and 20 μM for 2 h prior to colistin (200 μM) exposure (24 h), had an neuroprotective effect by significantly decreasing intracellular ROS production and by upregulating the activities of the anti-ROS enzymes superoxide dismutase and catalase. Minocycline pretreatment also protected the cells from colistin-induced mitochondrial dysfunction, caspase activation and subsequent apoptosis. Immunohistochemical imaging studies revealed colistin accumulates within the dendrite projections and cell body of primary cortical neuronal cells. Conclusions: To our knowledge, this is first study demonstrating the protective effect of minocycline on colistin-induced neurotoxicity by scavenging of ROS and suppression of apoptosis. Our study highlights that co-administration of minocycline kills two birds with one stone: in addition to its synergistic antimicrobial activity, minocycline could potentially ameliorate unwanted neurotoxicity in patients undergoing polymyxin therapy. PMID:28204513

Minocycline added to subcutaneous interferon β-1a in multiple sclerosis: randomized RECYCLINE study.

PubMed

Sørensen, P S; Sellebjerg, F; Lycke, J; Färkkilä, M; Créange, A; Lund, C G; Schluep, M; Frederiksen, J L; Stenager, E; Pfleger, C; Garde, E; Kinnunen, E; Marhardt, K

2016-05-01

Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. Minocycline showed no statistically significant beneficial effect when added to sc IFN β-1a therapy. © 2016 EAN.

Clinical impact of minocycline on afatinib-related rash in patients with non-small cell lung cancer harboring epidermal growth factor receptor mutations.

PubMed

Goto, Ayano; Ozawa, Yuichi; Koda, Keigo; Akahori, Daisuke; Koyauchi, Takashi; Amano, Yusuke; Kakutani, Takuya; Sato, Yoshiko; Hasegawa, Hirotsugu; Matsui, Takashi; Yokomura, Koshi; Suda, Takafumi

2018-03-01

The management of skin toxicity is crucial for efficient afatinib treatment, but the role of tetracycline class antibiotics (TCs) in managing these rashes is relatively unknown. We reviewed the clinical records of patients who were administered afatinib for the treatment of non-small cell lung cancer harboring epidermal growth factor receptor mutations between October 2014 and November 2016. Twenty-five patients, who received TCs for the management of afatinib-related skin disorders, were enrolled. Minocycline was administered orally to participants. Afatinib-related toxic effects, such as rash, diarrhea, and paronychia, were observed in 92%, 92%, and 40% of cases, respectively. Although 24% of diarrhea and 4% of paronychia cases were rated grade 3 or higher, no severe cases of rash were observed during afatinib treatment. Of the 18 afatinib dose reductions, 14 (78%), three (17%), and one (6%) resulted from diarrhea, paronychia, and stomatitis, respectively; no patients required a dose reduction because of rash. When minocycline treatment started, 21 patients (84%) had a rash of grade 1 or less, and three patients had a grade 2 rash. A response to afatinib was observed in 18 patients (72%) and the median duration of afatinib administration was 501 days. An adverse event related to minocycline (grade 1 nausea) was observed in one patient. A large proportion of the study patients started minocycline before grade 2 rash development and the severity of afatinib-related rash was lower than that previously reported. Oral TCs may be beneficial, especially if started early. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats: Brain Iron Quantification With Magnetic Resonance Imaging.

PubMed

Cao, Shenglong; Hua, Ya; Keep, Richard F; Chaudhary, Neeraj; Xi, Guohua

2018-04-01

Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined. Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points. ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits ( P <0.05). Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats. © 2018 American Heart Association, Inc.

Minocycline attenuates interferon-α-induced impairments in rat fear extinction.

PubMed

Bi, Qiang; Shi, Lijuan; Yang, Pingting; Wang, Jianing; Qin, Ling

2016-06-30

Extinction of conditioned fear is an important brain function for animals to adapt to a new environment. Accumulating evidence suggests that innate immune cytokines are involved in the pathology of psychotic disorders. However, the involvement of cytokines in fear dysregulation remains less investigated. In the present study, we investigated how interferon (IFN)-α disrupts the extinction of conditioned fear and propose an approach to rescue IFN-α-induced neurologic impairment. We used a rat model of auditory fear conditioning to study the effect of IFN-α on the fear memory process. IFN-α was infused directly into the amygdala of rats and examined the rats' behavioral response (freezing) to fear-conditioned stimuli. Immunohistochemical staining was used to examine the glia activity status of glia in the amygdala. The levels of the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the amygdala were measured by enzyme-linked immunosorbent assay. We also administrated minocycline, a microglial activation inhibitor, before the IFN-α infusion to testify the possibility to reverse the IFN-α-induced effects. Infusing the amygdala with IFN-α impaired the extinction of conditioned fear in rats and activated microglia and astrocytes in the amygdala. Administering minocycline prevented IFN-α from impairing fear extinction. The immunohistochemical and biochemical results show that minocycline inhibited IFN-α-induced microglial activation and reduced IL-1β and TNF-α production. Our findings suggest that IFN-α disrupts the extinction of auditory fear by activating glia in the amygdala and provides direction for clinical studies of novel treatments to modulate the innate immune system in patients with psychotic disorders.

Hippocampal Neuroprotection by Minocycline and Epigallo-Catechin-3-Gallate Against Cardiopulmonary Bypass-Associated Injury.

PubMed

Salameh, Aida; Einenkel, Anne; Kühne, Lydia; Grassl, Maria; von Salisch, Sandy; Kiefer, Phillip; Vollroth, Marcel; Dähnert, Ingo; Dhein, Stefan

2015-11-01

Surgical correction of congenital cardiac malformations mostly implies the use of cardiopulmonary bypass (CPB). However, a possible negative impact of CPB on cerebral structures like the hippocampus cannot be neglected. Therefore, we investigated the effect of CPB on hippocampus CA1 and CA3 regions without or with the addition of epigallocatechin-3-gallate (EGCG) or minocycline. We studied 42 piglets and divided them into six experimental groups: control without or with EGCG or minocycline, CPB without or with EGCG or minocycline. The piglets underwent 90 minutes CPB and subsequently, a 120-minute recovery and reperfusion phase. Thereafter, histology of the hippocampus was performed and the adenosine triphosphate (ATP) content was measured. Histologic evaluation revealed that CPB produced a significant peri-cellular edema in both CA regions. Moreover, we found an increased number of cells stained with markers for hypoxia, apoptosis and nitrosative stress. Most of these alterations were significantly reduced to or near to control levels by application of EGCG or minocycline. ATP content was significantly reduced within the hippocampus after CPB. This reduction could not be antagonized by EGCG or minocycline. In conclusion, CPB had a significant negative impact on the integrity of hippocampal neural cells. This cellular damage could be significantly attenuated by addition of EGCG or minocycline. © 2015 International Society of Neuropathology.

Translocation of iron from lysosomes to mitochondria during acetaminophen-induced hepatocellular injury: Protection by starch-desferal and minocycline.

PubMed

Hu, Jiangting; Kholmukhamedov, Andaleb; Lindsey, Christopher C; Beeson, Craig C; Jaeschke, Hartmut; Lemasters, John J

2016-08-01

, minocycline 1h after APAP decreased cell killing by half. In conclusion, release of Fe(2+) from lysosomes followed by uptake into mitochondria via MCFU occurs during APAP hepatotoxicity. Mitochondrial iron then catalyzes toxic hydroxyl radical formation, which triggers the MPT and cell killing. The efficacy of minocycline post-treatment shows minocycline as a possible therapeutic agent against APAP hepatotoxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

Minocycline modulates NFκB phosphorylation and enhances antimicrobial activity against Staphylococcus aureus in mesenchymal stromal/stem cells.

PubMed

Guerra, Alberto Daniel; Rose, Warren E; Hematti, Peiman; Kao, W John

2017-07-21

Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties due to their anti-inflammatory, angiogenic, and even antibacterial properties. We have shown previously that minocycline enhances the wound healing phenotype of MSCs, and MSCs encapsulated in poly(ethylene glycol) and gelatin-based hydrogels with minocycline have antibacterial properties against Staphylococcus aureus (SA). Here, we investigated the signaling pathway that minocycline modulates in MSCs which results in their enhanced wound healing phenotype and determined whether preconditioning MSCs with minocycline has an effect on antimicrobial activity. We further investigated the in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels in inoculated full-thickness cutaneous wounds. Modulation of cell signaling pathways in MSCs with minocycline was analyzed via western blot, immunofluorescence, and ELISA. Antimicrobial efficacy of MSCs pretreated with minocycline was determined by direct and transwell coculture with SA. MSC viability after SA coculture was determined via a LIVE/DEAD® stain. Internalization of SA by MSCs pretreated with minocycline was determined via confocal imaging. All protein and cytokine analysis was done via ELISA. The in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels was determined in Sprague-Dawley rats inoculated with SA. Two-way ANOVA for multiple comparisons was used with Bonferroni test assessment and an unpaired two-tailed Student's t test was used to determine p values for all assays with multiple or two conditions, respectively. Minocycline leads to the phosphorylation of transcriptional nuclear factor-κB (NFκB), but not c-Jun NH 2 -terminal kinase (JNK) or mitogen-activated protein kinase (ERK). Inhibition of NFκB activation prevented the minocycline-induced increase in VEGF secretion. Preconditioning of MSCs with minocycline led to a reduced production of the antimicrobial peptide LL-37, but enhanced antimicrobial

Minocycline attenuates colistin-induced neurotoxicity via suppression of apoptosis, mitochondrial dysfunction and oxidative stress.

PubMed

Dai, Chongshan; Ciccotosto, Giuseppe D; Cappai, Roberto; Wang, Yang; Tang, Shusheng; Xiao, Xilong; Velkov, Tony

2017-06-01

Neurotoxicity is an adverse effect patients experience during colistin therapy. The development of effective neuroprotective agents that can be co-administered during polymyxin therapy remains a priority area in antimicrobial chemotherapy. The present study investigates the neuroprotective effect of the synergistic tetracycline antibiotic minocycline against colistin-induced neurotoxicity. The impact of minocycline pretreatment on colistin-induced apoptosis, caspase activation, oxidative stress and mitochondrial dysfunction were investigated using cultured mouse neuroblastoma-2a (N2a) and primary cortical neuronal cells. Colistin-induced neurotoxicity in mouse N2a and primary cortical cells gives rise to the generation of reactive oxygen species (ROS) and subsequent cell death via apoptosis. Pretreatment of the neuronal cells with minocycline at 5, 10 and 20 μM for 2 h prior to colistin (200 μM) exposure (24 h), had an neuroprotective effect by significantly decreasing intracellular ROS production and by upregulating the activities of the anti-ROS enzymes superoxide dismutase and catalase. Minocycline pretreatment also protected the cells from colistin-induced mitochondrial dysfunction, caspase activation and subsequent apoptosis. Immunohistochemical imaging studies revealed colistin accumulates within the dendrite projections and cell body of primary cortical neuronal cells. To our knowledge, this is first study demonstrating the protective effect of minocycline on colistin-induced neurotoxicity by scavenging of ROS and suppression of apoptosis. Our study highlights that co-administration of minocycline kills two birds with one stone: in addition to its synergistic antimicrobial activity, minocycline could potentially ameliorate unwanted neurotoxicity in patients undergoing polymyxin therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions

Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis

PubMed Central

Sharma, Raman; Jayoussi, Ghaith Al; Tyrer, Hayley E.; Gamble, Joanne; Hayward, Laura; Guimaraes, Ana F.; Davies, Jill; Waterhouse, David; Cook, Darren A. N.; Myhill, Laura J.; Clare, Rachel H.; Cassidy, Andrew; Steven, Andrew; Johnston, Kelly L.; Ford, Louise; Turner, Joseph D.; Ward, Stephen A.; Taylor, Mark J.

2016-01-01

Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25–40 mg/Kg regimen is bioequivalent to a clinically effective 100–200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis. PMID:26996237

Evaluation of effect of minocycline on rewarding potential and alcohol relapse in place preference model in mice.

PubMed

Gajbhiye, Snehalata V; Tripathi, Raakhi K; Salve, Bharat; Petare, Anup; Potey, Anirudha V

2017-05-10

Medical management for alcohol abuse has limitations. Alcohol consumption activates N-methyl-d-aspartate receptors and release of nitric oxide which can be inhibited by minocycline as it readily crosses blood brain barrier and may have effect on alcohol consumption. Thus, study objective is to evaluate the effect of minocycline on rewarding property, extinction and the reinstatement phenomenon induced by alcohol in a model of conditioned place preference (CPP) in mice. To evaluate rewarding effects of alcohol, CPP procedure consisted of 4 parts, including adaptation (day 1), pre-conditioning test (day 2), conditionings with alcohol (days 3, 5, 7 and 9) or saline (days 4, 6, 8 and 10) and postconditioning test (day 11) conducted on 11 consecutive days. The groups included were saline treated group (alcohol control), naltrexone - 1mg/kg (positive control), and minocycline in the doses of 10, 30 and 50mg/kg. To evaluate the effect of minocycline on alcohol relapse, CPP procedure consisted 6 parts, the first 4 were the same as enumerated above followed by extinction (days 12-16) and reinstatement phase (day 17). The time spent in alcohol paired compartment by different groups, revealed that minocycline and naltrexone significantly attenuated alcohol-induced place preference compared to alcohol control (p<0.05). Pretreatment with minocycline and naltrexone blocked reinstatement of extinguished CPP. Minocycline may have a role in attenuating the rewarding property of alcohol and prevent alcohol relapse. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential role of licofelone, minocycline and their combination against chronic fatigue stress induced behavioral, biochemical and mitochondrial alterations in mice.

PubMed

Kumar, Anil; Vashist, Aditi; Kumar, Puneet; Kalonia, Harikesh; Mishra, Jitendriya

2012-01-01

Chronic fatigue stress (CFS) is a common complaint among general population. Persistent and debilitating fatigue severely impairs daily functioning and is usually accompanied by combination of several physical and psychiatric problems. It is now well established fact that oxidative stress and neuroinflammation are involved in the pathophysiology of chronic fatigue and related disorders. Targeting both COX (cyclooxygenase) and 5-LOX (lipoxygenase) pathways have been proposed to be involved in neuroprotective effect. In the present study, mice were put on the running wheel apparatus for 6 min test session daily for 21 days, what produced fatigue like condition. The locomotor activity and anxiety like behavior were measured on 0, 8(th), 15(th) and 22(nd) day. The brains were isolated on 22(nd) day immediately after the behavioral assessments for the estimation of oxidative stress parameters and mitochondrial enzyme complexes activity. Pre-treatment with licofelone (2.5, 5 and 10 mg/kg, po) and minocycline (50 and 100 mg/kg, po) for 21 days, significantly attenuated fatigue like behavior as compared to the control (rotating wheel activity test session, RWATS) group. Further, licofelone (5 and 10 mg/kg, po) and minocycline (50 and 100 mg/kg, po) drug treatments for 21 days significantly attenuated behavioral alterations, oxidative damage and restored mitochondrial enzyme complex activities (I, II, III and IV) as compared to control, whereas combination of licofelone (5 mg/kg) with minocycline (50 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect per se. The present study highlights the therapeutic potential of licofelone, minocycline and their combination against CFS in mice.

Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain.

PubMed

Li, Zhilin; Wei, Hong; Piirainen, Sami; Chen, Zuyue; Kalso, Eija; Pertovaara, Antti; Tian, Li

2016-11-01

Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII + spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα) + microglia/macrophages were found in the PFC of SNI rats. Interestingly in naïve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII + /CD172a + ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII + microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at the chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of Vancomycin-Resistant Enterococcal Infections in the Immunocompromised Host: Quinupristin-Dalfopristin in Combination with Minocycline

PubMed Central

Raad, Issam; Hachem, Ray; Hanna, Hend; Girgawy, Essam; Rolston, Kenneth; Whimbey, Estella; Husni, Rola; Bodey, Gerald

2001-01-01

Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D–MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia. PMID:11600379

Easy-Assessment of Levofloxacin and Minocycline in Relevant Biomimetic Media by HPLC-UV Analysis.

PubMed

Matos, Ana C; Pinto, Rosana V; Bettencourt, Ana F

2017-08-01

Simple, economic and environmental friendly high-performance liquid chromatography methods for levofloxacin and minocycline quantification in biomimetic media were developed and validate including their stability at body temperature, an often neglected evaluation parameter. Both methods are similar only differing in the wavelength setting, i.e., for levofloxacin and minocycline quantification the UV detection was set at 284 and at 273 nm, respectively. The separation of both antibiotics was achieved using a reversed-phase column and a mobile phase consisting of acetonitrile and water (15:85) with 0.6% triethylamine, adjusted to pH 3. As an internal standard for levofloxacin quantification, minocycline was used and vice versa. The calibration curves for both methods were linear (r = 0.99) over a concentration range of 0.3-16 μg/mL and 0.5-16 μg/mL for levofloxacin and minocycline, respectively, with precision, accuracy and recovery in agreement with international guidelines requirement. Levofloxacin revealed stability in all media and conditions, including at 37°C, with exception to freeze-thaw cycle conditions. Minocycline presented a more accentuated degradation profile over prolonged time courses, when compared to levofloxacin. Reported data is of utmost interest for pharma and biomaterials fields regarding the research and development of new local drug-delivery-systems containing either of these two antibiotics, namely when monitoring the in vitro release studies of those systems. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Minocycline, a putative neuroprotectant, co-administered with doxorubicin-cyclophosphamide chemotherapy in a xenograft model of triple-negative breast cancer

PubMed Central

Himmel, Lauren E.; Lustberg, Maryam B.; DeVries, A. Courtney; Poi, Ming; Chen, Ching-Shih; Kulp, Samuel K.

2016-01-01

Minocycline is purported to have neuroprotective properties in experimental models of some human neurologic diseases, and has therefore been identified as a putative neuroprotectant for chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. However, because its mechanism of action is believed to be mediated through anti-inflammatory, anti-apoptotic, and anti-oxidant pathways, co-administration of minocycline with chemotherapeutic agents has the potential to reduce the efficacy of anticancer drugs. The objective of this study is to evaluate the effect of minocycline on the activity of the AC chemotherapeutic regimen (Adriamycin [doxorubicin], Cytoxan [cyclophosphamide]) in in vitro and in vivo models of triple-negative breast cancer (TNBC). Clonogenic and methylthiazol tetrazolium (MTT) assays were used to assess survival and viability in two TNBC cell lines treated with increasing concentrations of AC in the presence or absence of minocycline. Biomarkers of apoptosis, cell stress, and DNA damage were evaluated by western blot. The in vivo effects of AC and minocycline, each alone and in combination, were assessed in a xenograft model of TNBC in female athymic nude mice by weekly tumor volume measurement, body and organ weight measurement, and histopathology. Apoptosis and proliferation were characterized by immunohistochemistry in the xenografts tumors. Brains from tumor-bearing mice were evaluated for microglial activation, glial scars, and the proportion of neural progenitor cells. Data from these in vitro and in vivo studies demonstrate that minocycline does not diminish the cytotoxic and tumor-suppressive effects of this chemotherapeutic drug combination in TNBC cells. Moreover, minocycline appeared to prevent the reduction in doublecortin-positive neural progenitor cells observed in AC-treated mice. We posit that minocycline may be useful clinically for its reported neuroprotective activity in breast cancer patients receiving AC without

Minocycline, a putative neuroprotectant, co-administered with doxorubicin-cyclophosphamide chemotherapy in a xenograft model of triple-negative breast cancer.

PubMed

Himmel, Lauren E; Lustberg, Maryam B; DeVries, A Courtney; Poi, Ming; Chen, Ching-Shih; Kulp, Samuel K

2016-10-01

Minocycline is purported to have neuroprotective properties in experimental models of some human neurologic diseases, and has therefore been identified as a putative neuroprotectant for chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. However, because its mechanism of action is believed to be mediated through anti-inflammatory, anti-apoptotic, and anti-oxidant pathways, co-administration of minocycline with chemotherapeutic agents has the potential to reduce the efficacy of anticancer drugs. The objective of this study is to evaluate the effect of minocycline on the activity of the AC chemotherapeutic regimen (Adriamycin [doxorubicin], Cytoxan [cyclophosphamide]) in in vitro and in vivo models of triple-negative breast cancer (TNBC). Clonogenic and methylthiazol tetrazolium (MTT) assays were used to assess survival and viability in two TNBC cell lines treated with increasing concentrations of AC in the presence or absence of minocycline. Biomarkers of apoptosis, cell stress, and DNA damage were evaluated by western blot. The in vivo effects of AC and minocycline, each alone and in combination, were assessed in a xenograft model of TNBC in female athymic nude mice by weekly tumor volume measurement, body and organ weight measurement, and histopathology. Apoptosis and proliferation were characterized by immunohistochemistry in the xenografts tumors. Brains from tumor-bearing mice were evaluated for microglial activation, glial scars, and the proportion of neural progenitor cells. Data from these in vitro and in vivo studies demonstrate that minocycline does not diminish the cytotoxic and tumor-suppressive effects of this chemotherapeutic drug combination in TNBC cells. Moreover, minocycline appeared to prevent the reduction in doublecortin-positive neural progenitor cells observed in AC-treated mice. We posit that minocycline may be useful clinically for its reported neuroprotective activity in breast cancer patients receiving AC without

Surface functionalization of TiO2 nanotubes with minocycline and its in vitro biological effects on Schwann cells.

PubMed

A, Lan; Xu, Wenzhou; Zhao, Jinghui; Li, Chunyan; Qi, Manlin; Li, Xue; Wang, Lin; Zhou, Yanmin

2018-06-20

Minocycline has been widely used in central nervous system disease. However, the effect of minocycline on the repairing of nerve fibers around dental implants had not been previously investigated. The aim of the present study was to evaluate the possibility of using minocycline for the repairing of nerve fibers around dental implants by investigating the effect of minocycline on the proliferation of Schwann cells and secretion of neurotrophic factors nerve growth factor and glial cell line-derived neurotrophic factor in vitro. TiO 2 nanotubes were fabricated on the surface of pure titanium via anodization at the voltage of 20, 30, 40 and 50 V. The nanotubes structure were characterized by scanning electron microscopy and examined with an optical contact angle. Then drug loading capability and release behavior were detected in vitro. The TiO 2 nanotubes loaded with different concentration of minocycline were used to produce conditioned media with which to treat the Schwann cells. A cell counting kit-8 assay and cell viability were both selected to study the proliferative effect of the specimens on Schwann cell. Reverse transcription-quantitative PCR and western blot analyses were used to detect the related gene/protein expression of Schwann cells. The results showed that the diameter of TiO 2 nanotubes at different voltage varied from 100 to 200 nm. The results of optical contact angle and releasing profile showed the nanotubes fabricated at the voltage of 30 V met the needs of the carrier of minocycline. In addition, the TiO 2 nanotubes loaded with the concentration of 20 μg/mL minocycline increased Schwann cells proliferation and secretion of neurotrophic factors in vitro. The results suggested that the surface functionalization of TiO 2 nanotubes with minocycline was a promising candidate biomaterial for the peripheral nerve regeneration around dental implants and has potential to be applied in improving the osseoperception of dental implant.

Microglia Activation and Schizophrenia: Lessons From the Effects of Minocycline on Postnatal Neurogenesis, Neuronal Survival and Synaptic Pruning.

PubMed

Inta, Dragos; Lang, Undine E; Borgwardt, Stefan; Meyer-Lindenberg, Andreas; Gass, Peter

2017-05-01

The implication of neuroinflammation in schizophrenia, sustained by recent genetic evidence, represents one of the most exciting topics in schizophrenia research. Drugs which inhibit microglia activation, especially the classical tetracycline antibiotic minocycline are currently under investigation as alternative antipsychotics. However, recent studies demonstrated that microglia activation is not only a hallmark of neuroinflammation, but plays important roles during brain development. Inhibition of microglia activation by minocycline was shown to induce extensive neuronal cell death and to impair subventricular zone (SVZ) neurogenesis and synaptic pruning in the early postnatal and adolescent rodent brain, respectively. These deleterious effects contrast with the neuroprotective actions of minocycline at adult stages. They are of potential importance for schizophrenia, since minocycline triggers similar pro-apoptotic effects in the developing brain as NMDA receptor (NMDAR) antagonists, known to induce long-term schizophrenia-like abnormalities. Moreover, altered postnatal neurogenesis, recently described in the human striatum, was proposed to induce striatal dopamine dysregulation associated with schizophrenia. Finally, the effect of minocycline on synapse remodeling is of interest considering the recently reported strong genetic association of the pruning-regulating complement factor gene C4A with schizophrenia. This raises the exciting possibility that in conditions of hyperactive synaptic pruning, as supposed in schizophrenia, the inhibitory action of minocycline turns into a beneficial effect, with relevance for early therapeutic interventions. Altogether, these data support a differential view on microglia activation and its inhibition. Further studies are needed to clarify the relevance of these results for the pathogenesis of schizophrenia and the use of minocycline as antipsychotic drug. © The Author 2016. Published by Oxford University Press on behalf of

Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis

PubMed Central

Jackson, Joseph W.; Singh, Meera V.; Singh, Vir B.; Jones, Letitia D.; Davidson, Gregory A.; Ture, Sara; Morrell, Craig N.; Schifitto, Giovanni; Maggirwar, Sanjay B.

2016-01-01

Platelets play an essential role in hemostasis and wound healing by facilitating thrombus formation at sites of injury. Platelets also mediate inflammation and contain several pro-inflammatory molecules including cytokines and chemokines that mediate leukocyte recruitment and activation. Not surprisingly, platelet dysfunction is known to contribute to several inflammatory disorders. Antiplatelet therapies, such as aspirin, adenosine diphosphate (ADP) antagonists, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and anticoagulants such as warfarin, dampen platelet activity at the risk of unwarranted bleeding. Thus, the development of drugs that reduce platelet-mediated inflammation without interfering with thrombus formation is of importance to combat platelet-associated disorders. We have shown here for the first time that the tetracycline antibiotic, minocycline, administered to HIV-infected individuals reduces plasma levels of soluble CD40L and platelet factor 4 levels, host molecules predominately released by platelets. Minocycline reduced the activation of isolated platelets in the presence of the potent platelet activator, thrombin, as measured by ELISA and flow cytometry. Platelet degranulation was reduced upon exposure to minocycline as shown by mepacrine retention and flow cytometry. However, minocycline had no effect on spreading, aggregation, GPIIb/IIIa activation, or in vivo thrombus formation. Lastly, immunoblot analysis suggests that the antiplatelet activity of minocycline is likely mediated by inhibition of mixed lineage kinase 3 (MLK3)-p38 MAPK signaling axis and loss of p38 activity. Our findings provide a better understanding of platelet biology and a novel repurposing of an established antibiotic, minocycline, to specifically reduce platelet granule release without affecting thrombosis, which may yield insights in generating novel, specific antiplatelet therapies. PMID:27270236

Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis.

PubMed

Jackson, Joseph W; Singh, Meera V; Singh, Vir B; Jones, Letitia D; Davidson, Gregory A; Ture, Sara; Morrell, Craig N; Schifitto, Giovanni; Maggirwar, Sanjay B

2016-01-01

Platelets play an essential role in hemostasis and wound healing by facilitating thrombus formation at sites of injury. Platelets also mediate inflammation and contain several pro-inflammatory molecules including cytokines and chemokines that mediate leukocyte recruitment and activation. Not surprisingly, platelet dysfunction is known to contribute to several inflammatory disorders. Antiplatelet therapies, such as aspirin, adenosine diphosphate (ADP) antagonists, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and anticoagulants such as warfarin, dampen platelet activity at the risk of unwarranted bleeding. Thus, the development of drugs that reduce platelet-mediated inflammation without interfering with thrombus formation is of importance to combat platelet-associated disorders. We have shown here for the first time that the tetracycline antibiotic, minocycline, administered to HIV-infected individuals reduces plasma levels of soluble CD40L and platelet factor 4 levels, host molecules predominately released by platelets. Minocycline reduced the activation of isolated platelets in the presence of the potent platelet activator, thrombin, as measured by ELISA and flow cytometry. Platelet degranulation was reduced upon exposure to minocycline as shown by mepacrine retention and flow cytometry. However, minocycline had no effect on spreading, aggregation, GPIIb/IIIa activation, or in vivo thrombus formation. Lastly, immunoblot analysis suggests that the antiplatelet activity of minocycline is likely mediated by inhibition of mixed lineage kinase 3 (MLK3)-p38 MAPK signaling axis and loss of p38 activity. Our findings provide a better understanding of platelet biology and a novel repurposing of an established antibiotic, minocycline, to specifically reduce platelet granule release without affecting thrombosis, which may yield insights in generating novel, specific antiplatelet therapies.

Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection

PubMed Central

Quick, Eamon D.; Seitz, Scott; Tyler, Kenneth L.

2017-01-01

ABSTRACT West Nile virus (WNV) is a neurotropic flavivirus that can cause significant neurological disease. Mouse models of WNV infection demonstrate that a proinflammatory environment is induced within the central nervous system (CNS) after WNV infection, leading to entry of activated peripheral immune cells. We utilized ex vivo spinal cord slice cultures (SCSC) to demonstrate that anti-inflammatory mechanisms may also play a role in WNV-induced pathology and/or recovery. Microglia are a type of macrophage that function as resident CNS immune cells. Similar to mouse models, infection of SCSC with WNV induces the upregulation of proinflammatory genes and proteins that are associated with microglial activation, including the microglial activation marker Iba1 and CC motif chemokines CCL2, CCL3, and CCL5. This suggests that microglia assume a proinflammatory phenotype in response to WNV infection similar to the proinflammatory (M1) activation that can be displayed by other macrophages. We now show that the WNV-induced expression of these and other proinflammatory genes was significantly decreased in the presence of minocycline, which has antineuroinflammatory properties, including the ability to inhibit proinflammatory microglial responses. Minocycline also caused a significant increase in the expression of anti-inflammatory genes associated with alternative anti-inflammatory (M2) macrophage activation, including interleukin 4 (IL-4), IL-13, and FIZZ1. Minocycline-dependent alterations to M1/M2 gene expression were associated with a significant increase in survival of neurons, microglia, and astrocytes in WNV-infected slices and markedly decreased levels of inducible nitric oxide synthase (iNOS). These results demonstrate that an anti-inflammatory environment induced by minocycline reduces viral cytotoxicity during WNV infection in ex vivo CNS tissue. IMPORTANCE West Nile virus (WNV) causes substantial morbidity and mortality, with no specific therapeutic treatments

Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats.

PubMed

Dai, Shuhui; Hua, Ya; Keep, Richard F; Novakovic, Nemanja; Fei, Zhou; Xi, Guohua

2018-06-05

Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2 ⁎ -weighted and T2 ⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

The Effects of Pregabalin and the Glial Attenuator Minocycline on the Response to Intradermal Capsaicin in Patients with Unilateral Sciatica

PubMed Central

Sumracki, Nicole M.; Hutchinson, Mark R.; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond B.; Rolan, Paul

2012-01-01

Background Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. Aim This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg. Methods/Results Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (−38% in affected leg, 95% CI for difference −19% to −52%). Both hand dominance and sex were significant covariates of response to capsaicin. Conclusions It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may

On the prescribing of oral doxycycline or minocycline by UK optometrists as part of management of chronic Meibomian Gland Dysfunction (MGD).

PubMed

Doughty, Michael J

2016-02-01

To review the special pharmacology of tetracycline antibiotics as anti-inflammatory drugs for treatment of obstructive Meibomian gland disease (MGD) METHODS: PubMed was used as principal resource for articles, regardless of language, on doxycycline and minocycline with key interests being on their serum and tissue pharmacokinetics and their use in clinical studies as part of management of MGD. With oral dosing of between 50 and 200mg, peak blood levels of these antibiotics have been reported to be predictably dose-dependent at between 1 and 5 microgram/mL, with human tear film levels not being detectable with 100mg dosing of doxycycline but levels of 0.2 microgram/mL with 200mg minocycline. That these two tetracycline antibiotics reach the conjunctiva is indicated by conjunctival pigmentary changes due to photosensitization after very long term use. Based the reported use in a range of clinical studies on MGD, dosing with these two antibiotics for MGD is likely to be useful at relatively low doses (e.g. 100mg for doxycycline or 50mg for minocycline, either at once or twice daily depending on severity at presentation and previous history) continued for 2 to 3 months, with the expected outcome being small-to-substantial decreases in abnormal appearance of the glands (from -4 to -89%) and increases in tear film stability (from 21 to 273%). Oral doxycycline and minocycline have predictable pharmacokinetics and have been reported to improve Meibomian gland dysfunction over a few months of use. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Effect of Minocycline on the Durability of Dentin Bonding Produced with Etch-and-Rinse Adhesives.

PubMed

Loguercio, A D; Stanislawczuk, R; Malaquias, P; Gutierrez, M F; Bauer, J; Reis, A

2016-01-01

To evaluate the effect of minocycline and chlorhexidine pretreatment of acid-etched dentin on the longevity of resin-dentin bond strength (μTBS) and nanoleakage of two-step etch-and-rinse adhesives. Before application of Prime & Bond NT and Adper Single Bond 2 in occlusal dentin, the dentin surfaces were treated with 37% phosphoric acid, rinsed, air-dried, and rewetted with water (control group), 2% minocycline, or 2% chlorexidine digluconate. Composite buildups were constructed incrementally, and specimens were longitudinally sectioned to obtain bonded sticks (0.8 mm 2 ) to be tested in tension (0.5 mm/min) immediately or after 24 months of water storage. For nanoleakage, two specimens of each tooth/period were immersed in the silver nitrate solution, photo-developed, and polished with SiC paper for analysis under energy-dispersive X-ray spectroscopy/scanning electron microscopy. Reductions of the μTBS and increases in the nanoleakage were observed for both adhesives when the rewetting procedure was performed with water. Stable bonds were observed for the 2% minocycline and 2% chlorexidine digluconate groups after 24 months. The use of 2% minocycline as pretreatment of acid-etched dentin is one alternative to retard the degradation of resin-dentin interfaces over a 24-month period as well as 2% chlorexidine digluconate.

[Two cases of skin pigmentation in association with minocycline therapy (author's transl)].

PubMed

Leroy, J P; Dorval, J C; Dewitte, J D; Guillerm, D; Volant, A; Masse, R

1981-01-01

Report of two cases of skin pigmentation during minocycline therapy. Examination showed confluent blue-gray oval patches on the anterior part of the legs, occurring after ingestion of respectively 12 g and 100 g of minocycline. Microscopic examination of each case was identical and showed two lesions: increase in the amount of melanine deposition in the basal layer of the epidermis; presence of brown-black pigment at all the level of the dermis but specially near the sweet glands. This pigment was strongly positive with Perls' stain. Electron microscopic examination showed a finely granular pigment exclusively intracellular in dermis fibroblast and macrophage. This pigment seemed to contain mainly hemodiderine.

Minocycline Promotes Neurite Outgrowth of PC12 Cells Exposed to Oxygen-Glucose Deprivation and Reoxygenation Through Regulation of MLCP/MLC Signaling Pathways.

PubMed

Tao, Tao; Feng, Jin-Zhou; Xu, Guang-Hui; Fu, Jie; Li, Xiao-Gang; Qin, Xin-Yue

2017-04-01

Minocycline, a semi-synthetic second-generation derivative of tetracycline, has been reported to exert neuroprotective effects both in animal models and in clinic trials of neurological diseases. In the present study, we first investigated the protective effects of minocycline on oxygen-glucose deprivation and reoxygenation-induced impairment of neurite outgrowth and its potential mechanism in the neuronal cell line, PC12 cells. We found that minocycline significantly increased cell viability, promoted neurite outgrowth and enhanced the expression of growth-associated protein-43 (GAP-43) in PC12 cells exposed to oxygen-glucose deprivation/reoxygenation injury. In addition, immunoblots revealed that minocycline reversed the overexpression of phosphorylated myosin light chain (MLC) and the suppression of activated extracellular signal-regulated kinase 1/2 (ERK1/2) caused by oxygen-glucose deprivation/reoxygenation injury. Moreover, the minocycline-induced neurite outgrowth was significantly blocked by Calyculin A (1 nM), an inhibitor of myosin light chain phosphatase (MLCP), but not by an ERK1/2 inhibitor (U0126; 10 μM). These findings suggested that minocycline activated the MLCP/MLC signaling pathway in PC12 cells after oxygen-glucose deprivation/reoxygenation injury, which resulted in the promotion of neurite outgrowth.

Attenuation of Pathogenic Immune Responses during Infection with Human and Simian Immunodeficiency Virus (HIV/SIV) by the Tetracycline Derivative Minocycline

PubMed Central

Drewes, Julia L.; Szeto, Gregory L.; Engle, Elizabeth L.; Liao, Zhaohao; Shearer, Gene M.; Zink, M. Christine; Graham, David R.

2014-01-01

HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo. PMID:24732038

Hydrophobic ion pairing of a minocycline/Ca(2+)/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release.

PubMed

Holmkvist, Alexander Dontsios; Friberg, Annika; Nilsson, Ulf J; Schouenborg, Jens

2016-02-29

Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca(2+) ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220 nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Calcium Binding-Mediated Sustained Release of Minocycline from Hydrophilic Multilayer Coatings Targeting Infection and Inflammation

PubMed Central

Zhang, Zhiling; Nix, Camilla A.; Ercan, Utku K.; Gerstenhaber, Jonathan A.; Joshi, Suresh G.; Zhong, Yinghui

2014-01-01

Infection and inflammation are common complications that seriously affect the functionality and longevity of implanted medical implants. Systemic administration of antibiotics and anti-inflammatory drugs often cannot achieve sufficient local concentration to be effective, and elicits serious side effects. Local delivery of therapeutics from drug-eluting coatings presents a promising solution. However, hydrophobic and thick coatings are commonly used to ensure sufficient drug loading and sustained release, which may limit tissue integration and tissue device communications. A calcium-mediated drug delivery mechanism was developed and characterized in this study. This novel mechanism allows controlled, sustained release of minocycline, an effective antibiotic and anti-inflammatory drug, from nanoscale thin hydrophilic polyelectrolyte multilayers for over 35 days at physiologically relevant concentrations. pH-responsive minocycline release was observed as the chelation between minocycline and Ca2+ is less stable at acidic pH, enabling ‘smart’ drug delivery in response to infection and/or inflammation-induced tissue acidosis. The release kinetics of minocycline can be controlled by varying initial loading, Ca2+ concentration, and Ca2+ incorporation into different layers, enabling facile development of implant coatings with versatile release kinetics. This drug delivery platform can potentially be used for releasing any drug that has high Ca2+ binding affinity, enabling its use in a variety of biomedical applications. PMID:24409292

Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection.

PubMed

Quick, Eamon D; Seitz, Scott; Clarke, Penny; Tyler, Kenneth L

2017-11-15

West Nile virus (WNV) is a neurotropic flavivirus that can cause significant neurological disease. Mouse models of WNV infection demonstrate that a proinflammatory environment is induced within the central nervous system (CNS) after WNV infection, leading to entry of activated peripheral immune cells. We utilized ex vivo spinal cord slice cultures (SCSC) to demonstrate that anti-inflammatory mechanisms may also play a role in WNV-induced pathology and/or recovery. Microglia are a type of macrophage that function as resident CNS immune cells. Similar to mouse models, infection of SCSC with WNV induces the upregulation of proinflammatory genes and proteins that are associated with microglial activation, including the microglial activation marker Iba1 and CC motif chemokines CCL2, CCL3, and CCL5. This suggests that microglia assume a proinflammatory phenotype in response to WNV infection similar to the proinflammatory (M1) activation that can be displayed by other macrophages. We now show that the WNV-induced expression of these and other proinflammatory genes was significantly decreased in the presence of minocycline, which has antineuroinflammatory properties, including the ability to inhibit proinflammatory microglial responses. Minocycline also caused a significant increase in the expression of anti-inflammatory genes associated with alternative anti-inflammatory (M2) macrophage activation, including interleukin 4 (IL-4), IL-13, and FIZZ1. Minocycline-dependent alterations to M1/M2 gene expression were associated with a significant increase in survival of neurons, microglia, and astrocytes in WNV-infected slices and markedly decreased levels of inducible nitric oxide synthase (iNOS). These results demonstrate that an anti-inflammatory environment induced by minocycline reduces viral cytotoxicity during WNV infection in ex vivo CNS tissue. IMPORTANCE West Nile virus (WNV) causes substantial morbidity and mortality, with no specific therapeutic treatments available

Bone marrow mesenchymal stem cells combined with minocycline improve spinal cord injury in a rat model

PubMed Central

Chen, Dayong; Zeng, Wei; Fu, Yunfeng; Gao, Meng; Lv, Guohua

2015-01-01

The aims of this study were to assess that the effects of bone marrow mesenchymal stem cells (BMSCs) combination with minocycline improve spinal cord injury (SCI) in rat model. In the present study, the Wistar rats were randomly divided into five groups: control group, SCI group, BMSCs group, Minocycline group and BMSCs + minocycline group. Basso, Beattie and Bresnahan (BBB) test and MPO activity were used to assess the effect of combination therapy on locomotion and neutrophil infiltration. Inflammation factors, VEGF and BDNF expression, caspase-3 activation, phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions were estimated using commercial kits or western blot, respectively. BBB scores were significantly increased and MPO activity was significantly undermined by combination therapy. In addition, combination therapy significantly decreased inflammation factors in SCI rats. Results from western blot showed that combination therapy significantly up-regulated the protein of VEGF and BDNF expression and down-regulated the protein of phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions in SCI rats. Combination therapy stimulation also suppressed the caspase-3 activation in SCI rats. These results demonstrated that the effects of bone marrow mesenchymal stem cells combination with minocycline improve SCI in rat model. PMID:26722382

Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast)

PubMed Central

Hutchinson, Mark R.; Lewis, Susannah S.; Coats, Benjamen D.; Skyba, David A.; Crysdale, Nicole Y.; Berkelhammer, Debra L.; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M.; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.; Johnson, Kirk W.

2009-01-01

Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused 3-to-5-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, whilst improving analgesia. PMID:18938237

Minocycline Does Not Decrease Intensity of Neuropathic Pain Intensity, But Does Improve Its Affective Dimension.

PubMed

Sumitani, Masahiko; Ueda, Hiroshi; Hozumi, Jun; Inoue, Reo; Kogure, Takamichi; Yamada, Yoshitsugu; Kogure, Takamichi

2016-01-01

Recent understanding of the neuron-glia communication shed light on an important role of microglia to develop neuropathic pain The analgesic effect of minocycline on neuropathic pain is promising but it remains unclear in clinical settings. This study included 20 patients with neuropathic pain of varied etiologies. We administered 100 mg/day of minocycline for 1 week and then 200 mg/day for 3 weeks, as an open-label adjunct to conventional analgesics. An 11-point numerical rating scale. (NRS) and the short-form McGill Pain Questionnaire (SF-MPQ) were used to evaluate pain severity. The data were collected at baseline and after 4 weeks of therapy and analyzed using the Wilcoxon signed-rank test. All except two of the patients tolerated the full dose of minocycline. There was no significant improvement in the scoring of NRS (5.6 ± 1.2 at baseline vs. 5.3 ± 1.9 at 4 weeks; P =.60). The total score of the SF-MPQ decreased significantly (17.2 ± 7.4 vs. 13.9 ± 9.6; P =.02), particularly in the affective subscale (4.4 ± 2.7 vs. 3.3 ± 3.6; P =.007) but not so in the sensory subscale (12.8 ± 5.2 vs. 10.6 ± 6.2; P =.06). We conclude that minocycline failed to decrease pain intensity but succeeded in reducing the affective dimension associated with neuropathic pain.

Minocycline Effects on IL-6 Concentration in Macrophage and Microglial Cells in a Rat Model of Neuropathic Pain.

PubMed

Moini-Zanjani, Taraneh; Ostad, Seyed-Nasser; Labibi, Farzaneh; Ameli, Haleh; Mosaffa, Nariman; Sabetkasaei, Masoumeh

2016-11-01

Evidence indicates that neuropathic pain pathogenesis is not confined to changes in the activity of neuronal systems but involves interactions between neurons, inflammatory immune and immune-like glial cells. Substances released from immune cells during inflammation play an important role in development and maintenance of neuropathic pain. It has been found that minocycline suppresses the development of neuropathic pain. Here, we evaluated the analgesic effect of minocycline in a chronic constriction injury (CCI) model of neuropathic pain in rat and assessed IL-6 concentration from cultured macrophage and microglia cells. Male Wistar rat (n=6, 150-200 g) were divided into three different groups: 1) CCI+vehicle, 2) sham+vehicle, and 3) CCI+drug. Minocycline (10, 20, and 40 mg/kg) was injected one hour before surgery and continued daily to day 14 post ligation. Von Frey filaments and acetone, as pain behavioral tests, were used for mechanical allodynia and cold allodynia, respectively. Experiments were performed on day 0 (before surgery) and days 1, 3, 5, 7, 10, and 14 post -injury. At day 14, rats were killed and monocyte-derived macrophage from right ventricle and microglia from lumbar part of the spinal cord were isolated and cultured in RPMI and Leibovitz's media, respectively. IL-6 concentration was evaluated in cell culture supernatant after 24 h. Minocycline (10, 20, and 40 mg/kg) attenuated pain behavior, and a decrease in IL-6 concentration was observed in immune cells compared to CCI vehicle-treated animals. Minocycline reduced pain behavior and decreased IL-6 concentration in macrophage and microglial cells.

A Phase II, Randomized, Double-Blind Clinical Study Evaluating the Safety, Tolerability, and Efficacy of a Topical Minocycline Foam, FMX103, for the Treatment of Facial Papulopustular Rosacea.

PubMed

Mrowietz, Ulrich; Kedem, Tal Hetzroni; Keynan, Rita; Eini, Meir; Tamarkin, Dov; Rom, Dror; Shirvan, Mitchell

2018-06-01

Our objective was to demonstrate the safety, tolerability, and efficacy of a minocycline foam, FMX103, in the treatment of moderate-to-severe facial papulopustular rosacea. This was a phase II, randomized, double-blind, multicenter study. Healthy subjects aged ≥ 18 years with moderate-to-severe rosacea that had been diagnosed ≥ 6 months previously and with ≥ 12 inflammatory facial lesions were randomized (1:1:1) to receive once-daily 1.5% FMX103, 3% FMX103, or vehicle for 12 weeks. The primary endpoint was the absolute change in inflammatory lesion count at week 12. Other assessments included grade 2 or higher Investigator's Global Assessment (IGA) improvement, IGA "clear" or "almost clear" (IGA 0/1), clinical erythema, and safety/tolerability. Safety and efficacy were evaluated at weeks 2, 4, 8, and 12, with a safety follow-up at week 16. A total of 232 subjects were randomized; 213 completed the study. At week 12, inflammatory lesion count reduction was significantly greater for the 1.5 and 3% FMX103 doses than for vehicle (21.1 and 19.1 vs. 7.8, respectively; both p < 0.001). Both doses were significantly better than vehicle for achieving grade 2 or higher IGA improvement and assessment of "clear" or "almost clear." Both doses appeared generally safe and well tolerated. In total, 11 (4.7%) subjects reported treatment-related treatment-emergent adverse events (TEAEs); all but one (eye discharge) were dermal related, and all resolved by study end. No treatment-related systemic TEAEs were reported. Four subjects discontinued the study because of TEAEs (3% FMX103, n = 3; vehicle, n = 1). Topical minocycline foam, FMX103, appeared to be an effective, safe, and well tolerated treatment for moderate-to-severe papulopustular rosacea. These results support further investigation in larger clinical trials. CLINICALTRIALS. NCT02601963.

Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kikuchi, Kiyoshi; Department of Neurosurgery, Omuta City General Hospital, 2-19-1 Takarazaka, Omuta-City, Fukuoka 836-8567; Kawahara, Ko-ichi

2009-07-24

High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death inmore » a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.« less

Validated stability-indicating densitometric thin-layer chromatography: application to stress degradation studies of minocycline.

PubMed

Jain, Nilu; Jain, Gaurav Kumar; Ahmad, Farhan Jalees; Khar, Roop Krishen

2007-09-19

A simple, stability-indicating high-performance thin-layer liquid chromatographic (HPTLC) method for analysis of minocycline was developed and validated. The densitometric analysis was carried out at 345 nm using methanol-acetonitrile-isopropyl alcohol-water (5:4:0.5:0.5, v/v/v/v) as mobile phase. The method employed TLC aluminium plates pre-coated with silica gel 60F-254 as the stationary phase. To achieve good result, plates were sprayed with a 10% (w/v) solution of disodium ethylene diaminetetraacetic acid (EDTA), the pH of which was adjusted to 9.0. Compact spots of minocycline were found at R(f) = 0.30+/-0.02. For proposed procedure, linearity (r = 0.9997), limit of detection (3.7 ng spot(-1)), recovery (99.23-100.16%), and precision (% R.S.D. < or = 0.364) was found to be satisfactory. The drug undergoes acidic and basic degradation, oxidation and photodegradation. All the peaks of degradation products were well resolved from the pure drug with significantly different R(f) values. The acidic and alkaline degradation kinetics of minocycline, evaluated using this method, is found to be of first order.

Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline.

PubMed

Chen, Wei; Zhao, Minjie; Zhao, Shuzhi; Lu, Qianyi; Ni, Lisha; Zou, Chen; Lu, Li; Xu, Xun; Guan, Huaijin; Zheng, Zhi; Qiu, Qinghua

2017-02-01

Chronic low-grade inflammation occurs in diabetic retinopathy (DR), but the underlying mechanism(s) remains (remain) unclear. NLRP3 inflammasome activation is involved in several other inflammatory diseases. Thus, we investigated the role of the NLRP3 inflammasome signaling pathway in the pathogenesis of DR. Diabetes was induced in rats by streptozotocin treatment for 8 weeks. They were treated with NLRP3 shRNA or minocycline during the last 4 weeks. High glucose-exposed human retinal microvascular endothelial cells (HRMECs) were co-incubated with antioxidants or subjected to TXNIP or NLRP3 shRNA interference. In high glucose-exposed HRMECs and retinas of diabetic rats, mRNA and protein expression of NLRP3, ASC, and proinflammatory cytokines were induced significantly by hyperglycemia. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were also observed with increased cell apoptosis and retinal vascular permeability, compared with the control group. NLRP3 silencing blocked these effects in the rat model and HRMECs, confirming that inflammasome activation contributed to inflammation in DR. TXNIP expression was increased by reactive oxygen species (ROS) overproduction in animal and cell models, whereas antioxidant addition or TXNIP silencing blocked IL-1β and IL-18 secretion in high glucose-exposed HRMECs, indicating that the ROS-TXNIP pathway mediates NLRP3 inflammasome activation. Minocycline significantly downregulated ROS generation and reduced TXNIP expression, subsequently inhibited NLRP3 activation, and further decreased inflammatory factors, which were associated with a decrease in retinal vascular permeability and cell apoptosis. Together, our data suggest that the TXNIP/NLRP3 pathway is a potential therapeutic target for the treatment of DR, and the use of minocycline specifically for such therapy may be a new avenue of investigation in inflammatory disease.

Minocycline Attenuates Depressive-Like Behaviour Induced by Rat Model of Testicular Torsion: Involvement of Nitric Oxide Pathway.

PubMed

Saravi, Seyed Soheil Saeedi; Mousavi, Seyyedeh Elaheh; Saravi, Seyed Sobhan Saeedi; Dehpour, Ahmad Reza

2016-04-01

Testicular torsion/detorsion (T/D) can induce depression in pre- and post-pubertal patients. This study was conducted to investigate the psychological impact of testicular torsion and mechanism underlying its depressive-like behaviour, as well as antidepressant-like activity of minocycline and possible involvement of nitric oxide (NO)/cyclic GMP pathway in this paradigm in male rats undergoing testicular T/D. Unilateral T/D was performed in 36 male adult Wistar rats, and different doses of minocycline were injected alone or combined with N(ω) -nitro-l-arginine methyl ester (l-NAME), non-specific NO synthase (NOS) inhibitor; aminoguanidine (AG), specific inducible NOS inhibitor; l-arginine, an NO precursor; and selective PDE5I, sildenafil. After assessment of locomotor activity in open-field test, immobility times were recorded in the forced swimming test (FST). Moreover, 30 days after testicular T/D, testicular venous testosterone and serum nitrite concentrations were measured. A correlation was observed between either a decrease in plasma testosterone or an increase in serum nitrite concentrations with prolongation in immobility time in the testicular T/D-operated rats FST. Minocycline (160 mg/kg) exerted the highest significant antidepressant-like effect in the operated rats in the FST (p < 0.001). Furthermore, combination of subeffective doses of minocycline (80 mg/kg) and either l-NAME (10 mg/kg) or AG (50 mg/kg) demonstrated a significant robust antidepressant-like activity in T/D group (p < 0.01). Consequently, NO/cGMP pathway was involved in testicular T/D-induced depressive-like behaviour and antidepressant-like activity of minocycline in the animal model. Moreover, a contribution was observed between either decreased testosterone or elevated serum nitrite levels and depressive-like behaviour following testicular T/D. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

On the effect of minocycline on the depressive-like behavior of mice repeatedly exposed to malathion: interaction between nitric oxide and cholinergic system.

PubMed

Saeedi Saravi, Seyed Soheil; Amirkhanloo, Roya; Arefidoust, Alireza; Yaftian, Rahele; Saeedi Saravi, Seyed Sobhan; Shokrzadeh, Mohammad; Dehpour, Ahmad Reza

2016-06-01

This study was performed to investigate the antidepressant-like effect of minocycline in mice exposed to organophosphate pesticide malathion and possible involvement of nitric oxide/cGMP pathway in this paradigm. Mice were administered specific doses of malathion once daily for 7 consecutive days. After induction of depression, different doses of minocycline were daily injected alone or combined with non-specific NOS inhibitor, L-NAME, specific inducible NOS inhibitor, AG, NO precursor, L-arginine, and PDE5I, sildenafil. After locomotion assessment in open-field test, immobility times were recorded in the FST and TST. Moreover, hippocampal nitrite concentrations and acetylcholinesterase activity were measured. The results showed that repeated exposure to malathion induces depressive-like behavior at dose of 250 mg/kg. Minocycline (160 mg/kg) significantly reduced immobility times in FST and TST (P < 0.001). Combination of sub-effective doses of minocycline (80 mg/kg) with either L-NAME (3 mg/kg) or AG (25 mg/kg) significantly exerted a robust antidepressant-like effect in FST and TST (P < 0.001). Furthermore, minocycline at the same dose which has antidepressant-like effect, significantly reduced hippocampal nitrite concentration. The investigation indicates the essential role for NO/cGMP pathway in malathion-induced depressive-like behavior and antidepressant-like effect of minocycline. Moreover, the interaction between nitrergic and cholinergic systems are suggested to be involved in malathion-induced depression.

Pretreatment with minocycline restores neurogenesis in the subventricular zone and subgranular zone of the hippocampus after ketamine exposure in neonatal rats.

PubMed

Lu, Yang; Giri, P K; Lei, Shan; Zheng, Juan; Li, Weisong; Wang, Ning; Chen, Xinlin; Lu, Haixia; Zuo, Zhiyi; Liu, Yong; Zhang, Pengbo

2017-06-03

Ketamine is commonly used for anesthesia in pediatric patients. Recent studies indicated that ketamine exposure in the developing brain can induce neuroapoptosis and disturb normal neurogenesis, which will result in long-lasting cognitive impairment. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative disease models. In the present study, we investigated whether the disturbed neurogenesis and behavioral deficits after ketamine neonatal exposure could be alleviated by minocycline. Postnatal day (PND)7 Sprague-Dawley rat pups randomly received either normal saline, ketamine, or minocycline 30min prior to ketamine administration, respectively. The rats were decapitated at PND14 for the detection of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampus by immunostaining. The protein expression of p-Akt, p-GSK-3β in the SVZ and SGZ at 12h after anesthesia, PND10 and PND14 were assessed by western blotting analysis. At PND 42-47, spatial learning and memory abilities were measured by the Morris water maze in all groups. Our data showed that ketamine exposure in neonatal rats resulted in neurogenetic damage and persistent cognitive deficits, and that pretreatment with minocycline eliminated the brain development damage and improved the behavioral function in adult rats. Moreover, the protection of minocycline is associated with the PI3K/Akt signaling pathway. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Acute treatment of migraine headaches.

PubMed

Taylor, Frederick R

2010-04-01

Optimum acute treatment of migraine requires prevention of headache as a top priority. Recognition of the multitude of migraine presentations, the frequency of total headache attacks, and number of days of headache disability are critical. Successful treatment requires excellent patient-clinician communication enhancing confidence and mutual trust based on patient needs and preferences. Optimum management of acute migraine nearly always requires pharmacologic treatment for rapid resolution. Migraine-specific triptans, dihydroergotamine, and several antiinflammatories have substantial empirical clinical efficacy. Older nonspecific drugs, particularly butalbital and opioids, contribute to medication overuse headache and are to be avoided. Clinicians should utilize evidence-based acute migraine-specific therapy stressing the imperative acute treatment goal of early intervention, but not too often with the correct drug, formulation, and dose. This therapy needs to provide cost-effective fast results, meaningful to the patient while minimizing the need for additional drugs. Migraine-ACT evaluates 2-hour pain freedom with return to normal function, comfort with treatment, and consistency of response. Employ a thoroughly educated patient, formulary, testimonials, stratification, and rational cotherapy against the race to central sensitization for optimum outcomes. Thieme Medical Publishers.

Phenotypic and genotypic characterization of tetracycline and minocycline resistance in Clostridium perfringens

USDA-ARS?s Scientific Manuscript database

The aim of this study was to determine the incidence of tetracycline resistance and the prevalence of tetracycline-resistance genes in strains of Clostridium perfringens isolated from different sources between 1994 and 2005. Susceptibility to tetracycline and minocycline in C. perfringens isolates ...

Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method.

PubMed

Kashi, Tahereh Sadat Jafarzadeh; Eskandarion, Solmaz; Esfandyari-Manesh, Mehdi; Marashi, Seyyed Mahmoud Amin; Samadi, Nasrin; Fatemi, Seyyed Mostafa; Atyabi, Fatemeh; Eshraghi, Saeed; Dinarvand, Rassoul

2012-01-01

Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. The nanoparticles prepared in this study were spherical, with an average particle size of 85-424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug.

Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

MedlinePlus

... Childhood ALL Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key ...

Treatment Options for Adult Acute Lymphoblastic Leukemia

MedlinePlus

... Childhood ALL Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key ...

Oligodendrocyte death, neuroinflammation, and the effects of minocycline in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION).

PubMed

Mehrabian, Zara; Guo, Yan; Weinreich, Daniel; Bernstein, Steven L

2017-01-01

Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its models is associated with neurodegenerative inflammation. Minocycline is a tetracycline derivative antibiotic believed to exert a neuroprotective effect by selective alteration and activation of the neuroinflammatory response. We evaluated minocycline's post-induction ability to modify early and late post-ischemic inflammatory responses and its retinal ganglion cell (RGC)-neuroprotective ability. We used the rodent NAION (rNAION) model in male Sprague-Dawley rats. Animals received either vehicle or minocycline (33 mg/kg) daily intraperitoneally for 28 days. Early (3 days) ON-cytokine responses were evaluated, and oligodendrocyte death was temporally evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. Cellular inflammation was evaluated with immunohistochemistry, and RGC preservation was compared with stereology of Brn3a-positive cells in flat mounted retinas. Post-rNAION, oligodendrocytes exhibit a delayed pattern of apoptosis extending over a month, with extrinsic monocyte infiltration occurring only in the primary rNAION lesion and progressive distal microglial activation. Post-induction minocycline failed to improve retinal ganglion cell survival compared with the vehicle treated (893.14 vs. 920.72; p>0.9). Cytokine analysis of the rNAION lesion 3 days post-induction revealed that minocycline exert general inflammatory suppression without selective upregulation of cytokines associated with the proposed alternative or neuroprotective M2 inflammatory pathway. The pattern of cytokine release, extended temporal window of oligodendrocyte death, and progressive microglial activation suggests that selective neuroimmunomodulation, rather than general inflammatory suppression, may be required for effective repair strategies in ischemic optic neuropathies.

Effects of Minocycline on Urine Albumin, Interleukin-6, and Osteoprotegerin in Patients with Diabetic Nephropathy: A Randomized Controlled Pilot Trial

PubMed Central

Wang, Ying; Tong, Lili; Pak, Youngju; Andalibi, Ali; LaPage, Janine A.; Adler, Sharon G.

2016-01-01

Background We tested minocycline as an anti-proteinuric adjunct to renin-angiotensin-aldosterone system inhibitors (RAASi) in diabetic nephropathy (DN) and measured urinary biomarkers to evaluate minocycline’s biological effects. Methods Design: Prospective, single center, randomized, placebo-controlled, intention-to-treat pilot trial. Inclusion. Type 2 diabetes/DN; Baseline creatinine clearance > 30 mL/min; proteinuria ≥ 1.0 g/day; Age ≥30 years; BP <150/95 mm Hg; intolerant of/at maximum RAASi dose. Protocol. 3-wk screening; Baseline randomization; Urine and blood measures at months 1, 2, 4, and Month 6 study completion. Urine interleukin-6 (IL-6) and osteoprotegerin were measured in a subset. Primary outcome. Natural log of urine protein/creatinine (ln U P:Cr) ratio at Month 6 vs Baseline. Results 30 patients completed the study. The 15% decline in U P: Cr in minocycline patients (6 month P:Cr ÷ Baseline P:Cr, 0.85 vs. 0.92) was not significant (p = 0.27). Creatinine clearance did not differ in the 2 groups. Urine IL-6:Cr (p = 0.03) and osteoprotegerin/Cr (p = 0.046) decrements were significant. Minocycline modified the relationship between urine IL-6 and proteinuria, suggesting a protective biological effect. Conclusions Although the decline in U P:Cr in minocycline patients was not statistically significant, the significant differences in urine IL-6 and osteoprotegerin suggest that minocycline may confer cytoprotection in patients with DN, providing a rationale for further study. Trial Registration Clinicaltrials.gov NCT01779089 PMID:27019421

Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration: Biochemical and Molecular Interventions.

PubMed

Kumar, Vinod; Singh, Brajesh Kumar; Chauhan, Amit Kumar; Singh, Deepali; Patel, Devendra Kumar; Singh, Chetna

2016-07-01

Accumulation of zinc (Zn) in dopaminergic neurons is implicated in Parkinson's disease (PD), and microglial activation plays a critical role in toxin-induced Parkinsonism. Oxidative stress is accused in Zn-induced dopaminergic neurodegeneration; however, its connection with microglial activation is still not known. This study was undertaken to elucidate the role and underlying mechanism of microglial activation in Zn-induced nigrostriatal dopaminergic neurodegeneration. Male Wistar rats were treated intraperitoneally with/without zinc sulphate (20 mg/kg) in the presence/absence of minocycline (30 mg/kg), a microglial activation inhibitor, for 2-12 weeks. While neurobehavioral and biochemical indexes of PD and number of dopaminergic neurons were reduced, the number of microglial cells was increased in the substantia nigra of the Zn-exposed animals. Similarly, Zn elevated lipid peroxidation (LPO) and activities of superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; however, catalase activity was reduced. Besides, Zn increased an association of NADPH oxidase subunit p67(phox) with membrane, cytochrome c release from the mitochondria and cleavage of pro-caspase 3. Zn attenuated the expression of tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT-2) while augmented the expression of dopamine transporter (DAT) and heme oxygenase-1 (HO-1). Minocycline alleviated Zn-induced behavioural impairments, loss of TH-positive neurons, activated microglial cells and biochemical indexes and modulated the expression of studied genes/proteins towards normalcy. The results demonstrate that minocycline reduces the number of activated microglial cells and oxidative stress, which rescue from Zn-induced changes in the expression of monoamine transporter and nigrostriatal dopaminergic neurodegeneration.

Minocycline enhances the mesenchymal stromal/stem cell pro-healing phenotype in triple antimicrobial-loaded hydrogels.

PubMed

Guerra, Alberto Daniel; Rose, Warren E; Hematti, Peiman; Kao, W John

2017-03-15

Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) crosslinked hydrogels have led to controlled cellular presentation at wound sites with favorable wound healing outcomes. However, the therapeutic potential of MSC-loaded hydrogels may be limited by non-specific protein adsorption on the delivery matrix that could facilitate the initial adhesion of microorganisms and subsequent virulent biofilm formation. Antimicrobials loaded concurrently in the hydrogels with MSCs could reduce microbial bioburden and promote healing, but the antimicrobial effect on the MSC wound healing capacity and the antibacterial efficacy of the hydrogels is unknown. We demonstrate that minocycline specifically induces a favorable change in MSC migration capacity, proliferation, gene expression, extracellular matrix (ECM) attachment, and adhesion molecule and growth factor release with subsequent increased angiogenesis. We then demonstrate that hydrogels loaded with MSCs, minocycline, vancomycin, and linezolid can significantly decrease bacterial bioburden. Our study suggests that minocycline can serve as a dual mechanism for the regenerative capacity of MSCs and the reduction of bioburden in triple antimicrobial-loaded hydrogels. Wound healing is a complex biological process that can be hindered by bacterial infection, excessive inflammation, and inadequate microvasculature. In this study, we develop a new formulation of poly(ethylene glycol) diacrylate and thiolated gelatin poly(ethylene glycol) crosslinked hydrogels loaded with minocycline, vancomycin, linezolid, and mesenchymal stromal/stem cells that induces a favorable wound healing phenotype in mesenchymal stromal/stem cells and prevents bacterial

Ultrastructural and x-ray microanalytical observations of minocycline-related hyperpigmentation of the skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, S.; Murphy, G.F.; Bernhard, J.D.

1981-09-01

In order to elucidate the nature and distribution of the pigment responsible for the circumscribed blue-black cutaneous hyperpigmentation occurring after administration of minocycline hydrochloride, transmission electron microscopy and energy-dispersive electron x-ray microanalysis were performed on lesional skin. Ultrastructural observations demonstrated electron-dense iron-containing particles either incorporated into a variety of siderosomes, within dermal histiocytes, free within the cytoplasm, or, rarely, scattered among dermal collagen fibers. Electron x-ray microanalysis confirmed iron content present within these particles. Although siderosomal inclusions contained occasional melanosome complexes, the degree of deposition of electron-dense iron-containing particles in dermal histiocytes seemed to be primarily responsible for the blue-blackmore » discoloration of the skin. The present study is an investigation of the structure and composition of the pigment responsible for minocycline-related cutaneous hyperpigmentation.« less

Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method

PubMed Central

Kashi, Tahereh Sadat Jafarzadeh; Eskandarion, Solmaz; Esfandyari-Manesh, Mehdi; Marashi, Seyyed Mahmoud Amin; Samadi, Nasrin; Fatemi, Seyyed Mostafa; Atyabi, Fatemeh; Eshraghi, Saeed; Dinarvand, Rassoul

2012-01-01

Background Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Methods Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. Results The nanoparticles prepared in this study were spherical, with an average particle size of 85–424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Conclusion Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug. PMID:22275837

Preventive effect of kampo medicine (hangeshashin-to, TJ-14) plus minocycline against afatinib-induced diarrhea and skin rash in patients with non-small cell lung cancer

PubMed Central

Ichiki, Masao; Wataya, Hiroshi; Yamada, Kazuhiko; Tsuruta, Nobuko; Takeoka, Hiroaki; Okayama, Yusuke; Sasaki, Jun; Hoshino, Tomoaki

2017-01-01

Purpose Diarrhea and oral mucositis induced by afatinib can cause devastating quality of life issues for patients undergoing afatinib treatment. Several studies have shown that hangeshashin-to (TJ-14) might be useful for chemotherapy-induced diarrhea and oral mucositis. In this study, we investigated the prophylactic effects of TJ-14 for afatinib-induced diarrhea and oral mucositis and minocycline for afatinib-induced skin rash. Patients and methods First- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have become the standard first-line treatment in patients with EGFR-mutated non-small cell lung cancer. The incidence of diarrhea was higher with afatinib than with gefitinib, and we conducted a single-arm Phase II study with afatinib. Patients who had previously undergone treatment with afatinib were ineligible. Both TJ-14 (7.5 g/day) and minocycline (100 mg/day) were administered simultaneously from the start of afatinib administration. The primary end point was the incidence of ≥ grade 3 (G3) diarrhea (increase of ≥7 stools/day over baseline) during the first 4 weeks of treatment. The secondary end points were the incidence of ≥ G3 oral mucositis (severe pain interfering with oral intake) and $ G3 skin toxicity (severe or medically significant but not immediately life-threatening). Results A total of 29 patients (nine men and 20 women; median age, 66 years; performance status, 0/1/2: 18/10/1) were enrolled from four centers. Four patients had undergone prior treatment with chemotherapy, including gefitinib or erlotinib. In all, 20 (68.9%) patients and one (3.4%) patient had diarrhea of any grade and ≥ G3, respectively. One (3.4%) patient had ≥ G3 oral mucositis; no patients had ≥ G3 skin rash. A total of 18 (62%) of the 29 patients achieved a partial response. Conclusion The present study indicated a trend in which TJ-14 reduced the risk of afatinib-induced diarrhea and minocycline reduced the risk of afatinib

Optical microscopy of targeted drug delivery and local distribution in skin of a topical minocycline: implications in translational research and guidance for therapeutic dose selection (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hermsmeier, Maiko; Sawant, Tanvee; Lac, Diana; Yamamoto, Akira; Chen, Xin; Huang, Susan Y.; Nagavarapu, Usha; Evans, Conor L.; Chan, Kin Foong; Daniels, AnnaMarie

2017-02-01

Acne vulgaris is a chronic inflammatory skin condition commonly resulting in negative aesthetic and social impacts on those affected. Minocycline, currently available as an oral antibiotic for moderate to severe acne, has a known minimum inhibitory concentration (MIC) for the acne-causing bacterium Propionibacterium acnes (P. acnes) in vitro, with its anti-inflammatory properties also eliciting inhibitory effects on pro-inflammatory molecules. A novel topical gel composition containing solubilized minocycline (BPX-01) has been developed to directly deliver the drug to the skin. Because minocycline is a known fluorophore, fluorescence microscopy and concurrent quantitative measurements were performed on excised human facial skin dosed with different concentrations, in order to determine the spatial distribution of the drug and quantification of its local concentration in the epidermis and the pilosebaceous unit where P. acnes generally reside. Local minocycline delivery confirmed achievement of an adequate therapeutic dose to support clinical studies. Subsequently, a 4-week double-blind, randomized, vehicle controlled clinical study was performed to assess the safety and efficacy of 1% minocycline BPX-01 applied daily. No instances of cutaneous toxicity were reported, and a greater than 1 log reduction of P. acnes count was observed at week 4 with statistical significance from baseline and vehicle control. In addition, no detectable amounts of minocycline in the plasma were reported, suggesting the potential of this new formulation to diminish the known systemic adverse effects associated with oral minocycline. Follow-on clinical plans are underway to further establish the safety of BPX-01 and to evaluate its efficacy against inflammatory acne lesions in a 225 patient multi-center dose-finding study.

Treatment of Acute Pelvic Inflammatory Disease

PubMed Central

Sweet, Richard L.

2011-01-01

Pelvic inflammatory disease (PID), one of the most common infections in nonpregnant women of reproductive age, remains an important public health problem. It is associated with major long-term sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, treatment of acute PID and its complications incurs substantial health care costs. Prevention of these long-term sequelae is dependent upon development of treatment strategies based on knowledge of the microbiologic etiology of acute PID. It is well accepted that acute PID is a polymicrobic infection. The sexually transmitted organisms, Neisseria gonorrhoeae and Chlamydia trachomatis, are present in many cases, and microorganisms comprising the endogenous vaginal and cervical flora are frequently associated with PID. This includes anaerobic and facultative bacteria, similar to those associated with bacterial vaginosis. Genital tract mycoplasmas, most importantly Mycoplasma genitalium, have recently also been implicated as a cause of acute PID. As a consequence, treatment regimens for acute PID should provide broad spectrum coverage that is effective against these microorganisms. PMID:22228985

Study on the treatment of acute thallium poisoning.

PubMed

Zhang, Hong-Tao; Qiao, Bao-Ping; Liu, Bao-Ping; Zhao, Xian-Guo

2014-05-01

Acute thallium poisoning rarely occurs but is a serious and even fatal medical condition. Currently, patients with acute thallium poisoning are usually treated with Prussian blue and blood purification therapy. However, there are few studies about these treatments for acute thallium poisoning. Nine patients with acute thallium poisoning from 1 family were treated successfully with Prussian blue and different types of blood purification therapies and analyzed. Prussian blue combined with sequential hemodialysis, hemoperfusion and/or continuous veno-venous hemofiltration were effective for the treatment of patients with acute thallium poisoning, even after delayed diagnosis. Blood purification therapies help in the clearance of thallium in those with acute thallium poisoning. Prussian blue treatment may do the benefit during this process.

Acute Treatment of Migraine

PubMed Central

ÖZTÜRK, Vesile

2013-01-01

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patient’s quality of life. Migraine has been described as a chronic disorder that characterized with attacks. Attacks are characterized by moderate–severe, often unilateral, pulsating headache attacks, typically lasting 4 to 72 hours. Migraine remains underdiagnosed and undertreated despite advances in the understanding of its pathophysiology. This article reviews management of migraine acute pharmacological treatment. Currently, for the acute treatment of migraine attacks, non-steroidal anti-inflammatory drugs (NSAIDs) and triptans (serotonin 5HT1B/1D receptor agonists) are recommended. Before intake of NSAID and triptans, metoclopramide or domperidone is useful. In very severe attacks, subcutaneous sumatriptan is first choice. The patient should be treated early in the attack, use an adequate dose and formulation of a medication. Ideally, acute therapy should be restricted to no more than 2 to 3 days per week to avoid medication overuse. PMID:28360580

Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2Rγnull mice

PubMed Central

Singh, Maneesh; Singh, Pratibha; Vaira, Dolores; Amand, Mathieu; Rahmouni, Souad; Moutschen, Michel

2014-01-01

More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2Rγnull mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV. PMID:24409837

Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun

Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs–Ringer–HEPES buffer at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca{sup 2+} uptake wasmore » measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca{sup 2+} uptake and suppressed the Ca{sup 2+}-induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca{sup 2+} uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. - Highlights: • Minocycline and doxycycline are the only cytoprotective tetracyclines of those tested • Cytoprotective tetracyclines inhibit the MPT and mitochondrial calcium and iron uptake. �

Liquid chromatographic determination of minocycline in brain-to-plasma distribution studies in the rat.

PubMed

Colovic, Milena; Caccia, Silvio

2003-07-05

An isocratic reversed-phase high-performance liquid chromatographic procedure was developed for the determination of minocycline in rat plasma and brain and applied to brain-to-blood (plasma) distribution studies. The procedure is based on isolation of the compound and the internal standard (either demeclocycline or tetracycline may be used) from plasma and brain constituents using the Oasis HLB cartridge, with satisfactory recovery and specificity, and separation on a Symmetry Shield RP8 (15 cm x 4.6 mm, 3.5 microm) column coupled with a UV detector set at 350 nm. The assay was linear over a wide range, with a lower limit of quantification of 50 ng ml(-1) or g(-1), using 0.2 ml of plasma and about 200 mg of brain tissue. Precision and accuracy were acceptable. In the rat minocycline crossed the blood-brain barrier slowly, achieving mean brain concentrations between 30 and 40% of the equivalent systemic exposure, regardless of the dose and route of administration.

Prophylactic Effect of Oral Minocycline in Combination with Topical Steroid and Skin Care Against Panitumumab-induced Acneiform Rash in Metastatic Colorectal Cancer Patients.

PubMed

Yamada, Maya; Iihara, Hirotoshi; Fujii, Hironori; Ishihara, Masashi; Matsuhashi, Nobuhisa; Takahashi, Takao; Yoshida, Kazuhiro; Itoh, Yoshinori

2015-11-01

Although the anti-EGFR monoclonal antibody panitumumab is effective in treating colorectal cancer, the occurrence of severe skin disorders often discontinues therapy. Herein, we investigated by a retrospective chart review the effect of prophylactic oral minocycline in combination with skin treatment using moisturizer on the incidence of skin disorders and tumor response in metastatic colorectal cancer patients who received panitumumab. In a total of 55 patients, 38 patients were eligible, consisting the pre-emptive group (N=25) and reactive group (N=13). Acneiform rash and other adverse events were graded according to the CTCAE v4.0. The occurrence of acneiform rash (grade ≥2) was significantly lower in pre-emptive group than in reactive group (44.0% vs. 84.6%, p=0.04). No significant differences in the occurrence of other adverse events were observed between the two groups. Tumor response was not significantly different between the two groups (36.0% vs. 7.7%, OR, 6.75; 95% confidence interval (CI)=0.75-60.76, p=0.12). Mean time to treatment failure was 149.7 days and 110.2 days in the pre-emptive group and reactive treatment group, respectively (HR=0.58; 95% CI= 0.26-1.28, p=0.18). Prophylactic oral minocycline combined with skin care reduced panitumumab-induced acneiform rash without a significant influence on tumor response. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Is there a role for rifampicin, ofloxacin and minocycline (ROM) therapy in the treatment of leprosy? Systematic review and meta-analysis.

PubMed

Setia, Maninder S; Shinde, Santosh S; Jerajani, Hemangi R; Boivin, Jean-François

2011-12-01

A combination of rifampicin, ofloxacin and minocycline (ROM) is one of the newer recommendations for treatment of leprosy. We performed a systematic review and a meta-analysis of studies that had evaluated the efficacy of ROM therapy in treatment of paucibacillary and multibacillary leprosy patients. Studies were identified by searching the PubMed, Embase, LILACS and Cochrane databases. Data were abstracted from all relevant studies, and fixed effects models were used to calculate the summary estimate of effect in paucibacillary and multibacillary leprosy patients. Six studies comparing ROM therapy to multidrug therapy and eight studies that evaluated the effect of ROM therapy alone (no comparison group) were included in the review and meta-analysis. The combined estimate for single dose ROM vs. multidrug therapy in paucibacillary leprosy patients suggested that ROM was less effective than multidrug therapy in these patients [relative risk: 0.91, 95% confidence intervals (CI): 0.86-0.97]. However, the combined estimate for multiple doses of ROM vs. multidrug therapy in multibacillary leprosy patients suggested that ROM was as effective as multidrug therapy in reducing bacillary indices in these patients (proportion change: -4%, 95% CI -31% to 23%). No major side effects were reported in either the ROM or the multidrug treatment groups. Single-dose ROM therapy was less effective than multidrug therapy in paucibacillary patients. However, there are insufficient data to come to a valid conclusion on the efficacy of multidose ROM therapy in multibacillary leprosy, and additional studies with ROM therapy in multibacillary leprosy are needed. Furthermore, multiple doses may be considered as another alternative even for paucibacillary patients, and randomised controlled trials of this therapy may be useful to understand its contribution in the treatment and control of leprosy. © 2011 Blackwell Publishing Ltd.

The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can be downregulated by minocycline: possible implications for long-term treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis.

PubMed

Saito, Mineki; Sejima, Hiroe; Naito, Tadasuke; Ushirogawa, Hiroshi; Matsuzaki, Toshio; Matsuura, Eiji; Tanaka, Yuetsu; Nakamura, Tatsufumi; Takashima, Hiroshi

2017-12-04

Chemokine (C-C motif) ligand 1 (CCL1) is produced by activated monocytes/ macrophages and T-lymphocytes, and acts as a potent attractant for Th2 cells and a subset of T-regulatory (Treg) cells. Previous reports have indicated that CCL1 is overexpressed in adult T-cell leukemia cells, mediating an autocrine anti-apoptotic loop. Because CCL1 is also known as a potent chemoattractant that plays a major role in inflammatory processes, we investigated the role of CCL1 in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The results showed that: (1) CCL1 was preferentially expressed in HAM/TSP-derived HTLV-1-infected T-cell lines, (2) CCL1 expression was induced along with Tax expression in the Tax-inducible T-cell line JPX9, (3) transient Tax expression in an HTLV-1-negative T-cell line activated the CCL1 gene promoter, (4) plasma levels of CCL1 were significantly higher in patients with HAM/TSP than in HTLV-1-seronegative patients with multiple sclerosis and HTLV-1-infected asymptomatic healthy carriers, and (5) minocycline inhibited the production of CCL1 in HTLV-1-infected T-cell lines. The present results suggest that elevated CCL1 levels may be associated with the pathogenesis of HAM/TSP. Although further studies are required to determine the in vivo significance, minocycline may be considered as a potential candidate for the long-term treatment of HAM/TSP via its anti-inflammatory effects, which includes the inhibition of CCL1 expression.

Minocycline blocks asthma-associated inflammation in part by interfering with the T cell receptor-nuclear factor κB-GATA-3-IL-4 axis without a prominent effect on poly(ADP-ribose) polymerase.

PubMed

Naura, Amarjit S; Kim, Hogyoung; Ju, Jihang; Rodriguez, Paulo C; Jordan, Joaquin; Catling, Andrew D; Rezk, Bashir M; Abd Elmageed, Zakaria Y; Pyakurel, Kusma; Tarhuni, Abdelmetalab F; Abughazleh, Mohammad Q; Errami, Youssef; Zerfaoui, Mourad; Ochoa, Augusto C; Boulares, A Hamid

2013-01-18

Minocycline protects against asthma independently of its antibiotic function and was recently reported as a potent poly(ADP-ribose) polymerase (PARP) inhibitor. In an animal model of asthma, a single administration of minocycline conferred excellent protection against ovalbumin-induced airway eosinophilia, mucus hypersecretion, and Th2 cytokine production (IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF) and a partial protection against airway hyperresponsiveness. These effects correlated with pronounced reduction in lung and sera allergen-specific IgE. A reduction in poly(ADP-ribose) immunoreactivity in the lungs of minocycline-treated/ovalbumin-challenged mice correlated with decreased oxidative DNA damage. The effect of minocycline on PARP may be indirect, as the drug failed to efficiently block direct PARP activation in lungs of N-methyl-N'-nitro-N-nitroso-guanidine-treated mice or H(2)O(2)-treated cells. Minocycline blocked allergen-specific IgE production in B cells potentially by modulating T cell receptor (TCR)-linked IL-4 production at the mRNA level but not through a modulation of the IL-4-JAK-STAT-6 axis, IL-2 production, or NFAT1 activation. Restoration of IL-4, ex vivo, rescued IgE production by minocycline-treated/ovalbumin-stimulated B cells. IL-4 blockade correlated with a preferential inhibition of the NF-κB activation arm of TCR but not GSK3, Src, p38 MAPK, or ERK1/2. Interestingly, the drug promoted a slightly higher Src and ERK1/2 phosphorylation. Inhibition of NF-κB was linked to a complete blockade of TCR-stimulated GATA-3 expression, a pivotal transcription factor for IL-4 expression. Minocycline also reduced TNF-α-mediated NF-κB activation and expression of dependent genes. These results show a potentially broad effect of minocycline but that it may block IgE production in part by modulating TCR function, particularly by inhibiting the signaling pathway, leading to NF-κB activation, GATA-3 expression, and subsequent IL-4 production.

Minocycline Blocks Asthma-associated Inflammation in Part by Interfering with the T Cell Receptor-Nuclear Factor κB-GATA-3-IL-4 Axis without a Prominent Effect on Poly(ADP-ribose) Polymerase*

PubMed Central

Naura, Amarjit S.; Kim, Hogyoung; Ju, Jihang; Rodriguez, Paulo C.; Jordan, Joaquin; Catling, Andrew D.; Rezk, Bashir M.; Elmageed, Zakaria Y. Abd; Pyakurel, Kusma; Tarhuni, Abdelmetalab F.; Abughazleh, Mohammad Q.; Errami, Youssef; Zerfaoui, Mourad; Ochoa, Augusto C.; Boulares, A. Hamid

2013-01-01

Minocycline protects against asthma independently of its antibiotic function and was recently reported as a potent poly(ADP-ribose) polymerase (PARP) inhibitor. In an animal model of asthma, a single administration of minocycline conferred excellent protection against ovalbumin-induced airway eosinophilia, mucus hypersecretion, and Th2 cytokine production (IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF) and a partial protection against airway hyperresponsiveness. These effects correlated with pronounced reduction in lung and sera allergen-specific IgE. A reduction in poly(ADP-ribose) immunoreactivity in the lungs of minocycline-treated/ovalbumin-challenged mice correlated with decreased oxidative DNA damage. The effect of minocycline on PARP may be indirect, as the drug failed to efficiently block direct PARP activation in lungs of N-methyl-N′-nitro-N-nitroso-guanidine-treated mice or H2O2-treated cells. Minocycline blocked allergen-specific IgE production in B cells potentially by modulating T cell receptor (TCR)-linked IL-4 production at the mRNA level but not through a modulation of the IL-4-JAK-STAT-6 axis, IL-2 production, or NFAT1 activation. Restoration of IL-4, ex vivo, rescued IgE production by minocycline-treated/ovalbumin-stimulated B cells. IL-4 blockade correlated with a preferential inhibition of the NF-κB activation arm of TCR but not GSK3, Src, p38 MAPK, or ERK1/2. Interestingly, the drug promoted a slightly higher Src and ERK1/2 phosphorylation. Inhibition of NF-κB was linked to a complete blockade of TCR-stimulated GATA-3 expression, a pivotal transcription factor for IL-4 expression. Minocycline also reduced TNF-α-mediated NF-κB activation and expression of dependent genes. These results show a potentially broad effect of minocycline but that it may block IgE production in part by modulating TCR function, particularly by inhibiting the signaling pathway, leading to NF-κB activation, GATA-3 expression, and subsequent IL-4 production. PMID:23184953

Oligodendrocyte death, neuroinflammation, and the effects of minocycline in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION)

PubMed Central

Mehrabian, Zara; Guo, Yan; Weinreich, Daniel

2017-01-01

Purpose Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its models is associated with neurodegenerative inflammation. Minocycline is a tetracycline derivative antibiotic believed to exert a neuroprotective effect by selective alteration and activation of the neuroinflammatory response. We evaluated minocycline’s post-induction ability to modify early and late post-ischemic inflammatory responses and its retinal ganglion cell (RGC)–neuroprotective ability. Methods We used the rodent NAION (rNAION) model in male Sprague-Dawley rats. Animals received either vehicle or minocycline (33 mg/kg) daily intraperitoneally for 28 days. Early (3 days) ON-cytokine responses were evaluated, and oligodendrocyte death was temporally evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. Cellular inflammation was evaluated with immunohistochemistry, and RGC preservation was compared with stereology of Brn3a-positive cells in flat mounted retinas. Results Post-rNAION, oligodendrocytes exhibit a delayed pattern of apoptosis extending over a month, with extrinsic monocyte infiltration occurring only in the primary rNAION lesion and progressive distal microglial activation. Post-induction minocycline failed to improve retinal ganglion cell survival compared with the vehicle treated (893.14 vs. 920.72; p>0.9). Cytokine analysis of the rNAION lesion 3 days post-induction revealed that minocycline exert general inflammatory suppression without selective upregulation of cytokines associated with the proposed alternative or neuroprotective M2 inflammatory pathway. Conclusions The pattern of cytokine release, extended temporal window of oligodendrocyte death, and progressive microglial activation suggests that selective neuroimmunomodulation, rather than general inflammatory suppression, may be required for effective repair strategies in ischemic optic neuropathies. PMID:29386871

Increased Staphylococcus-killing activity of an antimicrobial peptide, lactoferricin B, with minocycline and monoacylglycerol.

PubMed

Wakabayashi, Hiroyuki; Teraguchi, Susumu; Tamura, Yoshitaka

2002-10-01

This study aimed to find antibiotics or other compounds that could increase the antimicrobial activity of an antimicrobial peptide, lactoferricin B (LFcin B), against Staphylococcus aureus, including antibiotic-resistant strains. Among conventional antibiotics, minocycline increased the bactericidal activity of LFcin B against S. aureus, but methicillin, ceftizoxime, and sulfamethoxazole-trimethoprim did not have such an effect. The combination of minocycline and LFcin B had synergistic effects against three antibiotic-resistant strains of S. aureus, according to result of checkerboard analysis. Screening of 33 compounds, including acids and salts, alcohols, amino acids, proteins and peptides, sugar, and lipids, showed that medium-chain monoacylglycerols increased the bactericidal activity of LFcin B against three S. aureus strains. The short-term killing test in water and the killing curve test in growing cultures showed that a combination of LFcin B and monolaurin (a monoacylglycerol with a 12-carbon acyl chain) killed S. aureus more rapidly than either agent alone. These findings may be helpful in the application of antimicrobial peptides in medical or other situations.

Treatment of the psychiatric problems associated with fragile X syndrome.

PubMed

Hagerman, Randi J; Polussa, Jonathan

2015-03-01

This work reviews recent research regarding treatment of fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder. The phenotype includes anxiety linked to sensory hyperarousal, hyperactivity, and attentional problems consistent with attention deficit hyperactivity disorder and social deficits leading to autism spectrum disorder in 60% of boys and 25% of girls with FXS. Multiple targeted treatments for FXS have rescued the phenotype of the fmr1 knockout mouse, but few have been beneficial to patients with FXS. The failure of the metabotropic glutamate receptor 5 antagonists falls on the heels of the failure of Arbaclofen's efficacy in children and adults with autism or FXS. In contrast, efficacy has been demonstrated in a controlled trial of minocycline in children with FXS. Minocycline lowers the abnormally elevated levels of matrix metalloproteinase 9 in FXS. Acamprosate and lovastatin have been beneficial in open-label trials in FXS. The first 5 years of life may be the most efficacious time for intervention when combined with behavioral and/or educational interventions. Minocycline, acamprosate, lovastatin, and sertraline are treatments that can be currently prescribed and have shown benefit in children with FXS. Use of combined medical and behavioral interventions will likely be most efficacious for the treatment of FXS.

Adult Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Acute myeloid leukemia (AML; also called acute myelogenous leukemia, acute nonlymphocytic leukemia) treatment advances have resulted in substantially improved CR rates. Cytogenetic analysis helps predict outcomes of treatment which includes chemotherapy, radiation, and stem cell transplant. Get detailed information about AML in this clinician summary.

Cryotherapy and Topical Minocycline as Adjunctive Measures to Control Pain After Third Molar Surgery: An Exploratory Study

PubMed Central

Gelesko, Savannah; Long, Leann; Faulk, Jan; Phillips, Ceib; Dicus, Carolyn; White, Raymond P.

2013-01-01

Purpose To assess the impact of cryotherapy or topical minocycline on patients’ perceptions of recovery from pain after third molar surgery in an exploratory comparative-effectiveness study. Patients and Methods Subjects aged at least 14 years who were having all 4 third molars removed were enrolled in 3 separate institutional review board–approved studies. Study groups included subjects treated with a passively applied cold wrap for 24 hours postoperatively, subjects treated with topical minocycline during surgery, and subjects enrolled in a nonconcurrent comparison group who had received neither topical minocycline nor directed cryotherapy. Third molar surgery was performed in all cases by trained surgeons using the same protocol. An exact Kruskal-Wallis test was used to compare the distributions of the worst and average pain scores and a Fisher exact test to compare verbal responses from Gracely pain scales among the 3 groups for postsurgical days (PSDs) 1 to 3. Results This study comprised 51 cryotherapy subjects (2005–2009), 63 minocycline subjects (2003–2004), and 92 comparison-group subjects (2002–2006) who were treated at academic centers and in community practices across the United States (N = 206). Demographic descriptors were similar among all groups. For PSDs 1 through 3 (unadjusted), the highest scores for worst pain (6–7 [out of 7] on Likert-type scale) were reported less frequently in each of the study groups than in subjects in the comparison group, although the numbers of subjects reporting the highest scores were few. The distribution of pain outcomes was significantly different among the 3 groups for worst pain and affective words on PSD 1 (P = .04 for both). However, the small number of subjects who reported the highest pain scores precluded adequate multivariate statistical analyses for all outcomes on PSD 1 to 3. Conclusions Data from this exploratory study suggest that adjunctive therapy to decrease postoperative pain�

Systemic antimicrobial therapy (minocycline) as an adjunct to non-surgical approach to recurrent chronic generalized gingival hyperplasia.

PubMed

Khatri, Parag M; Bacha, Shraddanand

2014-03-01

Systemic antibiotic treatment has emerged as a powerful adjunct to conventional mechanical debridement for therapeutic management of the periodontal diseases. The conceptual basis for treating periodontal diseases as infections is particularly attractive in part because of substantial data indicating that these diseases may be associated with specific putative pathogens. Further, discrete groups of patients respond well to systemic antibiotics and exhibit improvement of clinical parameters, including attachment level and inflammation. This bacterial-host interaction, which is ever-so-present in periodontitis, directs us toward utilizing antimicrobial agents along with the routine mechanical debridement. This case report presents a case of a female patient with recurrence of the chronic generalized periodontitis with gingival enlargement, which is treated thrice by referral dentist. A through clinical examination was carried out pre-operatively and treatment was planned with systemic minocycline in conjunction with the conventional non-surgical approach. There was a significant reduction of pocket depth, gain in attachment with dramatic improvement clinically.

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult Acute Lymphoblastic Leukemia (ALL; also called acute lymphocytic leukemia) is an aggressive cancer that can progress quickly without treatment. Treatments include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about the molecular genetics, prognosis, and treatment of ALL in this clinician summary.

Doxycycline as an inhibitor of p-glycoprotein in the alpaca for the purpose of maintaining avermectins in the CNS during treatment for parelaphostrongylosis.

PubMed

Agbedanu, Prince N; Anderson, Kristi L; Brewer, Matthew T; Carlson, Steve A

2015-09-15

Meningeal worms (Parelaphostrongylus tenuis) are a common malady of alpacas, often refractory to conventional treatments. Ivermectin is a very effective anthelmintic used against a variety of parasites but this drug is not consistently effective against alpaca meningeal worms once the parasite has gained access to the CNS, even if used in a protracted treatment protocol. Ivermectin is not effective against clinical cases of P. tenuis, raising the possibility that the drug is not sustained at therapeutic concentrations in the central nervous system (CNS). A specific protein (designated as p-glycoprotein (PGP)) effluxes ivermectin from the brain at the blood-brain barrier, thus hampering the maintenance of therapeutic concentrations of the drug in the CNS. Minocycline is a synthetic tetracycline antibiotic with an excellent safety profile in all animals tested to date. Minocycline has three unique characteristics that could be useful for treating meningeal worms in conjunction with ivermectin. First, minocycline is an inhibitor of PGP at the blood-brain barrier and this inhibition could maintain effective concentrations of ivermectin in the brain and meninges. Second, minocycline protects neurons in vivo through a number of different mechanisms and this neuroprotection could alleviate the potential untoward neurologic effects of meningeal worms. Third, minocycline is a highly lipid-soluble drug, thus facilitating efficient brain penetration. We thus hypothesized that minocycline will maintain ivermectin, or a related avermectin approved in ruminants (abamectin, doramectin, or eprinomectin), in the alpaca CNS. To test this hypothesis, we cloned the gene encoding the alpaca PGP, expressed the alpaca PGP in a heterologous expression system involving MDCK cells, and measured the ability of minocycline to inhibit the efflux of avermectins from the MDCK cells; doxycycline was used as a putative negative control (based on studies in other species). Our in vitro studies

Home treatment for acute psychiatric illness.

PubMed

Dean, C; Gadd, E M

1990-11-03

To determine the factors influencing the successful outcome of community treatment for severe acute psychiatric illnesses that are traditionally treated in hospital. All patients from a single electoral ward who were either admitted to hospital or treated at home over a two year period (1 October 1987 to 30 September 1989) were included in the study and their case notes audited. The second year of the study is reported. Electoral ward of Sparkbrook, Birmingham. 99 Patients aged 16-65 with severe acute psychiatric illness. 65 Patients were managed by home treatment alone; 34 required admission to hospital. The location of treatment was significantly (all p less than 0.05) influenced by social characteristics of the patients (marital state, age (in men), ethnicity, and living alone) and by characteristics of the referral (occurring out of hours; assessment taking place at hospital or police station). DSM-III-R diagnosis was more weakly associated with outcome. Violence during the episode was significantly related to admission, although deliberate self harm was not. Home treatment is feasible for most patients with acute psychiatric illness. A 24 hour on call assessment service increases the likelihood of success because admission is determined more strongly by social characteristics of the patient and the referral than by illness factors. Admission will still be required for some patients. A locally based mental health resource centre, a 24 hour on call service, an open referral system, and an active follow up policy increase the effectiveness of a home treatment service.

Home treatment for acute psychiatric illness.

PubMed Central

Dean, C; Gadd, E M

1990-01-01

OBJECTIVE--To determine the factors influencing the successful outcome of community treatment for severe acute psychiatric illnesses that are traditionally treated in hospital. DESIGN--All patients from a single electoral ward who were either admitted to hospital or treated at home over a two year period (1 October 1987 to 30 September 1989) were included in the study and their case notes audited. The second year of the study is reported. SETTING--Electoral ward of Sparkbrook, Birmingham. SUBJECTS--99 Patients aged 16-65 with severe acute psychiatric illness. RESULTS--65 Patients were managed by home treatment alone; 34 required admission to hospital. The location of treatment was significantly (all p less than 0.05) influenced by social characteristics of the patients (marital state, age (in men), ethnicity, and living alone) and by characteristics of the referral (occurring out of hours; assessment taking place at hospital or police station). DSM-III-R diagnosis was more weakly associated with outcome. Violence during the episode was significantly related to admission, although deliberate self harm was not. CONCLUSIONS--Home treatment is feasible for most patients with acute psychiatric illness. A 24 hour on call assessment service increases the likelihood of success because admission is determined more strongly by social characteristics of the patient and the referral than by illness factors. Admission will still be required for some patients. A locally based mental health resource centre, a 24 hour on call service, an open referral system, and an active follow up policy increase the effectiveness of a home treatment service. PMID:2249049

A minocycline-releasing PMMA system as a space maintainer for staged bone reconstructions-in vitro antibacterial, cytocompatibility and anti-inflammatory characterization.

PubMed

Silva, Tiago; Grenho, Liliana; Barros, Joana; Silva, José Carlos; Pinto, Rosana V; Matos, Ana; Colaço, Bruno; Fernandes, Maria Helena; Bettencourt, Ana; Gomes, Pedro S

2017-06-06

In the present work, we study the development and biological characterization of a polymethyl methacrylate (PMMA)-based minocycline delivery system, to be used as a space maintainer within craniofacial staged regenerative interventions. The developed delivery systems were characterized regarding solid state characteristics and assayed in vitro for antibacterial and anti-inflammatory activity, and cytocompatibility with human bone cells. A drug release profile allowed for an initial burst release and a more sustained and controlled release over time, with minimum inhibitory concentrations for the assayed and relevant pathogenic bacteria (i.e., Staphylococcus aureus, slime-producer Staphylococcus epidermidis and Escherichia coli) being easily attained in the early time points, and sustained up to 72 h. Furthermore, an improved osteoblastic cell response-with enhancement of cell adhesion and cell proliferation-and increased anti-inflammatory activity were verified in developed systems, compared to a control (non minocycline-loaded PMMA cement). The obtained results converge to support the possible efficacy of the developed PMMA-based minocycline delivery systems for the clinical management of complex craniofacial trauma. Here, biomaterials with space maintenance properties are necessary for the management of staged reconstructive approaches, thus minimizing the risk of peri-operative infections and enhancing the local tissue healing and early stages of regeneration.

The Effect of Pleural Abrasion on the Treatment of Primary Spontaneous Pneumothorax: A Systematic Review of Randomized Controlled Trials

PubMed Central

Ming, Mo-yu; Cai, Shuang-qi; Chen, Yi-Qiang

2015-01-01

Background Pleural abrasion has been widely used to control the recurrence of primary spontaneous pneumothorax (PSP). However, controversy still exists regarding the advantages and disadvantages of pleural abrasion compared with other interventions in preventing the recurrence of PSP. Methods The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 15, 2014 to identify randomized controlled trials (RCTs) that compared the effects of pleural abrasion with those of other interventions in the treatment of PSP. The study outcomes included the PSP recurrence rate and the occurrence rate of adverse effects. Results Mechanical pleural abrasion and apical pleurectomy after thoracoscopic stapled bullectomy exhibited similarly persistent postoperative air leak occurrence rates (p = 0.978) and 1-year PSP recurrence rates (p = 0.821), whereas pleural abrasion led to reduced residual chest pain and discomfort (p = 0.001) and a smaller rate of hemothorax (p = 0.036) than did apical pleurectomy. However, the addition of minocycline pleurodesis to pleural abrasion did not reduce the pneumothorax recurrence rate compared with apical pleurectomy (3.8% for both procedures) but was associated with fewer complications. There was no statistical difference in the pneumothorax recurrence rate between mechanical pleural abrasion and chemical pleurodesis with minocycline on either an intention-to-treat basis (4 of 42 versus 0 of 42, p = 0.12; Fisher exact test) or after exclusions (2 of 40 versus 0 of 42, p = 0.24; Fisher exact test). Pleural abrasion plus minocycline pleurodesis also did not reduce the pneumothorax recurrence rate compared with pleural abrasion alone (p = 0.055). Moreover, pleural abrasion plus minocycline pleurodesis was associated with more intense acute chest pain. The postoperative overall recurrence rate in patients who underwent staple line coverage with absorbable cellulose mesh and fibrin glue was similar to that

Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing

PubMed Central

O'Collins, Victoria E; Macleod, Malcolm R; Cox, Susan F; Van Raay, Leena; Aleksoska, Elena; Donnan, Geoffrey A; Howells, David W

2011-01-01

There is some evidence that in animal models of acute ischaemic stroke, combinations of neuroprotective agents might be more efficacious than the same agents administered alone. Hence, we developed pragmatic, empirical criteria based on therapeutic target, cost, availability, efficacy, administration, and safety to select drugs for testing in combination in animal models of acute stroke. Magnesium sulphate, melatonin, and minocycline were chosen from a library of neuroprotective agents, and were tested in a more ‘realistic' model favoured by the STAIR (Stroke Therapy Academic Industry Roundtable). Outcome was assessed with infarct volume, neurologic score, and two newly developed scales measuring general health and physiologic homeostasis. Owing to the failure to achieve neuroprotection in aged, hypertensive animals with drug delivery at 3 hours, the bar was lowered in successive experiments to determine whether neuroprotection could be achieved under conditions more conducive to recovery. Testing in younger animals showed more favourable homeostasis and general health scores than did testing in older animals, but infarct volume and neurologic scores did not differ with age, and treatment efficacy was again not shown. Testing with shorter occlusions resulted in smaller infarct volumes; nevertheless, treatment efficacy was still not observed. It was concluded that this combination, in these stroke models, was not effective. PMID:20978519

Cardiac transcriptional response to acute and chronic angiotensin II treatments.

PubMed

Larkin, Jennie E; Frank, Bryan C; Gaspard, Renee M; Duka, Irena; Gavras, Haralambos; Quackenbush, John

2004-07-08

Exposure of experimental animals to increased angiotensin II (ANG II) induces hypertension associated with cardiac hypertrophy, inflammation, and myocardial necrosis and fibrosis. Some of the most effective antihypertensive treatments are those that antagonize ANG II. We investigated cardiac gene expression in response to acute (24 h) and chronic (14 day) infusion of ANG II in mice; 24-h treatment induces hypertension, and 14-day treatment induces hypertension and extensive cardiac hypertrophy and necrosis. For genes differentially expressed in response to ANG II treatment, we tested for significant regulation of pathways, based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Microarray Pathway Profiler (GenMAPP) databases, as well as functional classes based on Gene Ontology (GO) terms. Both acute and chronic ANG II treatments resulted in decreased expression of mitochondrial metabolic genes, notably those for the electron transport chain and Krebs-TCA cycle; chronic ANG II treatment also resulted in decreased expression of genes involved in fatty acid metabolism. In contrast, genes involved in protein translation and ribosomal activity increased expression following both acute and chronic ANG II treatments. Some classes of genes showed differential response between acute and chronic ANG II treatments. Acute treatment increased expression of genes involved in oxidative stress and amino acid metabolism, whereas chronic treatments increased cytoskeletal and extracellular matrix genes, second messenger cascades responsive to ANG II, and amyloidosis genes. Although a functional linkage between Alzheimer disease, hypertension, and high cholesterol has been previously documented in studies of brain tissue, this is the first demonstration of induction of Alzheimer disease pathways by hypertension in heart tissue. This study provides the most comprehensive available survey of gene expression changes in response to acute and chronic ANG II treatment, verifying

Optimal antimicrobial catheter lock solution, using different combinations of minocycline, EDTA, and 25-percent ethanol, rapidly eradicates organisms embedded in biofilm.

PubMed

Raad, Issam; Hanna, Hend; Dvorak, Tanya; Chaiban, Gassan; Hachem, Ray

2007-01-01

Antimicrobial lock solutions may be needed to salvage indwelling catheters in patients requiring continuous intravenous therapy. We determined the activity of minocycline, EDTA, and 25% ethanol, alone or in combination, against methicillin-resistant Staphylococcus aureus and Candida parapsilosis catheter-related bloodstream infection strains in two established models of biofilm colonization. Biofilm-colonized catheter segments from a modified Robbins device and a silicone disk biofilm colonization model were exposed to these antimicrobial agents for 15 or 60 min, respectively. After exposure, segments were sonicated and cultured. To determine regrowth after incubation at 37 degrees C, following the brief exposure to the antimicrobial agents, an equal number of segments were washed, reincubated for 24 h, and then sonicated and cultured. The triple combination of minocycline-EDTA (M-EDTA) in 25% ethanol was the only antimicrobial lock solution that completely eradicated S. aureus and C. parapsilosis in biofilm of all segments tested in the two models, and it completely prevented regrowth. In addition, M-EDTA in 25% ethanol was significantly more effective in rapidly eradicating the growth or regrowth of methicillin-resistant S. aureus and C. parapsilosis biofilm colonization in the two models than the other solutions--minocycline, EDTA, M-EDTA, 25% ethanol, and EDTA in ethanol. We conclude that M-EDTA in 25% ethanol is highly effective at rapidly eradicating S. aureus and C. parapsilosis embedded in biofilm adhering to catheter segments.

[Acute lithium poisoning: epidemiology, clinical characteristics, and treatment].

PubMed

Burguera Vion, Víctor; Montes, José Manuel; Del Rey, José Manuel; Rivera-Gorrín, Maite; Rodao, José María; Tenorio, Maite; Saiz-Ruiz, Jerónimo; Liaño, Fernando

2017-02-01

Lithium continues to be the treatment of choice for bipolar disorder. Acute lithium poisoning is a potentially serious event. We present a retrospective observational significative study of episodes of acute lithium poisoning during a 52- month period. Poisoning was defined by a blood lithium concentration of 1.5 mEq/L or higher. We analyzed treatment and epidemiologic and clinical characteristics of 70 episodes were identified (incidence density among treated patients, 1.76 per 100 patient-years). The most frequent cause of lithium poisoning was a concurrent medical condition (46%). Most poisonings were mild (74.2%), but neurologic involvement was identified in 40.3%. Electrocardiographic abnormalities were found in 8 cases. Acute renal failure, found in 23 patients (37.1%), was mild in most cases, although 11 patients required hemodialysis. We concluded that acute lithium poisoning is an uncommon complication, but risk needs to be lowered. Patients should be warned to avoid dosage errors and to take special care during concurrent illnesses and while taking other medications.

Minocycline encapsulated chitosan nanoparticles for central antinociceptive activity.

PubMed

Nagpal, Kalpana; Singh, S K; Mishra, D N

2015-01-01

The purpose of the study is to explore the central anti-nociceptive activity of brain targeted nanoparticles (NP) of minocycline hydrochloride (MH). The NP were formulated using the modified ionotropic gelation method (MHNP) and were coated with Tween 80 (T80) to target them to brain (cMHNP). The formulated nanoparticles have already been characterized for particle size, zeta potential, drug entrapment efficiency and in vitro drug release. The nanoparticles were then evaluated for pharmacodynamic activity using thermal methods. The pure drug and the formulation, MHNP were not able to show a statistically significant central analgesic activity. cMHNP on the other hand evidenced a significant central analgesic activity. Animal models evidenced that brain targeted nanoparticles may be utilized for effective delivery of central anti-nociceptive effect of MH. Further clinical studies are required to explore the activity for mankind. Copyright © 2014 Elsevier B.V. All rights reserved.

[Sub-acute thyroiditis in a patient on immunosuppressive treatment].

PubMed

D'Amico, Giovanna; Di Crescenzo, Vincenzo; Caleo, Alessia; Garzi, Alfredo; Vitale, Mario

2013-01-01

Sub-acute thyroiditis or De Quervain's thyroiditis is a viral, inflammatory disease which causes the serum release of thyroidal hormones and hyperthyroidism. The pathogenesis of thyroid follicle damage is unclear because the exclusive viral action or a concomitant autoimmune component, determined by the lymphoid infiltrate remain to be assessed. We describe the case of a patient under immunosuppressive treatment, who developed sub-acute thyroiditis with hormone release and hyperthyroidism. The patient, while was under immunosuppressive treatment for kidney transplant, exhibited a clinical picture and hormonal profile of hyperthyroidism. Thyroid scintiscan exhibited an extremely low uptake. Fine-needle cytologic diagnosis was granulomatous sub-acute thyroiditis (De Quervain's thyroiditis). This case suggests the primary or even exclusive role of the viral infection in hormone release and hyperthyroidism in sub-acute thyroiditis, excluding an autoimmune component.

Re-evaluating the treatment of acute optic neuritis

PubMed Central

Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

2015-01-01

Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis. Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite ‘normal’ (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury. In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration. In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. PMID:25355373

Cost considerations of acute migraine treatment.

PubMed

Adelman, James U; Adelman, Leon C; Freeman, Marshall C; Von Seggern, Randal L; Drake, Jaclyn

2004-03-01

To provide medication price data and cost-reducing strategies for the acute treatment of migraine. Retail prices for common acute care medications were found at http://www.drugstore.com. Cost-reduction tactics were obtained from literature searches and clinical experience. Several strategies can reduce cost without sacrificing treatment outcome. In mild to moderate migraine, low-priced nonsteroidal anti-inflammatory drugs can be used as first-line medications due to their proven efficacy and favorable tolerability. For patients with more severe migraine, implementing a stratified care approach-using migraine-specific medications early in acute treatment-is cost-effective for most patients. Stratified care not only improves outcome and decreases disability, but also reduces cost. Pill splitting and early administration of triptans within an attack enhance their value. Supplying rescue medications, such as opioids, sedatives, and phenothiazines, can prevent emergency department visits. Minimizing multiple dosing of triptans and reducing utilization of expensive health care resources are key factors in reducing the cost of effective migraine treatment. An important affordability factor for patients with co-payments is the number of triptan pills per package. Sumatriptan, naratriptan, and frovatriptan each contain 9 tablets per package, while most other triptan packages contain 6. Current triptan retail prices (per unit) include: Amerge 1 and 2.5 mg, 17.78 dollars; Axert 6.25 and 12.5 mg, 16.31 dollars; Frova 2.5 mg, 13.89 dollars; Imitrex 50 mg, 14.96 dollars; Imitrex 100 mg, 14.41 dollars; Imitrex Nasal Spray 20 mg, 21.61 dollars; Imitrex SQ 6 mg, 50.26 dollars; Maxalt 5 and 10 mg, 15 dollars; Maxalt-MLT 5 and 10 mg, 15 dollars; Relpax 40 mg, 13.58 dollars; Zomig 2.5 mg, 13.67 dollars; Zomig 5 mg, 15.89 dollars; Zomig-ZMT 2.5 mg, 13.67 dollars; and Zomig-ZMT 5 mg, 15.89 dollars. Practitioners can optimize the use of health care dollars without compromising quality of

A systematic review on the treatment of acute ankle sprain: brace versus other functional treatment types.

PubMed

Kemler, Ellen; van de Port, Ingrid; Backx, Frank; van Dijk, C Niek

2011-03-01

Ankle injuries, especially ankle sprains, are a common problem in sports and medical care. Ankle sprains result in pain and absenteeism from work and/or sports participation, and can lead to physical restrictions such as ankle instability. Nowadays, treatment of ankle injury basically consists of taping the ankle. The purpose of this review is to evaluate the effectiveness of ankle braces as a treatment for acute ankle sprains compared with other types of functional treatments such as ankle tape and elastic bandages. A computerized literature search was conducted using PubMed, EMBASE, CINAHL and the Cochrane Clinical Trial Register. This review includes randomized controlled trials in English, German and Dutch, published between 1990 and April 2009 that compared ankle braces as a treatment for lateral ankle sprains with other functional treatments. The inclusion criteria for this systematic review were (i) individuals (sports participants as well as non-sports participants) with an acute injury of the ankle (acute ankle sprains); (ii) use of an ankle brace as primary treatment for acute ankle sprains; (iii) control interventions including any other type of functional treatment (e.g. Tubigrip™, elastic wrap or ankle tape); and (iv) one of the following reported outcome measures: re-injuries, symptoms (pain, swelling, instability), functional outcomes and/or time to resumption of sports, daily activities and/or work. Eight studies met all inclusion criteria. Differences in outcome measures, intervention types and patient characteristics precluded pooling of the results, so best evidence syntheses were conducted. A few individual studies reported positive outcomes after treatment with an ankle brace compared with other functional methods, but our best evidence syntheses only demonstrated a better treatment result in terms of functional outcome. Other studies have suggested that ankle brace treatment is a more cost-effective method, so the use of braces after acute

Topical nitroglycerin ointment for treatment of acute hypertension in hospitalized inpatients.

PubMed

Brower, Kathryn A; Garcia, Nelson A Telles; Smith, Hayden L; Wall, Geoffrey C

2015-05-01

Hypertension in the hospital setting is common; however, guidelines provide limited guidance specific to the inpatient setting. Acute antihypertensive treatment options can be limited in this setting by monitoring requirements of intravenous medications and patients' inability to take oral medications. A possible treatment choice used to treat acute hypertension is nitroglycerin ointment. Nitroglycerin is not approved by the Food and Drug Administration for this condition, and limited evidence exists to support this indication. To evaluate the statistical and clinical effectiveness of nitroglycerin ointment as a treatment option for acute hypertension based on a 20 mm Hg or greater reduction in systolic blood pressure. A retrospective chart review at a large tertiary community teaching hospital was performed on all adult noncardiac inpatients with an episode of acute hypertension that resulted in the administration of nitroglycerin ointment. Seventy-two patients met inclusion criteria with a total of 112 applications of nitroglycerin ointment. Of the 112 applications, systolic blood pressure decreased 20 mm Hg or more in 42% of occurrences with a median decrease of 16 mm Hg. Study results suggest possible efficacy of nitroglycerin ointment for the treatment of acute hypertension in noncardiac hospitalized patients. © The Author(s) 2014.

Effects of acute and chronic cilazapril treatment in spontaneously hypertensive rats

PubMed Central

Fischli, W.; Hefti, F.; Clozel, J.-P.

1989-01-01

1 The effects of acute and chronic treatment with cilazapril, a new ACE inhibitor, on peripheral vasculature and renal excretory function were assessed in spontaneously hypertensive rats. Regional blood flow and cardiac output were measured by the radio-active microspheres technique. 2 Acute treatment (3 mg kg-1 intravenously) reduced mean arterial blood pressure from 171 ± 7 to 140 241 ± 7 mm Hg (P < 0.001), chronic treatment (1 × 10 mg kg-1 day-1 orally for 9 weeks) from 191 ± 5 to 122 ± 3 mm Hg P < 0.001). With both kinds of treatments cardiac output was unchanged. Heart rate was slightly decreased (-9%, P < 0.05) with chronic treatment. Acutely, the main effect of cilazapril was a decrease of the renal vascular resistance (-41%, P < 0.001) associated with an increase of the fraction of the cardiac output distributed to the kidney (+46%, P < 0.001). Chronically, cilazapril decreased regional vascular resistance in most of the peripheral vascular beds except the heart. 3 With a high dose of cilazapril (10 mg kg-1 orally) both acute and chronic treatment increased diuresis (+107% and +92%, P < 0.001) and natriuresis (+124% and +111%, P < 0.001) with a slight increase in kaliuresis. However, with a low dose (1 mg kg-1 orally) the kidneys responded only to chronic treatment. 4 It is concluded that chronic treatment with cilazapril decreases arterial blood pressure more than acute treatment. This effect seems to be due to a greater peripheral vasodilation. In addition, diuretic and natriuretic effects of cilazapril probably contribute to blood pressure reduction. PMID:2527529

Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study

ERIC Educational Resources Information Center

Kafantaris, Vivian; Coletti, Daniel J.; Dicker, Robert; Padula, Gina; Pleak, Richard R.; Alvir, Jose Ma. J.; Kane, John M.

2004-01-01

Objective: There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents. Method: In this discontinuation study, participants received open treatment with lithium at…

Appropriate treatment of acute sigmoid volvulus in the emergency setting

PubMed Central

Lou, Zheng; Yu, En-Da; Zhang, Wei; Meng, Rong-Gui; Hao, Li-Qiang; Fu, Chuan-Gang

2013-01-01

AIM: To investigate an appropriate strategy for the treatment of patients with acute sigmoid volvulus in the emergency setting. METHODS: A retrospective review of 28 patients with acute sigmoid volvulus treated in the Department of Colorectal Surgery, Changhai Hospital, Shanghai from January 2001 to July 2012 was performed. Following the diagnosis of acute sigmoid volvulus, an initial colonoscopic approach was adopted if there was no evidence of diffuse peritonitis. RESULTS: Of the 28 patients with acute sigmoid volvulus, 19 (67.9%) were male and 9 (32.1%) were female. Their mean age was 63.1 ± 22.9 years (range, 21-93 years). Six (21.4%) patients had a history of abdominal surgery, and 17 (60.7%) patients had a history of constipation. Abdominal radiography or computed tomography was performed in all patients. Colonoscopic detorsion was performed in all 28 patients with a success rate of 92.8% (26/28). Emergency surgery was required in the other two patients. Of the 26 successfully treated patients, seven (26.9%) had recurrent volvulus. CONCLUSION: Colonoscopy is the primary emergency treatment of choice in uncomplicated acute sigmoid volvulus. Emergency surgery is only for patients in whom nonoperative treatment is unsuccessful, or in those with peritonitis. PMID:23946604

Re-evaluating the treatment of acute optic neuritis.

PubMed

Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

2015-07-01

Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite 'normal' (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury.In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration.In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Use of minocycline as systemic antimicrobial therapy in refractory periodontitis with chronic gingival enlargement.

PubMed

Khatri, Parag M; Kumar, Rajesh

2012-01-01

Periodontal disease is a multifactorial disease having various risk factors, but a dynamic interaction between bacterial products and host response in association with genetic and environmental factors is considered as the primary cause for periodontal tissue destruction in periodontitis. This bacterial-host interaction which is ever-so-present in periodontitis directs us toward utilizing antimicrobial agents along with the routine mechanical debridement. This case report present a case of a female patient with recurrent periodontal infections with gingival enlargement treated with systemic Minocycline in conjunction with the conventional non-surgical approach.

Treatment of acute pancreatitis with mexidol and low-intensity laser radiation

NASA Astrophysics Data System (ADS)

Parzyan, G. R.; Geinits, A. V.

2001-04-01

This article presents the results of treatment of 54 patients with acute pancreatitis. The patients were divided into two groups according to the method of treatment. The control group (26 patients) received a conventional therapy, whereas the experimental group (28 patients) received mexidol in combination with the intravenous laser irradiation of blood. Clinical and laboratory tests confirmed a high efficiency of the combined therapy based on the administration of mexidol antioxidant and low-intensity (lambda) equals 0.63 micrometers diode laser irradiation of blood. This therapeutic technique produced an influence on the basic pathogenetic mechanisms of acute pancreatitis. The application of this method of treatment improved the course and prognosis of acute pancreatitis.

Treatment of acute diarrhea with Saccharomyces boulardii in infants.

PubMed

Corrêa, Naflesia B O; Penna, Francisco J; Lima, Fátima M L S; Nicoli, Jacques R; Filho, Luciano A P

2011-11-01

The aim of the study was to determine whether an oral treatment with a commercial pharmaceutical product containing Saccharomyces boulardii would reduce the duration of diarrhea in infants with acute diarrhea. In the present double-blind, placebo-controlled study, 186 infants, 6 to 48 months old and hospitalized within 72 hours after the onset of acute diarrhea in 2 hospitals in Goiânia, Goiás, Brazil, were randomly assigned to receive twice per day for 5 days 200 mg of a commercial pharmaceutical product containing 4 × 10 viable cells of S boulardii or a placebo. Stool samples were submitted to search for rotavirus. Among the 176 infants who completed the trial, those treated with S boulardii (90) showed a reduction in diarrhea duration (P < 0.05) when compared with the placebo group (86). The present study shows a reduction in diarrhea duration when S boulardii was given to children within 72 hours after the onset of acute diarrhea. The present study suggests a complementary treatment of acute diarrhea in infants with daily oral doses of S boulardii.

[System evaluation on Ginkgo Biloba extract in the treatment of acute cerebral infarction].

PubMed

Wang, Lin; Zhang, Tao; Bai, Kezhen

2015-10-01

To evaluate the effect and safety of Ginkgo Biloba extract on the treatment of acute cerebral infarction.
 The Database of Wanfang, China National Knowledge Infrastructure (CNKI) and VIPU were screened for literatures regarding Ginkgo Biloba extract in the treatment of acute cerebral infarction, including the clinical randomized controlled trials. Meta-analysis based on the Revman 4.2 system was performed.
 Compared with the control group, treatment with Ginkgo Biloba extract enhanced efficacy in the treatment of acute cerebral infarction (OR: 1.60-5.53), which displayed an improved neural function defect score [WMD -3.12 (95%CI: -3.96- -2.28)].
 Ginkgo Biloba extract is beneficial to the improvement of neurological function in patients with acute cerebral infarction and it is safe for patients.

Pan Canadian Rash Trial: A Randomized Phase III Trial Evaluating the Impact of a Prophylactic Skin Treatment Regimen on Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-Induced Skin Toxicities in Patients With Metastatic Lung Cancer.

PubMed

Melosky, Barbara; Anderson, Helen; Burkes, Ronald L; Chu, Quincy; Hao, Desiree; Ho, Vincent; Ho, Cheryl; Lam, Wendy; Lee, Christopher W; Leighl, Natasha B; Murray, Nevin; Sun, Sophie; Winston, Robert; Laskin, Janessa J

2016-03-10

Erlotinib is an epidermal growth factor receptor inhibitor approved for patients with advanced non-small-cell lung cancer (NSCLC) whose epidermal growth factor receptor expression status is positive or unknown. Although it is efficacious, erlotinib can cause skin toxicity. This prospective, randomized phase III trial examined the effect of prophylactic treatment of erlotinib-induced skin rash. Patients receiving erlotinib in the second- or third-line setting for advanced NSCLC were randomly assigned to prophylactic minocycline (100 mg twice per day for 4 weeks), reactive treatment (after rash developed, per grade of rash), or no treatment unless severe (grade 3). Rash incidence and severity, time to maximal rash, time to resolution, and overall survival (OS) were compared among treatment groups. In all, 150 patients were randomly assigned, 50 to each of three treatment arms. The incidence of skin toxicity was 84% regardless of treatment arm. Prophylactic treatment with minocycline significantly lengthened the time to the most severe grade of rash. Grade 3 rash was significantly higher in the no-treatment arm. OS was not significantly different among treatment arms, but patients receiving prophylactic or reactive treatments had a longer OS (7.6 and 8 months, respectively) than those who received no rash treatment (6 months). Rash was not self-limiting. The incidence of all grades of rash did not differ statistically among the three arms, so the trial was negative. The incidence of grade 3 skin toxicities was reduced in patients who were treated with prophylactic minocycline or reactive treatment. Efficacy was not compromised. Prophylactic minocycline and reactive treatment are both acceptable options for the necessary treatment of erlotinib-induced rash in the second- or third-line setting of metastatic NSCLC. © 2015 by American Society of Clinical Oncology.

Design of minocycline-containing starch nanocapsules for topical delivery.

PubMed

Marto, J; Gouveia, L F; Gonçalves, L M; Ribeiro, H M; Almeida, A J

2018-06-11

Pharmaceutical research has been focused on developing improved delivery systems while exploring new ways of using approved excipients. The present work investigated the potential of starch nanocapsules (StNC) as a topical delivery platform for hydrophilic antimicrobial drugs using minocycline hydrochloride (MH) as a model drug. Thus, a quality by design approach was used to assess the role of different factors that affect the main pharmaceutical properties of StNC prepared using an emulsification-solvent evaporation method. Full characterization was performed in terms of particle size, encapsulation efficiency, morphology and physical stability at 5 ± 3°C. Results show the surfactant and lipid contents play a major role in StNC particle size distribution. The MH loading only promoted minor changes upon StNC properties. Formulations were stable without variations on physicochemical properties. All tested formulations presented a zeta potential of +33.6±6.7 mV, indicating a good physical stability and evidencing that StNC are suitable nanocarriers for topical use.

Outcomes after treatment of acute aortic occlusion.

PubMed

de Varona Frolov, Serguei R; Acosta Silva, Marcela P; Volo Pérez, Guido; Fiuza Pérez, Maria D

2015-11-01

Acute aortic occlusion (AAO) is a rare disease with high morbidity and mortality. The aim of this study was to describe the results of surgical treatment of acute aortic occlusion and risk factors for mortality. Retrospective review of the clinical history of 29 patients diagnosed and operated on for AAO during 28 years. The following variables were analysed: age, sex, tabaco use, diabetes, chronic renal insufficiency, chronic heart failure, atrial fibrillation, arterial hypertension, symptoms, diagnosis and treatment, 30-day mortality and long-term survival. A univariant analysis was performed of variables related to mortality. Twenty-nine patients were included (18 male) with a mean age of 66,2 years. The aetiology was: embolism (EM) in 11 cases and Thrombosis (TR) in 18 cases. The surgical procedures performed included bilateral transfemoral thrombectomy (14 cases), aorto-bifemoral by-pass (8 cases), axilo uni/bifemoral by-pass (5 cases) and aortoiliac and renal tromboendarterectomy (2 cases). Morbidity included: renal failure (14 cases), mesenteric ischemia (4 cases), cardiac complications (7 cases), respiratory complications (5 cases) and loss of extremity (2 cases). The in-hospital mortality was 21% (EM 0%, TR 21%). The estimated survival at 1.3 and 5 years was 60, 50 and 44% respectively. Age (p=0.032), arterial hypertension (p=0.039) and aetiology of the AAO (p=0.039) were related to mortality. Acute aortic occlusion is a medical emergency with high mortality rates. Acute renal failure is the most common postoperative complication. Copyright © 2012 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine.

PubMed

Lipton, Richard B; Fanning, Kristina M; Serrano, Daniel; Reed, Michael L; Cady, Roger; Buse, Dawn C

2015-02-17

To test the hypothesis that ineffective acute treatment of episodic migraine (EM) is associated with an increased risk for the subsequent onset of chronic migraine (CM). In the American Migraine Prevalence and Prevention Study, respondents with EM in 2006 who completed the Migraine Treatment Optimization Questionnaire (mTOQ-4) and provided outcome data in 2007 were eligible for analyses. The mTOQ-4 is a validated questionnaire that assesses treatment efficacy based on 4 aspects of response to acute treatment. Total mTOQ-4 scores were used to define categories of acute treatment response: very poor, poor, moderate, and maximum treatment efficacy. Logistic regression models were used to examine the dichotomous outcome of transition from EM in 2006 to CM in 2007 as a function of mTOQ-4 category, adjusting for covariates. Among 5,681 eligible study respondents with EM in 2006, 3.1% progressed to CM in 2007. Only 1.9% of the group with maximum treatment efficacy developed CM. Rates of new-onset CM increased in the moderate treatment efficacy (2.7%), poor treatment efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. In the fully adjusted model, the very poor treatment efficacy group had a more than 2-fold increased risk of new-onset CM (odds ratio = 2.55, 95% confidence interval 1.42-4.61) compared to the maximum treatment efficacy group. Inadequate acute treatment efficacy was associated with an increased risk of new-onset CM over the course of 1 year. Improving acute treatment outcomes might prevent new-onset CM, although reverse causality cannot be excluded. © 2015 American Academy of Neurology.

Guidelines for the treatment of acute ischaemic stroke.

PubMed

Alonso de Leciñana, M; Egido, J A; Casado, I; Ribó, M; Dávalos, A; Masjuan, J; Caniego, J L; Martínez Vila, E; Díez Tejedor, E; Fuentes, B; Álvarez-Sabin, J; Arenillas, J; Calleja, S; Castellanos, M; Castillo, J; Díaz-Otero, F; López-Fernández, J C; Freijo, M; Gállego, J; García-Pastor, A; Gil-Núñez, A; Gilo, F; Irimia, P; Lago, A; Maestre, J; Martí-Fábregas, J; Martínez-Sánchez, P; Molina, C; Morales, A; Nombela, F; Purroy, F; Rodríguez-Yañez, M; Roquer, J; Rubio, F; Segura, T; Serena, J; Simal, P; Tejada, J; Vivancos, J

2014-03-01

Update of Acute Ischaemic Stroke Treatment Guidelines of the Spanish Neurological Society based on a critical review of the literature. Recommendations are made based on levels of evidence from published data and studies. Organized systems of care should be implemented to ensure access to the optimal management of all acute stroke patients in stroke units. Standard of care should include treatment of blood pressure (should only be treated if values are over 185/105 mmHg), treatment of hyperglycaemia over 155 mg/dl, and treatment of body temperature with antipyretic drugs if it rises above 37.5 °C. Neurological and systemic complications must be prevented and promptly treated. Decompressive hemicraniectomy should be considered in cases of malignant cerebral oedema. Intravenous thrombolysis with rtPA should be administered within 4.5 hours from symptom onset, except when there are contraindications. Intra-arterial pharmacological thrombolysis can be considered within 6 hours, and mechanical thrombectomy within 8 hours from onset, for anterior circulation strokes, while a wider window of opportunity up to 12-24 hours is feasible for posterior strokes. There is not enough evidence to recommend routine use of the so called neuroprotective drugs. Anticoagulation should be administered to patients with cerebral vein thrombosis. Rehabilitation should be started as early as possible. Treatment of acute ischaemic stroke includes management of patients in stroke units. Systemic thrombolysis should be considered within 4.5 hours from symptom onset. Intra-arterial approaches with a wider window of opportunity can be an option in certain cases. Protective and restorative therapies are being investigated. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Predictors of mental health-related acute service utilisation and treatment costs in the 12 months following an acute psychiatric admission.

PubMed

Siskind, Dan; Harris, Meredith; Diminic, Sandra; Carstensen, Georgia; Robinson, Gail; Whiteford, Harvey

2014-11-01

A key step in informing mental health resource allocation is to identify the predictors of service utilisation and costs. This project aims to identify the predictors of mental health-related acute service utilisation and treatment costs in the year following an acute public psychiatric hospital admission. A dataset containing administrative and routinely measured outcome data for 1 year before and after an acute psychiatric admission for 1757 public mental health patients was analysed. Multivariate regression models were developed to identify patient- and treatment-related predictors of four measures of service utilisation or cost: (a) duration of index admission; and, in the year after discharge from the index admission (b) acute psychiatric inpatient bed-days; (c) emergency department (ED) presentations; and (d) total acute mental health service costs. Split-sample cross-validation was used. A diagnosis of psychosis, problems with living conditions and prior acute psychiatric inpatient bed-days predicted a longer duration of index admission, while prior ED presentations and self-harm predicted a shorter duration. A greater number of acute psychiatric inpatient bed-days in the year post-discharge were predicted by psychosis diagnosis, problems with living conditions and prior acute psychiatric inpatient admissions. The number of future ED presentations was predicted by past ED presentations. For total acute care costs, diagnosis of psychosis was the strongest predictor. Illness acuity and prior acute psychiatric inpatient admission also predicted higher costs, while self-harm predicted lower costs. The development of effective models for predicting acute mental health treatment costs using existing administrative data is an essential step towards a workable activity-based funding model for mental health. Future studies would benefit from the inclusion of a wider range of variables, including ethnicity, clinical complexity, cognition, mental health legal status

Treatment Option Overview (Adult Acute Myeloid Leukemia)

MedlinePlus

... in the past. Having had treatment for childhood acute lymphoblastic leukemia (ALL) in the past. Being exposed to radiation from an atomic bomb or to the chemical benzene . Having a history of a blood disorder such as myelodysplastic syndrome . Signs and symptoms of adult AML include fever, ...

Treatment Options for Adult Acute Myeloid Leukemia

MedlinePlus

... in the past. Having had treatment for childhood acute lymphoblastic leukemia (ALL) in the past. Being exposed to radiation from an atomic bomb or to the chemical benzene . Having a history of a blood disorder such as myelodysplastic syndrome . Signs and symptoms of adult AML include fever, ...

[Drug treatment of acute myelogenous leukaemia. Current options and future perspectives].

PubMed

Telek, Béla; Rejtő, László; Batár, Péter; Miltényi, Zsófia; Reményi, Gyula; Simon, Zsófia; Ujj, Zsófia; Mezei, Gabriella; Szász, Róbert; Kiss, Attila; Udvardy, Miklós; Illés, Árpád

2016-05-29

Acute myelogenous leukemia is a heterogeneous disease. Recent molecular mutational analysis techniques have shed more light on different, genetically well characterised types of the disease. Treatment approach is uniform except for acute promyelocytic leukemia. Application of the "3 + 7" induction treatment has been the gold standard in the past 40 years. While the dose of cytarabine has not been changed, escalating daunorubicine dose in younger (<60 years) patients with good performance status to 90 mg/m(2) had a positive impact on overall survival. High dose chemotherapy is tolerated poorly in patients older than 60 years of age and, as treatment is not curative in the elderly, improvement of overall survival and quality of life remains the main goal of management in these patients. Low intensity treatment is beneficial and can provide additional advantage over supportive care. Innovative and targeted therapy approaches might give promise to better management of patients with acute myelogenous leukemia.

[Current treatment options in acute myeloid leukemia].

PubMed

Heuser, M; Schlenk, R F; Ganser, A

2011-12-01

Genetic aberrations form the basis for diagnostic classification of patients with acute myeloid leukemia (AML) according to the World Health Organization (WHO) classification. Moreover, these aberrations predict response to induction chemotherapy, relapse-free survival, and overall survival of patients with AML. Understanding the pathogenetic role of cytogenetic and molecular changes has led to the development of targeted treatment strategies that require rapid diagnostic assessment of the genetic profile of each patient to select the best treatment available.

Group vs. Individual Treatment for Acute Insomnia: A Pilot Study Evaluating a "One-Shot" Treatment Strategy.

PubMed

Boullin, Pam; Ellwood, Christina; Ellis, Jason G

2016-12-23

Despite undeniable evidence for the efficacy and effectiveness of Cognitive Behaviour Therapy for Insomnia (CBT-I), the potential for its widespread dissemination and implementation has yet to be realised. A suggested reason for this is that traditional CBT-I is considered too burdensome for deployment, in its current form, within the context of where it would be most beneficial-Primary Care. One strategy, aimed to address this, has been to develop briefer versions of CBT-I, whilst another has been to deliver CBT-I in a group format. An alternative has been to attempt to address insomnia during its acute phase with a view to circumventing its progression to chronic insomnia. The aim of the present study was to compare a brief version of CBT-I (one-shot) when delivered individually or in groups to those with acute insomnia. Twenty-eight individuals with acute insomnia (i.e., meeting full DSM-5 criteria for insomnia disorder for less than three months) self-assigned to either a group or individual treatment arm. Treatment consisted of a single one-hour session accompanied by a self-help pamphlet. Subjects completed measures of insomnia severity, anxiety and depression pre-treatment and at one-month post-treatment. Additionally, daily sleep diaries were compared between pre-treatment and at the one-month follow up. There were no significant between group differences in treatment outcome on any sleep or mood measures although those in the group treatment arm were less adherent than those who received individual treatment. Furthermore, the combined (group and individual treatment arms) pre-post test effect size on insomnia symptoms, using the Insomnia Severity Index, was large ( d = 2.27). It appears that group treatment is as efficacious as individual treatment within the context of a "one shot" intervention for individuals with acute insomnia. The results are discussed with a view to integrating one-shot CBT-I in Primary Care.

DoD–NCCAM/NIH Workshop on Acupuncture for Treatment of Acute Pain

PubMed Central

Belard, Jean Louis; Glowa, John; Khalsa, Partap; Weber, Wendy; Huntley, Kristen

2013-01-01

Abstract The Department of Defense (DoD) and the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH) cosponsored a workshop that explored the possible benefits of acupuncture treatment for acute pain. One goal of the workshop was to establish a roadmap to building an evidence base on that would indicate whether acupuncture is helpful for treating active-duty military personnel experiencing acute pain. The workshop highlighted brief presentations on the most current research on acupuncture and acute pain mechanisms. The impact of various modifiers (stress, genetics, population, phenotypes, etc.) on acute pain pathways and response to acupuncture treatment was discussed. Additional presentations focused on common neural mechanisms, an overview of real-world experience with using acupuncture to treat traumatic acute pain, and best tools and methods specific for acupuncture studies. Three breakout groups addressed the gaps, opportunities, and barriers to acupuncture use for acute pain in military and trauma settings. Different models of effectiveness research and optimal research designs for conducting trials in acute traumatic pain were also discussed. PMID:23020611

Adult Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Acute myeloid (myelogenous) leukemia (AML) treatment options include chemotherapy, radiation therapy, stem cell transplant, and other medications. Cytogenetic analysis helps predict treatment outcomes. Get detailed information about AML in this summary for clinicians.

Acute Fluoxetine Treatment Induces Slow Rolling of Leukocytes on Endothelium in Mice

PubMed Central

Herr, Nadine; Mauler, Maximilian; Witsch, Thilo; Stallmann, Daniela; Schmitt, Stefanie; Mezger, Julius; Bode, Christoph; Duerschmied, Daniel

2014-01-01

Objective Activated platelets release serotonin at sites of inflammation where it acts as inflammatory mediator and enhances recruitment of neutrophils. Chronic treatment with selective serotonin reuptake inhibitors (SSRI) depletes the serotonin storage pool in platelets, leading to reduced leukocyte recruitment in murine experiments. Here, we examined the direct and acute effects of SSRI on leukocyte recruitment in murine peritonitis. Methods C57Bl/6 and Tph1−/− (Tryptophan hydroxylase1) mice underwent acute treatment with the SSRI fluoxetine or vehicle. Serotonin concentrations were measured by ELISA. Leukocyte rolling and adhesion on endothelium was analyzed by intravital microscopy in mesentery venules with and without lipopolysaccharide challenge. Leukocyte extravasation in sterile peritonitis was measured by flow cytometry of abdominal lavage fluid. Results Plasma serotonin levels were elevated 2 hours after fluoxetine treatment (0.70±0.1 µg/ml versus 0.27±0.1, p = 0.03, n = 14), while serum serotonin did not change. Without further stimulation, acute fluoxetine treatment increased the number of rolling leukocytes (63±8 versus 165±17/0.04 mm2min−1) and decreased their velocity (61±6 versus 28±1 µm/s, both p<0.0001, n = 10). In Tph1−/− mice leukocyte rolling was not significantly influenced by acute fluoxetine treatment. Stimulation with lipopolysaccharide decreased rolling velocity and induced leukocyte adhesion, which was enhanced after fluoxetine pretreatment (27±3 versus 36±2/0.04 mm2, p = 0.008, n = 10). Leukocyte extravasation in sterile peritonitis, however, was not affected by acute fluoxetine treatment. Conclusions Acute fluoxetine treatment increased plasma serotonin concentrations and promoted leukocyte-endothelial interactions in-vivo, suggesting that serotonin is a promoter of acute inflammation. E-selectin was upregulated on endothelial cells in the presence of serotonin, possibly explaining the observed

Microbiology and Treatment of Acute Apical Abscesses

PubMed Central

Rôças, Isabela N.

2013-01-01

SUMMARY Acute apical abscess is the most common form of dental abscess and is caused by infection of the root canal of the tooth. It is usually localized intraorally, but in some cases the apical abscess may spread and result in severe complications or even mortality. The reasons why dental root canal infections can become symptomatic and evolve to severe spreading and sometimes life-threatening abscesses remain elusive. Studies using culture and advanced molecular microbiology methods for microbial identification in apical abscesses have demonstrated a multispecies community conspicuously dominated by anaerobic bacteria. Species/phylotypes commonly found in these infections belong to the genera Fusobacterium, Parvimonas, Prevotella, Porphyromonas, Dialister, Streptococcus, and Treponema. Advances in DNA sequencing technologies and computational biology have substantially enhanced the knowledge of the microbiota associated with acute apical abscesses and shed some light on the etiopathogeny of this disease. Species richness and abundance and the resulting network of interactions among community members may affect the collective pathogenicity and contribute to the development of acute infections. Disease modifiers, including transient or permanent host-related factors, may also influence the development and severity of acute abscesses. This review focuses on the current evidence about the etiology and treatment of acute apical abscesses and how the process is influenced by host-related factors and proposes future directions in research, diagnosis, and therapeutic approaches to deal with this disease. PMID:23554416

Plasma BDNFs level initially and post treatment in acute mania: comparison between ECT and atypical antipsychotic treatment and healthy controls.

PubMed

Karamustafalioglu, Nesrin; Genc, Abdullah; Kalelioglu, Tevfik; Tasdemir, Akif; Umut, Gokhan; Incir, Said; Akkuş, Mustafa; Emul, Murat

2015-08-01

Inconsistent findings concerning brain-derived neurotrophic factor (BDNF) levels across different episodes in bipolar disorder have been reported, which is also in line with the treatment effects on BDNF levels in acute mania. We aimed to compare plasma BDNF level alterations after pure antipsychotic drug or ECT plus antipsychotic drug treatment in acute mania. Sixty-eight patients with mania were divided into two treatment arms: the antipsychotic treatment arm (AP) and electroconvulsive therapy (ECT)+AP arm. In addition, 30 healthy controls were included in the study. There was no significant statistical difference according to mean age, education level, marital and working status between patients and healthy controls. The initial serum BDNF level in patients with acute mania was significantly lower than healthy controls. The initial BDNF level between the ECT arm and AP arm was not significant. The BDNF level decreased significantly after reaching remission in patients with acute mania. The change in BDNF level in the AP arm was not significant while in the ECT arm it was significant after treatment. In this study, for the first time we revealed a significant decrease in BDNF levels after ECT sessions in acute manic patients. Besides clinical remission after treatment in acute mania, the decrement in BDNF levels does not seem to be related to clinical response. Thus cumulative effects of mood episodes for the ongoing decrease in BDNF levels might be borne in mind despite the achievement of remission and/or more time being required for an increase in BDNF levels after treatment. © The Author(s) 2015.

Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult acute lymphoblastic leukemia (ALL) treatment options include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Get detailed information about the molecular genetics, prognosis, and treatment of ALL in this summary for clinicians.

Oral antivirals for the acute treatment of recurrent herpes labialis.

PubMed

Jensen, Lori A; Hoehns, James D; Squires, Cindy L

2004-04-01

To evaluate the use and benefit of oral antivirals in the acute treatment of episodic, recurrent herpes labialis. A literature search was performed in MEDLINE (1966-August 2003) using acyclovir, famciclovir, valacyclovir, cold sores, herpes labialis, and HSV-1 as search terms. We reviewed 5 placebo-controlled and 2 comparative studies evaluating oral antivirals for acute treatment of recurrent herpes labialis. No studies directly compared different antivirals. Studies discussing the efficacy of antivirals for chronic suppression of herpes simplex virus-1 infection were not included. Treatment with oral antivirals decreases the duration of lesion episodes and pain by approximately one day; however, the antivirals do not abort lesions from developing. Clinical implications of these results appear relatively modest.

Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline reverses the neurotoxic effects of the prion protein fragment 90-231.

PubMed

Corsaro, Alessandro; Thellung, Stefano; Chiovitti, Katia; Villa, Valentina; Simi, Alessandro; Raggi, Federica; Paludi, Domenico; Russo, Claudio; Aceto, Antonio; Florio, Tullio

2009-02-01

Several in vitro and in vivo studies addressed the identification of molecular determinants of the neuronal death induced by PrP(Sc) or related peptides. We developed an experimental model to assess PrP(Sc) neurotoxicity using a recombinant polypeptide encompassing amino acids 90-231 of human PrP (hPrP90-231) that corresponds to the protease-resistant core of PrP(Sc) identified in prion-infected brains. By means of mild thermal denaturation, we can convert hPrP90-231 from a PrP(C)-like conformation into a PrP(Sc)-like structure. In virtue of these structural changes, hPrP90-231 powerfully affected the survival of SH-SY5Y cells, inducing caspase 3 and p38-dependent apoptosis, while in the native alpha-helix-rich conformation, hPrP90-231 did not induce cell toxicity. The aim of this study was to identify drugs able to block hPrP90-231 neurotoxic effects, focusing on minocycline, a tetracycline with known neuroprotective activity. hPrP90-231 caused a caspase 3-dependent apoptosis via the blockade of ERK1/2 activation and the subsequent activation of p38 MAP kinase. We propose that hPrP90-231-induced apoptosis is dependent on the inhibition of ERK1/2 responsiveness to neurotrophic factors, removing a tonic inhibition of p38 activity and resulting in caspase 3 activation. Minocycline prevented hPrP90-231-induced toxicity interfering with this mechanism: the pretreatment with this tetracycline restored ERK1/2 activity and reverted p38 and caspase 3 activities. The effects of minocycline were not mediated by the prevention of hPrP90-231 structural changes or cell internalization (differently from Congo Red). In conclusion, minocycline elicits anti-apoptotic effects against the neurotoxic activity of hPrP90-231 and these effects are mediated by opposite modulation of ERK1/2 and p38 MAP kinase activities.

Maternal depressive symptoms in pediatric major depressive disorder: relationship to acute treatment outcome.

PubMed

Kennard, Betsy D; Hughes, Jennifer L; Stewart, Sunita M; Mayes, Taryn; Nightingale-Teresi, Jeanne; Tao, Rongrong; Carmody, Thomas; Emslie, Graham J

2008-06-01

In the present study, we assess maternal depressive symptoms at the beginning and end of treatment to investigate the possible reciprocal relationship of maternal illness with the child's depressive illness and treatment. We present data on 146 children and their mothers who were participating in a pediatric acute treatment study of fluoxetine. Patients were assessed with the Children's Depression Rating Scale-Revised at baseline and at each treatment visit. Mothers completed the Quick Inventory of Depressive Symptomatology-Self Report at baseline and end of acute treatment. Thirty percent of mothers had moderate to severe levels of depressive symptoms at the child's baseline assessment. Overall, mothers reported improvement in maternal depressive symptoms at the end of their child's acute treatment, although maternal depression was not specifically targeted for intervention. Furthermore, mother's depressive symptoms appear to be associated with the child's depression severity both at the beginning and end of treatment. Mothers with higher levels of depressive symptoms had children with higher levels of depression severity at baseline and over the course of treatment. However, maternal depressive symptoms at baseline had no association with the rate of improvement of child depression severity. This study indicates a positive relationship between the depression severity of mothers and their children. These findings highlight potential areas of intervention in the acute treatment of childhood depression.

[Cost effectiveness in treatment of acute myeloid leukemia].

PubMed

Nordmann, P; Schaffner, A; Dazzi, H

2000-12-23

Although the rise in health costs is a widely debated issue, in Switzerland it was until recently taken for granted that patients are given the best available treatment regardless of cost. An example of a disease requiring costly treatment is acute myelogenous leukaemia (AML). To relate cost to benefit we calculated expenditure per life years gained. To assess costs we determined the real cost of treatment up to total remission, followed by consolidation or withdrawal of treatment or death. For survival time exceeding the 2-year observation period we used data from recent literature. The average cost of treatment ranges up to 107,592 Swiss francs (CHF). In 1997 we treated 23 leukaemia patients at Zurich University Hospital and gained a total of 210 life years. This represents an average cost of CHF 11,741 per life year gained. Chief cost items were therapy and personnel costs for nursing staff, followed by hotel business and personnel costs for doctors and diagnosis. Our results for AML treatment are far removed from the $61,500 ranging up to $166,000 discussed in the literature as the "critical" QALY (quality adjusted life years) value. This is the first time the actual costs of AML therapy have been shown for a Swiss cohort. Despite high initial treatment costs and success only in a limited number of patients, the expenditure per QALY is surprisingly low and shows clearly the effectiveness of apparently costly acute medicine.

Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment.

PubMed

Cernan, Martin; Szotkowski, Tomas; Pikalova, Zuzana

2017-09-01

Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic malignancies in which blasts show markers of multiple developmental lineages and cannot be clearly classified as acute myeloid or lymphoblastic leukemias. Historically, various names and classifications were used for this rare entity accounting for 2-5% of all acute leukemias depending on the diagnostic criterias used. The currently valid classification of myeloid neoplasms and acute leukemia published by the World Health Organization (WHO) in 2016 refers to this group of diseases as MPAL. Because adverse cytogenetic abnormalities are frequently present, MPAL is generally considered a disease with a poor prognosis. Knowledge of its treatment is limited to retrospective analyses of small patient cohorts. So far, no treatment recommendations verified by prospective studies have been published. The reported data suggest that induction therapy for acute lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation is more effective than induction therapy for acute myeloid leukemia or consolidation chemotherapy. The establishment of cooperative groups and international registries based on the recent WHO criterias are required to ensure further progress in understanding and treatment of MPAL. This review summarizes current knowledge on the diagnosis, classification, prognosis and treatment of MPAL patients.

Monitoring and treatment of acute gastrointestinal bleeding.

PubMed

Lenjani, Basri; Zeka, Sadik; Krasniqi, Salih; Bunjaku, Ilaz; Jakupi, Arianit; Elshani, Besni; Xhafa, Agim

2012-01-01

Acute gastrointestinal bleeding-massive acute bleeding from gastrointestinal section is one of the most frequent forms of acute abdomen. The mortality degree in emergency surgery is about 10%. It's very difficult to identify the place of bleeding and etiology. The important purpose of this research is to present the cases of acute gastrointestinal bleeding from the patients which were monitored and treated at The University Clinical Center of Kosova-Emergency Center in Pristina. These inquests included 137 patients with acute gastrointestinal bleeding who were treated in emergency center of The University Clinical Center in Pristina for the period from January 2005 until December 2006. From 137 patients with acute gastrointestinal bleeding 41% or 29% was female and 96% or 70.1% male. Following the sex we gained a high significant difference of statistics (p < 0.01). The gastrointestinal bleeding was two times more frequent in male than in female. Also in the age-group we had a high significant difference of statistics (p < 0.01) 63.5% of patients were over 55 years old. The mean age of patients with an acute gastrointestinal bleeding was 58.4 years SD 15.8 age. The mean age for female patients was 56.4 age SD 18.5 age. The patients with arterial systolic pressure under 100 mmHg have been classified as patients with hypovolemic shock. They participate with 17.5% in all prevalence of acute gastrointestinal bleeding. From the number of prevalence 2 {1.5%} patients have been diagnosed with peptic ulcer, 1 {0.7%} as gastric perforation and 1 {0.7%} with intestine ischemia. Abdominal Surgery and Intensive Care 2 or 1.5% died, 1 at intensive care unit and 1 at nephrology. As we know the severe condition of the patients with gastrointestinal bleeding and etiology it is very difficult to establish, we need to improve for the better conditions in our emergency center for treatment and initiation base of clinic criteria.

Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Acute myeloid leukemia (AML), juvenile myelomonocytic leukemia (JMML), acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) account for about 20% of childhood myeloid leukemias. Other myeloid malignancies include transient abnormal myelopoiesis and myelodysplastic syndrome. Get detailed information about the classification, clinical presentation, diagnostic and molecular evaluation, prognosis, and treatment of newly diagnosed and recurrent disease in this summary for clinicians.

[Usefulness of fenspiride in the treatment of acute otitis media in children].

PubMed

Zielnik-Jurkiewicz, Beata; Jurkiewicz, Dariusz

2005-06-01

Acute otitis media is very general disease and concerns every child practically. The shortening the time of treatment as well as quick decrease of symptoms, and mainly the pain have large meaning in treatment of this disease. Combined treatment of fenspiride and typical treatment of otitis media permits as our investigations show on quicker and observed at children's larger number decrease of symptoms in children with acute otitis media. The aim of the study was to observe effectiveness of combined treatment with antibiotic and fenspiride in children with acute otitis media. The study comprised 40 children (mean age 8.2 years). The diagnosis of acute otitis media based on medical history data, otolaryngological examination and audiometry (tone and impedance). Children with GERD, hypersensitivity to amoxicillin and fenspiride as well as hypertrophy of adenoid were excluded from the study. Children were divided in two equal groups randomly. All children received amoxicillin in dose 80 mg/kg/day in three partite doses (Amotaks, Polfa Tarchomin Poland) as well as oxymethazolin 0.05% nasal drops 3 x day 1-2 drops (0.05% Nasivin, Merck Germany). In children from second group fenspiride was applied in dose 2 ml/kg/day in three divided doses (Eurespal, Servier Francja) additionally. Treatment was provided by 10 days. During the treatment parents made record of recession in 10 point scale, estimating following parameters: the pain of ear, bother, raised the temperature of body, loss of appetite, vomiting, diarrhea, otorrhea and crying. After end of treatment control otolaryngological and audiological examinations were performed. In studied children symptoms were similar, and the pain of ear was in both groups main suffering. Vomiting and diarrhea the most seldom were observed. In children with acute otitis media treated additionally with fenspiride statistically significant (p<0.01) quicker recession of clinical symptoms was observed. Statistically significant (p<0

Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome

PubMed Central

Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

2014-01-01

Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress. PMID:24932421

BET 2: LASER THERAPY IN THE TREATMENT OF ACUTE HAMSTRING MUSCLE INJURIES.

PubMed

Hughes, Tom; Callaghan, Michael

2017-04-01

Local laser therapy has been suggested as a promising treatment for acute hamstring muscle tears. We carried out a shortcut systematic review to establish whether therapeutic lasers are beneficial for patients with acute hamstring tears. Despite a comprehensive literature search, no studies that were directly relevant to the question could be identified. The clinical bottom line is therefore that there is currently no evidence for the use of any form of laser therapy in the treatment of acute hamstring muscle tears. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

MRI-Guided Selection of Patients for Acute Ischemic Stroke Treatment

PubMed Central

Leigh, Richard; Krakauer, John W.

2014-01-01

Purpose of review To summarize what is known about the use of MRI in acute stroke treatments (predominantly thrombolysis), to examine the assumptions and theories behind the interpretation of MR images of acute stroke and how they are used to select patients for therapies, and to suggest directions for future research. Recent findings Recent studies have been contradictory about the usefulness of MRI in selecting patients for treatment. New MRI models for selecting patients have emerged that focus not only on the ischemic penumbra but also the core infarct. Fixed time-window selection parameters are being replaced by individualized MRI features. New ways to interpret traditional MRI sequences are emerging. Summary Although the efficacy of acute stroke treatment is time dependent, the use of fixed time-windows does not account for individual differences in infarct evolution, which could be detected with MRI. While MRI shows promise for identifying patients who should be treated, as well as exclude patients who should not be treated, definitive evidence is still lacking. Future research should focus on validating the use of MRI to select patients for IV therapies in extended time windows. PMID:24978637

Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

ERIC Educational Resources Information Center

Janzen, Laura A.; Spiegler, Brenda J.

2008-01-01

This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

Childhood Acute Myeloid Leukemia Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood acute myeloid leukemia and other myeloid malignancies treatment may include chemotherapy, radiation therapy, stem cell transplant, and targeted therapy. Learn more about AML and myelodysplastic/myeloproliferative diseases in this expert-reviewed summary.

Treatment of acute Achilles tendon ruptures in Central Finland Central Hospital in 2010-2015.

PubMed

Reito, Aleksi; Logren, Hanna-Liina; Ahonen, Katri; Nurmi, Heikki; Paloneva, Juha

The epidemiology of Achilles tendon ruptures and treatment strategies have undergone a major change in recent years. We investigated the incidence of acute Achilles tendon ruptures, the choice of treatment strategies and treatment implementation. The research material consisted of patients living in the catchment area of Central Finland Hospital District who had been diagnosed with an acute Achilles tendon rupture between 2010 and 2015. The final sample consisted of 266 patients. Conservative treatment was started for 207 patients, and the remaining 59 were referred for surgery. During the study period, the proportion of patients undergoing surgery fell from 41% to 10%. Three patients (1.4%) were referred for surgery during conservative treatment, and 10 patients (4.7%) developed deep vein thrombosis while wearing a cast or an orthosis. Twelve patients (5.8%) sustained a re-rupture after conservative treatment. Two surgically-treated patients (3.5%) sustained a re-rupture, and one patient (1.7%) developed deep vein thrombosis. The strategies for treating acute Achilles tendon ruptures have clearly become more conservative in our hospital. Conservative treatment is safe and rarely fails. However, it is important to bear in mind that surgery still has a role in the treatment of acute Achilles tendon ruptures.

77 FR 60126 - Guidance for Industry on Acute Bacterial Otitis Media: Developing Drugs for Treatment; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-02

...; Formerly Docket FDA-2008-N-0041; Formerly 2008N-0004] Guidance for Industry on Acute Bacterial Otitis Media... entitled ``Acute Bacterial Otitis Media: Developing Drugs for Treatment.'' This guidance addresses FDA's... an indication for the treatment of acute bacterial otitis media (ABOM). This guidance finalizes the...

[The administration of homeopathic drugs for the treatment of acute mastitis in cattle].

PubMed

Merck, C C; Sonnenwald, B; Rollwage, H

1989-08-01

The general principles of homeopathic therapy are described together with a number of homeopathic drugs used for the treatment of acute bovine mastitis. Fifty cows with acute mastitis were used in the study. The initial treatment comprised aconitum D 4, phytolacca D 1 and bryonia D 4. In subsequent treatments phytolacca D 1, bryonia D 4 and lachesis D 8 either singly or in combination were used; mercurius solubilis D 4 was also used. Encouraging results, especially in the treatment of cases of E.coli mastitis, were achieved.

Is Customization in Antidepressant Prescribing Associated with Acute-Phase Treatment Adherence?

PubMed

Merrick, Elizabeth L; Hodgkin, Dominic; Panas, Lee; Soumerai, Stephen B; Ritter, Grant

2012-03-01

OBJECTIVES: The objective was to explore whether prescribing variation is associated with duration of antidepressant use during the acute phase of treatment. Improving quality of care and increasing the extent to which treatment is patient-centered and customized are interrelated goals. Prescribing variation may be considered a marker of customization, and could be associated with better antidepressant treatment adherence. METHODS: A cross-sectional secondary data analysis examining the association between providers' antidepressant prescribing variation and patient continuity of antidepressant treatment. The data source was two states' Medicaid claims for dual-eligible Medicaid/Medicare patients. The sample included 383 patients with new episodes of antidepressant treatment, representing 70 providers with at least four patients in the sample. We tested two alternate measures of prescribing concentration: 1) share of prescriber's initial antidepressant prescribing accounted for by the two most common regimens, and 2) Herfindahl index. The HEDIS performance measure of effective acute-phase treatment (at least 84 out of 114 days with antidepressant) was the dependent variable. KEY FINDINGS: In multivariate analyses, the concentration measure based on the top two regimens was significant and inversely related to duration adequacy (p <.05). The Herfindahl index measure showed a trend towards a similar inverse relationship (p<.10). CONCLUSIONS: The findings provide some support for the hypothesized relationship between prescribing variation and adequate antidepressant treatment duration during the acute phase of treatment. Future work with more detailed, clinical longitudinal data could extend this inquiry to better understand the causal mechanisms using a more direct measure of customized care.

Is Customization in Antidepressant Prescribing Associated with Acute-Phase Treatment Adherence?

PubMed Central

Merrick, Elizabeth L.; Hodgkin, Dominic; Panas, Lee; Soumerai, Stephen B.; Ritter, Grant

2012-01-01

Objectives The objective was to explore whether prescribing variation is associated with duration of antidepressant use during the acute phase of treatment. Improving quality of care and increasing the extent to which treatment is patient-centered and customized are interrelated goals. Prescribing variation may be considered a marker of customization, and could be associated with better antidepressant treatment adherence. Methods A cross-sectional secondary data analysis examining the association between providers' antidepressant prescribing variation and patient continuity of antidepressant treatment. The data source was two states' Medicaid claims for dual-eligible Medicaid/Medicare patients. The sample included 383 patients with new episodes of antidepressant treatment, representing 70 providers with at least four patients in the sample. We tested two alternate measures of prescribing concentration: 1) share of prescriber's initial antidepressant prescribing accounted for by the two most common regimens, and 2) Herfindahl index. The HEDIS performance measure of effective acute-phase treatment (at least 84 out of 114 days with antidepressant) was the dependent variable. Key Findings In multivariate analyses, the concentration measure based on the top two regimens was significant and inversely related to duration adequacy (p <.05). The Herfindahl index measure showed a trend towards a similar inverse relationship (p<.10). Conclusions The findings provide some support for the hypothesized relationship between prescribing variation and adequate antidepressant treatment duration during the acute phase of treatment. Future work with more detailed, clinical longitudinal data could extend this inquiry to better understand the causal mechanisms using a more direct measure of customized care. PMID:22707982

Pentoxifylline Treatment in Acute Pancreatitis (AP)

ClinicalTrials.gov

2018-02-21

Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

Comprehensive CT Evaluation in Acute Ischemic Stroke: Impact on Diagnosis and Treatment Decisions

PubMed Central

Löve, Askell; Siemund, Roger; Andsberg, Gunnar; Cronqvist, Mats; Holtås, Stig; Björkman-Burtscher, Isabella

2011-01-01

Background. With modern CT imaging a comprehensive overview of cerebral macro- and microcirculation can be obtained within minutes in acute ischemic stroke. This opens for patient stratification and individualized treatment. Methods. Four patients with acute ischemic stroke of different aetiologies and/or treatments were chosen for illustration of the comprehensive CT protocol and its value in subsequent treatment decisions. The patients were clinically evaluated according to the NIHSS-scale, examined with the comprehensive CT protocol including both CT angiography and CT perfusion, and followed up by MRI. Results. The comprehensive CT examination protocol increased the examination time but did not delay treatment initiation. In some cases CT angiography revealed the cause of stroke while CT perfusion located and graded the perfusion defect with reasonable accuracy, confirmed by follow-up MR-diffusion. In the presented cases findings of the comprehensive CT examination influenced the treatment strategy. Conclusions. The comprehensive CT examination is a fast and safe method allowing accurate diagnosis and making way for individualized treatment in acute ischemic stroke. PMID:21603175

Acute torn meniscus combined with acute cruciate ligament injury. Second look arthroscopy after 3-month conservative treatment.

PubMed

Ihara, H; Miwa, M; Takayanagi, K; Nakayama, A

1994-10-01

The purpose of this study was to evaluate arthroscopically the natural healing of an acute torn meniscus combined with an acute cruciate ligament injury treated nonoperatively. There were 30 lateral and 10 medial meniscus tears associated with 25 acute anterior cruciate ligament and 7 posterior cruciate ligament injuries in 32 patients. There was more than 1 tear on some menisci for a total of 51 tear sites. Injuries to the menisci and ligaments were allowed to heal without surgery, but were given protective mobilization immediately in order to stimulate stress oriented healing of injured collagen fibers and promote circulation of synovial fluid to the meniscus and ligament. A Kyuro knee brace with a coil spring traction system was used to add adequate but not excessive stress to the associated injured cruciate ligament. All knees were examined and arthroscoped before and after a 3-month treatment period. Results indicated that 69% of the lateral menisci healed completely and 18% healed partially, whereas 58% of the medial menisci healed completely and none healed partially. Twenty of 25 anterior cruciate ligaments and 3 of 7 posterior cruciate ligaments healed satisfactorily. This study indicated that acute tears of the meniscus, even when they occur in association with a cruciate ligament injury, can heal morphologically with nonsurgical treatment.

Recovery of calf muscle strength following acute achilles tendon rupture treatment: a comparison between minimally invasive surgery and conservative treatment.

PubMed

Metz, Roderik; van der Heijden, Geert J M G; Verleisdonk, Egbert-Jan M M; Tamminga, Rob; van der Werken, Christiaan

2009-10-01

The aim of this study was to measure the effect of treatment of acute Achilles tendon ruptures on calf muscle strength recovery. Eighty-three patients with acute Achilles tendon rupture were randomly allocated to either minimally invasive surgery with functional after-treatment or conservative treatment by functional bracing. Calf muscle strength using isokinetic testing was evaluated at 3 months and after 6 or more months posttreatment. To exclusively investigate the effect of treatment on outcome, the authors excluded patients with major complications from the analysis. In 31 of 39 patients in the surgical treatment group and 25 of 34 patients in the conservative treatment group, isokinetic strength tests were performed. In the analysis of differences in mean peak torque, no statistically significant differences were found between surgery and conservative treatment, except for plantar flexion strength at 90 degrees per second at the second measurement, favoring conservative treatment. After 8 to 10 months follow- up, loss of plantar flexion strength was still present in the injured leg in both treatment groups. In conclusion, isokinetic muscle strength testing did not detect a statistically significant difference between minimally invasive surgical treatment with functional after-treatment and conservative treatment by functional bracing of acute Achilles tendon ruptures.

Diagnosis and treatment of acute phlegmonous gastritis: A case report.

PubMed

Yang, Hongxin; Yan, Zhiqiang; Chen, Jiaju; Xie, Haitao; Wang, Haibin; Wang, Qian

2018-05-01

Acute phlegmonous gastritis (PG) is a rare and often fatal condition mainly characterized by severe bacterial infection of the gastric wall. Case reports of PG over the past century average about 1 per year. Early diagnosis and immediate treatment are crucial to achieve positive outcomes. A 47-year-old man was referred to our hospital because of abdominal pain, high fever, and vomiting for 4 days, with aggravation for 24 hours. Physical examination revealed epigastric abdominal pain, rebound pain, and abdominal wall tightness. Abdominal CT showed thickening of the stomach wall with edema and gas. On the basis of symptoms and CT imaging findings, the patient was diagnosed with acute PG. Antibiotic therapy and operation. The patient immediately underwent an operation after conservative treatment using antibiotics proved ineffective. The whole stomach was obviously swollen, and the anterior side and posterior wall of the stomach were nigrescent necrotic. Hence, total gastrectomy was performed followed by reconstruction (roux-en-y), and pus that accumulated in the stomach wall was cultured. At postoperative broad-spectrum antibiotic coverage, the patient finally recovered. Acute PG is a rare infection of the gastric wall especially after antibiotic treatment. Given the fast progression of this disease, early recognition and immediate action are crucial to achieve positive outcomes.

Acute Infection in Total Knee Arthroplasty: Diagnosis and Treatment

PubMed Central

Martínez-Pastor, Juan Carlos; Maculé-Beneyto, Francisco; Suso-Vergara, Santiago

2013-01-01

Infection is one of the most serious complications after total knee arthroplasty (TKA). The current incidence of prosthetic knee infection is 1-3%, depending on the series. For treatment and control to be more cost effective, multidisciplinary groups made up of professionals from different specialities who can work together to eradicate these kinds of infections need to be assembled. About the microbiology, Staphylococcus aureus and coagulase-negative staphylococcus were among the most frequent microorganisms involved (74%). Anamnesis and clinical examination are of primary importance in order to determine whether the problem may point to a possible acute septic complication. The first diagnosis may then be supported by increased CRP and ESR levels. The surgical treatment for a chronic prosthetic knee infection has been perfectly defined and standardized, and consists in a two-stage implant revision process. In contrast, the treatment for acute prosthetic knee infection is currently under debate. Considering the different surgical techniques that already exist, surgical debridement with conservation of the prosthesis and polythene revision appears to be an attractive option for both surgeon and patient, as it is less aggressive than the two-stage revision process and has lower initial costs. The different results obtained from this technique, along with prognosis factors and conclusions to keep in mind when it is indicated for an acute prosthetic infection, whether post-operative or haematogenous, will be analysed by the authors. PMID:23919094

[Necrotic acute pancreatitis in the intensive care unit: a comparison between conservative and surgical medical treatment].

PubMed

Milian J, William; Portugal S, José; Laynez Ch, Richard; Rodríguez A, Cesar; Targarona, Javier; Barreda C, Luis

2010-01-01

To determine the prognosis of patients with necrotic acute pancreatitis receiving medical and surgical treatments. The severe acute pancreatitis treatment is multidisciplinary and requires a daily evaluation of the patient that will allow to observe changes and apply therapy in due time. The treatment includes: Admission in the ICU, fluids, nutrition and antibiotics, as well as other life supports for high-risk patients. Thus, patients undergo conservative treatment or, if it is necessary, surgery. A retrospective study of patients with necrotic acute pancreatitis admitted to the ICU between January 2004 and August 2006. The patients with necrotic acute pancreatitis without signs of sepsis underwent a conservative medical treatment, while fine needle punction-aspiration was performed in all patients who were suffering from necrotic acute pancreatitis and persistent sepsis four weeks after their admission and after discarding and eradicating every non-pancreatic focus of infection. All Gram stain or culture positive patients underwent surgery immediately. Seventy patients with necrotic acute pancreatitis were included in the study. Thirty-six patients (51%) suffered acute pancreatitis with sterile necrosis and underwent a conservative treatment, while 34 patients (49%) developed acute pancreatic with infected necrosis and underwent surgery. The average age was 55.19 vs. 57.65 (p=0.57). The average amylase was 1421.74 vs. 1402.45. (p=0.96). The tomography severity index was 8.47 vs. 8.79 (p=0.36). The Apache II was 8.22 vs. 9 (p=0.46). The average number of failed organs was 0.39 vs. 0.68. (p=0.19). The ICU stay was 10.75 vs. 26.5 days (p<0.05) while the total hospital stay was 46.47 vs. 57.26 days (p<0.05). The mortality rate was (3/36) 8.3% vs. (9/34) 26.5% (p<0.05) for conservative medical treatment vs. surgical treatment, respectively. Between the first and the twelfth month the evaluated patients who attended consultation, after discharge, showed: pancreatic

Treatment of hyperglycaemia in patients with acute stroke.

PubMed

Castilla-Guerra, L; Fernández-Moreno, M C; Hewitt, J

2016-03-01

The proportion of diabetic patients who are hospitalised for stroke has been increasing in recent years, currently reaching almost a third of all cases of stroke. In addition, about half of patients with acute stroke present hyperglycaemia in the first hours of the stroke. Although hyperglycaemia in the acute phase of stroke is associated with a poor prognosis, its treatment is currently a topic of debate. There is no evidence that the adminstration of intravenous insulin to these patients offers benefits in terms of the evolution of the stroke. New studies in development, such as the SHINE study (Stroke Hyperglycemia Insulin Network Effort), may contribute to clarifying the role of intensive control of glycaemia during the acute phase of the stroke. Ultimately, patients who have presented with stroke should be screened for diabetes. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Acute toxicity and chemical evaluation of coking wastewater under biological and advanced physicochemical treatment processes.

PubMed

Dehua, Ma; Cong, Liu; Xiaobiao, Zhu; Rui, Liu; Lujun, Chen

2016-09-01

This study investigated the changes of toxic compounds in coking wastewater with biological treatment (anaerobic reactor, anoxic reactor and aerobic-membrane bioreactor, A1/A2/O-MBR) and advanced physicochemical treatment (Fenton oxidation and activated carbon adsorption) stages. As the biological treatment stages preceding, the inhibition effect of coking wastewater on the luminescence of Vibrio qinghaiensis sp. Nov. Q67 decreased. Toxic units (TU) of coking wastewater were removed by A1/A2/O-MBR treatment process, however approximately 30 % TU remained in the biologically treated effluent. There is a tendency that fewer and fewer residual organic compounds could exert equal acute toxicity during the biological treatment stages. Activated carbon adsorption further removed toxic pollutants of biologically treated effluent but the Fenton effluent increased acute toxicity. The composition of coking wastewater during the treatment was evaluated using the three-dimensional fluorescence spectra, gas chromatography-mass spectrometry (GC-MS). The organic compounds with high polarity were the main cause of acute toxicity in the coking wastewater. Aromatic protein-like matters in the coking wastewater with low biodegradability and high toxicity contributed mostly to the remaining acute toxicity of the biologically treated effluents. Chlorine generated from the oxidation process was responsible for the acute toxicity increase after Fenton oxidation. Therefore, the incorporation of appropriate advanced physicochemical treatment process, e.g., activated carbon adsorption, should be implemented following biological treatment processes to meet the stricter discharge standards and be safer to the environment.

Methicillin-resistant Staphylococcus aureus: clinical manifestations and antimicrobial therapy.

PubMed

Cunha, B A

2005-07-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a common skin coloniser and less commonly causes infection. MRSA colonisation should be contained by infection control measures and not treated. MRSA infections cause the same spectrum of infection as MSSA infections, i.e., skin/soft tissue infections, bone/joint infections, central IV line infections, and acute bacterial endocarditis (native valve/prosthetic valve). There is a discrepancy between in-vitro sensitivity and in-vivo effectiveness with MRSA. To treat MRSA infections, clinicians should select an MRSA drug with proven in-vivo effectiveness, i.e., daptomycin. Linezolid, quinupristin/dalfopristin, minocycline, or vancomycin, and not rely on in-vitro susceptibility data. For MRSA, doxycycline cannot be substituted for minocycline. Linezolid and minocycline are available for oral administration and both are also effective in treating MRSA CNS infections. Vancomycin is being used less due to side effects, (increasing MICs/resistance, VISA/VRSA), and increased VRE prevalence. The most potent anti-MRSA drug at the present time is daptomycin. Daptomycin is useful when rapid/effective therapy of MRSA bacteraemia/endocarditis is necessary. Daptomycin is also useful to treat persistent MRSA bacteraemias/MRSA treatment failures with other drugs, i.e., vancomycin. There is no difference in virulence between MSSA and MRSA infections if treatment is started early and with an agent that has in-vivo effectiveness.

Early definitive treatment rate as a quality indicator of care in acute gallstone pancreatitis.

PubMed

Green, R; Charman, S C; Palser, T

2017-11-01

Early definitive treatment (cholecystectomy or endoscopic sphincterotomy in the same admission or within 2 weeks after discharge) of gallstone disease after a biliary attack of acute pancreatitis is standard of care. This study investigated whether compliance with early definitive treatment for acute gallstone pancreatitis can be used as a care quality indicator for the condition. A retrospective cohort study was conducted using the Hospital Episode Statistics database. All emergency admissions to National Health Service hospitals in England with a first time diagnosis of acute gallstone pancreatitis in the financial years 2008, 2009 and 2010 were examined. Trends in early definitive treatment between hospital trusts were examined and patient morbidity outcomes were determined. During the study interval there were 19 510 patients with an overall rate of early definitive treatment at 34·7 (range 9·4-84·7) per cent. In the 1-year follow-up period, 4661 patients (23·9 per cent) had one or more emergency readmissions for complications related to gallstone pancreatitis. Of these, 2692 (57·8 per cent) were readmissions for acute pancreatitis; 911 (33·8 per cent) were within the first 2 weeks of discharge, with the remaining 1781 (66·2 per cent) occurring after the point at which definitive treatment should have been received. Early definitive treatment resulted in a 39 per cent reduction in readmission risk (adjusted risk ratio (RR) 0·61, 95 per cent c.i. 0·58 to 0·65). The risk was further reduced for acute pancreatitis readmissions to 54 per cent in the early definitive treatment group (adjusted RR 0·46, 0·42 to 0·51). In acute gallstone pancreatitis, compliance with recommended early definitive treatment varied considerably, with associated variation in outcomes. Compliance should be used as a quality indicator to improve care. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Treatment and pathogenesis of acute hyperkalemia

PubMed Central

Mushiyakh, Yelena; Dangaria, Harsh; Qavi, Shahbaz; Ali, Noorjahan; Pannone, John; Tompkins, David

2012-01-01

This article focuses on the pathogenesis, clinical manifestations, and various treatment modalities for acute hyperkalemia and presents a systematic approach to selecting a treatment strategy. Hyperkalemia, a life-threatening condition caused by extracellular potassium shift or decreased renal potassium excretion, usually presents with non-specific symptoms. Early recognition of moderate to severe hyperkalemia is vital in preventing fatal cardiac arrhythmias and muscle paralysis. Management of hyperkalemia includes the elimination of reversible causes (diet, medications), rapidly acting therapies that shift potassium into cells and block the cardiac membrane effects of hyperkalemia, and measures to facilitate removal of potassium from the body (saline diuresis, oral binding resins, and hemodialysis). Hyperkalemia with potassium level more than 6.5 mEq/L or EKG changes is a medical emergency and should be treated accordingly. Treatment should be started with calcium gluconate to stabilize cardiomyocyte membranes, followed by insulin injection, and b-agonists administration. Hemodialysis remains the most reliable method to remove potassium from the body and should be used in cases refractory to medical treatment. Prompt detection and proper treatment are crucial in preventing lethal outcomes. PMID:23882341

Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood acute lymphoblastic leukemia (ALL) treatment is usually chemotherapy given in phases and determined by risk group. Radiation therapy, targeted therapy and stem cell transplant are sometimes used. Learn more about newly diagnosed and recurrent ALL in this expert reviewed summary.

Acute appendicitis in children: not only surgical treatment.

PubMed

Caruso, Anna Maria; Pane, Alessandro; Garau, Roberto; Atzori, Pietro; Podda, Marcello; Casuccio, Alessandra; Mascia, Luigi

2017-03-01

An accurate diagnosis of acute appendicitis is important to avoid severe outcome or unnecessary surgery but management is controversial. The aim of study was to evaluate, in younger and older children, the efficacy of conservative management for uncomplicated appendicitis and the outcome of complicated forms underwent early surgery. Children with acute appendicitis were investigated by clinical, laboratory variables and abdominal ultrasound and divided in two groups: complicated and uncomplicated. Complicated appendicitis underwent early surgery; uncomplicated appendicitis started conservative treatment with antibiotic. If in the next 24-48h it was worsening, the conservative approach failed and patients underwent late surgery. A total of 362 pediatric patients were included. One hundred sixty-five underwent early appendectomy; 197 patients were at first treated conservatively: of these, 82 were operated within 24-48h for failure. The total percentage of operated patients was 68.2%. An elevated association was found between surgery and ultrasound. Conservative treatment for uncomplicated appendicitis had high percentage of success (58%). Complications in operated patients were infrequent. Our protocol was effective in order to decide which patients treat early surgically and which conservatively; specific red flags (age and onset) can identified patients at most risk of complications or conservative failure. treatment study. II. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnosis and treatment of acute low back pain.

PubMed

Casazza, Brian A

2012-02-15

Acute low back pain is one of the most common reasons for adults to see a family physician. Although most patients recover quickly with minimal treatment, proper evaluation is imperative to identify rare cases of serious underlying pathology. Certain red flags should prompt aggressive treatment or referral to a spine specialist, whereas others are less concerning. Serious red flags include significant trauma related to age (i.e., injury related to a fall from a height or motor vehicle crash in a young patient, or from a minor fall or heavy lifting in a patient with osteoporosis or possible osteoporosis), major or progressive motor or sensory deficit, new-onset bowel or bladder incontinence or urinary retention, loss of anal sphincter tone, saddle anesthesia, history of cancer metastatic to bone, and suspected spinal infection. Without clinical signs of serious pathology, diagnostic imaging and laboratory testing often are not required. Although there are numerous treatments for nonspecific acute low back pain, most have little evidence of benefit. Patient education and medications such as nonsteroidal anti-inflammatory drugs, acetaminophen, and muscle relaxants are beneficial. Bed rest should be avoided if possible. Exercises directed by a physical therapist, such as the McKenzie method and spine stabilization exercises, may decrease recurrent pain and need for health care services. Spinal manipulation and chiropractic techniques are no more effective than established medical treatments, and adding them to established treatments does not improve outcomes. No substantial benefit has been shown with oral steroids, acupuncture, massage, traction, lumbar supports, or regular exercise programs.

Comparison of various treatment modalities for acute tinnitus.

PubMed

Shim, Hyun Joon; Song, Seong Jun; Choi, A Young; Hyung Lee, Rae; Yoon, Sang Won

2011-12-01

Because in most cases the development of tinnitus is triggered by cochlear damage, there exists the opportunity to eliminate tinnitus while the cochlear lesion is still reversible. Therefore, we evaluated the therapeutic effects of various treatment modalities on acute subjective idiopathic tinnitus (SIT) and investigated prognostic factors affecting the treatment outcome. Prospective, controlled, double-blind trial. A total 107 patients who underwent treatment for unilateral SIT that had developed within the previous 3 months completed the study. The patients were randomly assigned into three groups according to the treatment modality: group I (n = 32), alprazolam orally for 3 months; group II (n = 35), as for group I plus four intratympanic dexamethasone (ITD) injections; and group III (n = 40), as for group II plus four intravenous injections of lipo-prostaglandin E(1) . The improvement rate of group II (75.8%) was significantly higher than that of group I (40.3%; P < .05), and there was no significant difference in the improvement rate of group III (50.0%) compared with groups I and II (P > .05). The cure rates of group II (25.8%) and group III (20.0%) were significantly higher than that of group I (9.8%; P < .05). There was a significant correlation between the cure rate and duration of symptoms. The results of the present study indicate that ITD injection plus alprazolam medication is the best treatment choice for acute SIT within 3 months of development. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial.

PubMed

Holroyd, Kenneth A; Cottrell, Constance K; O'Donnell, Francis J; Cordingley, Gary E; Drew, Jana B; Carlson, Bruce W; Himawan, Lina

2010-09-29

To determine if the addition of preventive drug treatment (β blocker), brief behavioural migraine management, or their combination improves the outcome of optimised acute treatment in the management of frequent migraine. Randomised placebo controlled trial over 16 months from July 2001 to November 2005. Two outpatient sites in Ohio, USA. 232 adults (mean age 38 years; 79% female) with diagnosis of migraine with or without aura according to International Headache Society classification of headache disorders criteria, who recorded at least three migraines with disability per 30 days (mean 5.5 migraines/30 days), during an optimised run-in of acute treatment. Addition of one of four preventive treatments to optimised acute treatment: β blocker (n=53), matched placebo (n=55), behavioural migraine management plus placebo (n=55), or behavioural migraine management plus β blocker (n=69). The primary outcome was change in migraines/30 days; secondary outcomes included change in migraine days/30 days and change in migraine specific quality of life scores. Mixed model analysis showed statistically significant (P≤0.05) differences in outcomes among the four added treatments for both the primary outcome (migraines/30 days) and the two secondary outcomes (change in migraine days/30 days and change in migraine specific quality of life scores). The addition of combined β blocker and behavioural migraine management (-3.3 migraines/30 days, 95% confidence interval -3.2 to -3.5), but not the addition of β blocker alone (-2.1 migraines/30 days, -1.9 to -2.2) or behavioural migraine management alone (-2.2 migraines migraines/30 days, -2.0 to -2.4), improved outcomes compared with optimised acute treatment alone (-2.1 migraines/30 days, -1.9 to -2.2). For a clinically significant (≥50% reduction) in migraines/30 days, the number needed to treat for optimised acute treatment plus combined β blocker and behavioural migraine management was 3.1 compared with optimised acute

The natural history of acute hepatitis C: clinical presentation, laboratory findings and treatment outcomes.

PubMed

Loomba, R; Rivera, M M; McBurney, R; Park, Y; Haynes-Williams, V; Rehermann, B; Alter, H J; Herrine, S K; Liang, T J; Hoofnagle, J H; Heller, T

2011-03-01

Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. To establish natural history and complications of treatment of acute hepatitis C. Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed. Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and hepatitis C virus (HCV) RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4-8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%. Among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Anti-viral treatment with a 24-week course of peginterferon and ribavirin was highly effective, but marked by frequent and severe side effects. Published 2010. This article is a US Government work and is in the public domain in the USA.

The natural history of acute hepatitis C: clinical presentation, laboratory findings, and treatment outcomes

PubMed Central

Loomba, R.; Rivera, M. M.; McBurney, R.; Park, Y.; Haynes-Williams, V.; Rehermann, B.; Alter, H. J.; Herrine, S. K.; Liang, T. J.; Hoofnagle, J. H.; Heller, T.

2017-01-01

Summary Background Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. Aims To establish natural history and complications of treatment of acute hepatitis C. Methods Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed. Results Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and HCV RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4 to 8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%. Conclusion Thus, among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Antiviral treatment with a 24-week course of peginterferon and ribavirin was highly effective but marked by frequent and severe side effects. PMID:21198704

Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study

PubMed Central

Knoops, Sofie; Aldinucci Buzzo, João L.; Boon, Lise; Martens, Erik; Opdenakker, Ghislain; Kolaczkowska, Elzbieta

2017-01-01

Gelatinase B or matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin) and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM), the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2) activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations. PMID:28369077

Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment

PubMed Central

Testoni, Pier Alberto

2014-01-01

Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches. PMID:25493002

Treatment strategies for acute metabolic disorders in neonates

PubMed Central

2011-01-01

Acute metabolic emergencies in neonates represent a challenge to the medical and nursing staff. If not treated optimally, these disorders are associated with poor outcome. Early diagnosis, supportive therapy and specific measures addressing the derranged metabolic process are the gold standards for favorable results. This review highlights treatment strategies for Inborn Errors of Metabolism (IEM) presenting in the neonatal period. PMID:27493313

Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment.

PubMed

Karimi, Karen; Odhav, Ashika; Kollipara, Ramya; Fike, Jesse; Stanford, Carol; Hall, John C

Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician's guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.

[The use of Timalin in the treatment of the acute lung abscess].

PubMed

Tsybikov, M N; Likhanov, I D; Borshchevskiĭ, V S; Kuznik, B I; Tsepelev, V L; Maslo, E Iu; Tsybikov, N N

2012-01-01

The study was aimed to research levels of main acute inflammation phase peptides, coagulative and fibrinolitic plasma activity on the background of traditional treatment and with addition of Timalin in patients with acute lung abscess. The study demonstrated that induction of bioregulative therapy leads to faster normalization of main indicators of SIRS and plasma fibrinolitic activity and eliminates hypercoagulation.

Variability in hyperbaric oxygen treatment for acute carbon monoxide poisoning.

PubMed

Byrne, Brendan T; Lu, Jenny J; Valento, Matthew; Bryant, Sean M

2012-01-01

In patients with acute carbon monoxide (CO) poisoning, we have noted wide clinical variability in both criteria for hyperbaric oxygen (HBO2) treatment as well as HBO2 treatment regimens. Our aim was to survey Midwest hyperbaric centers for insight into specific criteria and protocols for treating acute CO toxicity with HBO2. Hyperbaric centers were identified from the published list of the Undersea and Hyperbaric Medical Society. Ninety-three centers from nine Midwestern states were contacted via telephone. A standard script was used to minimize surveyor bias. Thirty centers that treat CO poisonings were identified. One did not participate in the study. Nineteen reported a specific level of carboxyhemoglobin (COHb) that served as an independent indication for initiation of HBO2 treatment. Four centers used the COHb level as the exclusive indication for HBO2 treatment. Ten centers relied solely on reported symptoms, while the remaining centers used a combination of symptoms plus COHb levels. There were 19 separate treatment protocols. No uniform practice for either the initiation or implementation of HBO2 therapy for CO poisoning exists among U.S. Midwest hyperbaric centers responding to a survey. We see opportunity for specific targeted educational programs as well as further study.

Endovascular Treatment in Emergency Setting of Acute Arterial Injuries After Orthopedic Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carrafiello, Gianpaolo, E-mail: gcarraf@tin.it; Fontana, Federico, E-mail: fede.fontana@libero.it; Mangini, Monica, E-mail: monica.mangini@tin.it

Purpose: To assess the feasibility and effectiveness of emergency endovascular treatment of acute arterial injuries after orthopedic surgery. Materials and Methods: Fifteen patients (mean age 68.3 years) with acute arterial injuries after orthopedic surgery were observed, in particular, 5 patients with pseudoaneurysm, 9 patients with active bleeding, and 1 patient with arterial dissection. Transarterial embolization (TAE) and positioning of covered and noncovered stents were the treatments performed. Follow-up after stent implantation (mean 36 months) was performed with color Doppler US (CDU) at 1, 3, 6, and 12 months and yearly thereafter. Plain X-ray was performed to evidence dislodgment or fracturemore » of the graft. A minimum of 12 months' follow-up is available after TAE. Results: Immediate technical success was obtained in all cases. No major complications occurred. Overall clinical success rate was 100%. During mean follow-up, stent-graft occlusions did not occurred. No recurrence and/or consequence of TAE was registered during a minimum follow-up of 12 months. Conclusions: Percutaneous treatment is a feasible and safe tool for treating arterial injuries because it can provide fast and definitive resolution of the damage. This low-invasiveness approach can be proposed as first-line treatment in patients with acute injuries after orthopedic surgery.« less

Patients' preferences for headache acute and preventive treatment.

PubMed

Mitsikostas, Dimos D; Belesioti, Ioanna; Arvaniti, Chryssa; Mitropoulou, Euthymia; Deligianni, Christina; Kasioti, Elina; Constantinidis, Theodoros; Dermitzakis, Manolis; Vikelis, Michail

2017-10-06

We aimed to explore patients' preferences for headache treatments with a self-administered questionnaire including the Q-No questionnaire for nocebo. Questionnaires from 514 outpatients naïve to neurostimulation and monoclonal antibodies were collected. Patients assessed that the efficacy of a treatment is more important than safety or route of administration. They preferred to use an external neurostimulation device for both acute (67.1%) and preventive treatment (62.8%). Most patients preferred to take a pill (86%) than any other drug given parenterally for symptomatic pharmaceutical treatment. For preventive pharmaceutical treatment, most patients preferred to take a pill once per day (52%) compared to an injection either subcutaneously or intravenously each month (9% and 4%), or three months (15% and 11%). 56.6% of all participants scored more than 15 in Q-No questionnaire indicating potential nocebo behaviors that contributed significantly in their choices. These patient preferences along with efficacy and safety data may help physicians better choose the right treatment for the right person.

Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

PubMed

Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

2010-08-01

Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

Effect of Early Statin Treatment in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

PubMed Central

Sim, Doo Sun; Cho, Kyung Hoon; Ahn, Youngkeun; Kim, Young Jo; Chae, Shung Chull; Hong, Taek Jong; Seong, In Whan; Chae, Jei Keon; Kim, Chong Jin; Cho, Myeong Chan; Rha, Seung-Woon; Bae, Jang Ho; Seung, Ki Bae; Park, Seung Jung

2013-01-01

Background and Objectives The benefit of early statin treatment following acute myocardial infarction (MI) complicated with cardiogenic shock (CS) has not been well studied. We sought to assess the effect of early statin therapy in patients with CS complicating acute MI. Subjects and Methods We studied 553 statin-naive patients with acute MI and CS (Killip class IV) who underwent revascularization therapy between November 2005 and January 2008 at 51 hospitals in the Korea Acute Myocardial Infarction Registry. Patients were divided into 2 groups: those who received statins during hospitalization (n=280) and those who did not (n=273). The influence of statin treatment on a 12-month clinical outcome was examined using a matched-pairs analysis (n=200 in each group) based on the propensity for receiving statin therapy during hospitalization. Results Before adjustment, patients receiving statin, compared to those not receiving statin, had a more favorable clinical profile, were less likely to suffer procedural complications, and more likely to receive adequate medical therapy. Patients receiving statin had lower unadjusted in-hospital mortality and composite rate of mortality, MI, and repeat revascularization at 12 months, which remained significantly lower after adjustment for patient risk, procedural characteristics, and treatment propensity. Conclusion In CS patients with acute MI undergoing revascularization therapy, early statin treatment initiated during hospitalization was associated with lower rates of in-hospital death and 12-month adverse cardiac events. PMID:23508129

Laparoscopic Diagnosis and Treatment of an Acute Epiploic Appendagitis with Torsion and Necrosis Causing an Acute Abdomen

PubMed Central

Castañeda, Pablo; Valencia, Salvador; Cueto, Jorge

2000-01-01

Acute epiploic appendagitis is not as rare as previously thought; but, since the presenting signs and symptoms are not specific, preoperative diagnosis has been rarely made. At the present time, a laparoscopic exploration of the peritoneal cavity will establish the correct diagnosis, and the treatment can be provided during the same procedure. Herein, a case of a 63-year-old female patient with acute abdominal syndrome caused by a necrotic epiploic appendix that was successfully diagnosed and treated laparoscopically is described. A review of the literature is made, as well. PMID:10987404

Antibiotic management of methicillin-resistant Staphylococcus aureus--associated acute pulmonary exacerbations in cystic fibrosis.

PubMed

Fusco, Nicholas M; Toussaint, Kimberly A; Prescott, William Allan

2015-04-01

To review the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated acute pulmonary exacerbations (APEs) in cystic fibrosis (CF). A search of PubMed, MEDLINE, Cochrane Library and Clinicaltrials.gov databases through November 2014 was conducted using the search terms Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, pulmonary exacerbations, and cystic fibrosis. All English-language research articles, case reports, and case series were evaluated. A total of 185 articles were identified related to MRSA and CF; 30 articles that studied treatments of MRSA APE in CF were included. The persistent presence of MRSA in the respiratory tract of patients with CF has been associated with higher morbidity and an increased risk of death. Limited clinical data exist supporting the efficacy of any specific antimicrobial currently available for the treatment of APE secondary to MRSA. Data extrapolated from other populations suggest that vancomycin and linezolid are appropriate first-line treatment options for the treatment of APE secondary to MRSA. Second-line options include doxycycline or minocycline and trimethoprim/sulfamethoxazole, each of which may be useful in patients coinfected with other respiratory pathogens, for which they may provide overlapping coverage. Ceftaroline and ceftobiprole are newer antibiotics that appear to have a potential role in the treatment of APE in CF, but the latter is not currently available to the US market. Although potentially useful, clindamycin is limited by high rates of resistance, telavancin is limited by its toxicity profile, and tigecycline is limited by a lack of demonstrated efficacy for infections that are similar to that seen in the CF population. Studies investigating the clinical utility of the above-cited antibiotics for APE in CF secondary to MRSA are desperately needed to broaden the treatment armamentarium for this medical condition. © The Author(s) 2015.

[Acute inpatient conservative multimodal treatment of complex and multifactorial orthopedic diseases in the ANOA concept].

PubMed

Psczolla, M

2013-10-01

In Germany there is a clear deficit in the non-operative treatment of chronic and complex diseases and pain disorders in acute care hospitals. Only about 20 % of the treatments are carried out in orthopedic hospitals. Hospitals specialized in manual medicine have therefore formed a working group on non-operative orthopedic manual medicine acute care clinics (ANOA). The ANOA has developed a multimodal assessment procedure called the OPS 8-977 which describes the structure and process quality of multimodal and interdisciplinary diagnosis and treatment of the musculoskeletal system. Patients are treated according to clinical pathways oriented on the clinical findings. The increased duration of treatment in the German diagnosis-related groups (DRG) system is compensated for with a supplemental remuneration. Thus, complex and multifactorial orthopedic diseases and pain disorders are conservatively and appropriately treated as inpatient departments of acute care hospitals.

Successful treatment of acute systemic anaphylaxis in a western lowland gorilla (Gorilla gorilla gorilla).

PubMed

Hayman, David T S; King, Tony; Cameron, Kenneth

2010-09-01

This brief communication describes the successful treatment of acute systemic anaphylaxis in a wild-born but captive infant western lowland gorilla (Gorilla gorilla gorilla) in the Republic of Congo. The infant demonstrated signs of acute respiratory distress, lingual swelling, and reaction to intradermal tuberculin, given 55 hr earlier. Details of the treatment with steroids, anesthetic induction, and i.v. epinephrine are all reported, and potential antigens that may have initiated the anaphylactic shock are discussed.

Differential effects of acute amphetamine and phencyclidine treatment and withdrawal from repeated amphetamine or phencyclidine treatment on social interaction and social memory in rats.

PubMed

Li, Ming; He, Wei; Munro, Rebecca

2012-06-01

Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals with the same partner rat (termed "AAAA" day). One day later, the rats were tested with the previous partner in the first three sessions and with a new partner rat in the final session (termed "AAAB" day). The results show that acute AMPH treatment (1.5 mg/kg, sc) significantly reduced the time spent on social interaction, but did not affect social recognition on the first day. Acute AMPH only disrupted social recognition on the second day of drug testing. In contrast, acute PCP treatment (2.0 mg/kg, sc) had no effect on time spent on social interaction, but did significantly disrupt social recognition on both days. Withdrawal from repeated AMPH (3.0 mg/kg/day for 7 days, ip) or PCP (5.0 mg/kg/twice daily for 7 days, ip) treatment did not affect social interaction or social recognition, indicating a lack of long-term detrimental effect of repeated AMPH or PCP treatment. These results suggest that acute AMPH treatment at a low dose (1.5 mg/kg) may be useful in modeling social withdrawal symptoms of schizophrenia, whereas acute PCP treatment at a similar dose range (2.0 mg/kg) may be useful in modeling the social cognitive deficit of schizophrenia. © 2012 The Institute of Psychology, Chinese Academy of Sciences and Blackwell Publishing Asia Pty Ltd.

Treatments for Reversing Warfarin Anticoagulation in Patients with Acute Intracranial Hemorrhage: A Structured Literature Review

DTIC Science & Technology

2011-07-08

available soon. Treatments for reversing warfarin anticoagulation in patients with acute intracranial hemorrhage: a structured literature review...DATE 08 JUL 2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE Treatments For Reversing Warfarin ...distribution unlimited 13. SUPPLEMENTARY NOTES International Journal of Emergency Medicine 2011 14. ABSTRACT The acute management of patients on warfarin

Compatibility of cholecalciferol, haloperidol, imipramine hydrochloride, levodopa/carbidopa, lorazepam, minocycline hydrochloride, tacrolimus monohydrate, terbinafine, tramadol hydrochloride and valsartan in SyrSpend SF PH4 oral suspensions.

PubMed

Polonini, H C; Silva, S L; Cunha, C N; Brandão, M A F; Ferreira, A O

2016-04-01

A challenge with compounding oral liquid formulations is the limited availability of data to support the physical, chemical and microbiological stability of the formulation. This poses a patient safety concern and a risk for medication errors. The objective of this study was to evaluate the compatibility of the following active pharmaceutical ingredients (APIs) in 10 oral suspensions, using SyrSpend SF PH4 (liquid) as the suspending vehicle: cholecalciferol 50,000 IU/mL, haloperidol 0.5 mg/mL, imipramine hydrochloride 5.0 mg/mL, levodopa/carbidopa 5.0/1.25 mg/mL, lorazepam 1.0 mg/mL, minocycline hydrochloride 10.0 mg/mL, tacrolimus monohydrate 1.0 mg/mL, terbinafine 25.0 mg/mL, tramadol hydrochloride 10.0 mg/mL and valsartan 4.0 mg/mL. The suspensions were stored both refrigerated (2 - 8 degrees C) and at controlled room temperature (20 - 25 degrees C). This is the first stability study for these APIs in SyrSpend SF PH4 (liquid). Further, the stability of haloperidol,ilmipramine hydrochloride, minocycline, and valsartan in oral suspension has not been previously reported in the literature. Compatibility was assessed by measuring percent recovery at varying time points throughout a 90 days period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV). Given the percentage of recovery of the APIs within the suspensions, the beyond-use date of the final preparations was found to be at least 90 days for most suspensions both refrigerated and at room temperature. Exceptions were: Minocycline hydrochloride at both storage temperatures (60 days), levodopa/carbidopa at room temperature (30 days), and lorazepam at room temperature (60 days). This suggests that compounded suspensions of APIs from different pharmacological classes in SyrSpend SF PH4 (liquid) are stable.

Differentiating Acute Otitis Media and Acute Mastoiditis in Hospitalized Children.

PubMed

Laulajainen-Hongisto, Anu; Aarnisalo, Antti A; Jero, Jussi

2016-10-01

Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children.

A strategic plan to accelerate development of acute stroke treatments.

PubMed

Marler, John R

2012-09-01

In order to reenergize acute stroke research and accelerate the development of new treatments, we need to transform the usual design and conduct of clinical trials to test for small but significant improvements in effectiveness, and treat patients as soon as possible after stroke onset when treatment effects are most detectable. This requires trials that include thousands of acute stroke patients. A plan to make these trials possible is proposed. There are four components: (1) free access to the electronic medical record; (2) a large stroke emergency network and clinical trial coordinating center connected in real time to hundreds of emergency departments; (3) a clinical trial technology development center; and (4) strategic leadership to raise funds, motivate clinicians to participate, and interact with politicians, insurers, legislators, and other national and international organizations working to advance the quality of stroke care. © 2012 New York Academy of Sciences.

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

PubMed

Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

2016-06-01

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

PubMed

Milone, Jorge H; Enrico, Alicia

2009-12-01

The presence of the Philadelphia chromosome is a poor prognosis factor in acute lymphoblastic leukemia (ALL), in both children and adults. Using molecular techniques of the gen bcr/abl, it is possible to detect the abnormality, in up to the 40% of adult patients. The unsatisfactory results with conventional chemotherapy schemes have determined the intensification of the treatments and the consideration of allogenic bone marrow transplants as the best therapeutic instance. The development of tyrosine kinase inhibitors have become a therapeutic improvement in the treatment of Philadelphia chromosome-positive ALL, being combined with chemotherapy schemes, only in a selected group of patients, even in therapeutic programs that include transplant.

A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression.

PubMed

Reinares, María; Rosa, Adriane R; Franco, Carolina; Goikolea, José Manuel; Fountoulakis, Kostas; Siamouli, Melina; Gonda, Xenia; Frangou, Sophia; Vieta, Eduard

2013-03-01

Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database. Eligibility criteria included active comparator-controlled or placebo-controlled randomized studies involving monotherapy or combination therapy. A total of 18 RCTs fulfilled the inclusion criteria. Studies supported the efficacy of divalproex as monotherapy in acute bipolar depression but small sample size was a common methodological limitation. Findings were inconclusive for lamotrigine and carbamazepine although overall lamotrigine may have a beneficial but modest effect. Negative results were found for levetiracetam and gabapentin but the evidence base on these agents is scant. All anticonvulsants were generally well tolerated. No double-blind RCTs were found for the use of other anticonvulsants such as oxcarbazepine, licarbazepine, zonisamide, retigabine, pregabalin, tiagabine, felbamate and vigabatrine in the acute treatment of bipolar depression. To sum up, taking into consideration the efficacy and tolerability profiles of anticonvulsants, current evidence supports the use of divalproex and lamotrigine in the treatment of acute bipolar depression. However, available data for most other anticonvulsants are inconclusive and further RCTs with larger sample sizes are needed before drawing firm conclusions.

Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

For acute lymphoblastic leukemia (ALL), the 5-year survival rate has improved significantly since 1975. Get information about risk factors, signs, diagnosis, molecular features, survival, risk-based treatment assignment, and induction and postinduction therapy for children and adolescents with newly diagnosed and recurrent ALL.

[Comparative study of two treatment methods for acute periodontal abscess].

PubMed

Jin, Dong-mei; Wang, Wei-qian

2012-10-01

The aim of this short-term study was to compare the clinical efficacy of 2 different methods to treat acute periodontal abscesses. After patient selection, 100 cases of acute periodontal abscess were randomly divided into two groups. The experimental group was treated by supra- and subgingival scaling, while the control group was treated by incision and drainage. A clinical examination was carried out to record the following variables: subjective clinical variables including pain, edema, redness and swelling; objective clinical variables including gingival index(GI), bleeding index(BI), probing depth(PD),suppuration, lymphadenopathy and tooth mobility. The data was analyzed with SPSS 19.0 software package. RESULES: Subjective clinical variables demonstrated statistically significant improvements with both methods from the first day after treatment and lasted for at least 30 days(P<0.05), but the results of experimental group showed much better than the control group 1 day and 7 days after treatment. 30 days after treatment, there was no significant difference between the two groups in pain and swelling improvement(P>0.05), but the experimental group showed more improvement in edema and redness than the control group(P<0.05).On improving objective variables, the experimental group showed significant improvement in GI,BI,PD and suppuration 1 day after treatment(P<0.05).After 7 days, all objective clinical variables in the experimental group improved significantly(P<0.05) in the control group, there were significant improvements in GI,suppuration,lymphadenopathy and tooth mobility(P<0.05) but the four variables of the experimental group showed more improvement than the control group(P<0.05).After 30 days, all objective clinical variables improved significantly in both groups as compared to baseline, but in the experimental group, improvements were more significant regarding to GI,BI,PD,suppuration and tooth mobility(P<0.05). The method of supra- and subgingival

Treatment of acute vivax malaria with tafenoquine.

PubMed

Nasveld, Peter; Kitchener, Scott

2005-01-01

Tafenoquine is an 8-aminoquiniline related to primaquine with pre-clinical activity against a range of malaria species. We treated two acute cases of vivax malaria with tafenoquine (800 mg over three days) alone, instead of conventional chloroquine (1500 mg over three days) and primaquine (420 mg over 14 days). In addition to the convenience of this regimen, the rapid parasite clearances observed, coupled with a good clinical response and lack of recrudescence or relapse, indicate that further investigation of tafenoquine in the treatment of vivax malaria is warranted.

Efficacy of parecoxib, sumatriptan, and rizatriptan in the treatment of acute migraine attacks.

PubMed

Müller, Thomas; Lohse, Lutz

2011-01-01

Triptans and analgetic nonsteroidal inflammatory drugs reduce acute pain syndromes in migraine. A further treatment option for an acute headache attack in patients with migraine may be the application of cyclooxygenase-2-specific inhibitors, as they have anti-inflammatory and analgesic properties. The objective of this pilot study was to investigate the effects of an oral fast-dissolving tablet of 10 mg of rizatriptan, an intravenous infusion of 40 mg of parecoxib, and a subcutaneous pen injection of sumatriptan (6 mg/0.5 mL) on pain relief in 3 cohorts of patients with episodic migraine. They were treated owing to the acute onset of a pain attack as a case of emergency. They were randomized to treatment with sumatriptan, rizatriptan, or parecoxib. The participants completed a visual analog scale for pain intensity at baseline before the drug administration and then after intervals of 20, 30, 60, and 120 minutes. Rizatriptan, parecoxib, and sumatriptan reduced pain symptoms. Twenty and 30 minutes after drug intake, rizatriptan was more efficacious than parecoxib and sumatriptan, and parecoxib was more effective than sumatriptan. Only a significant difference between rizatriptan and sumatriptan was found after 60 and 120 minutes. This trial demonstrates the effectiveness of a parecoxib infusion in the treatment of acute migraine and that the circumvention of the first pass effect of the liver by rizatriptan may be beneficial for fast pain relief.

Neuropsychological late effects of treatment for acute leukemia in children with Down syndrome.

PubMed

Roncadin, Caroline; Hitzler, Johann; Downie, Andrea; Montour-Proulx, Isabelle; Alyman, Cheryl; Cairney, Elizabeth; Spiegler, Brenda J

2015-05-01

Children with Down syndrome (DS) have an elevated risk of developing acute leukemia, but little is known about treatment-related neuropsychological morbidity because they are systematically excluded from research in this area. The current study investigated neuropsychological outcomes in children with DS treated for acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) compared to children with DS with no history of cancer. Participants were 4 to 17 years of age at testing and were administered measures of intelligence, academic achievement, language, visual-motor and fine-motor skills, and adaptive function. Patients had been off treatment for at least 2 years. The AML group (N = 12) had significantly lower verbal intelligence and receptive vocabulary compared to controls (N = 21). By contrast, the ALL group (N = 14) performed significantly worse than controls on measures of verbal intelligence, spelling, receptive and expressive vocabulary, visual-motor skills, and adaptive function. Patients with DS treated for AML may have specific post-treatment morbidity in verbal function, whereas those treated for ALL have broader morbidity affecting multiple neuropsychological domains and overall adaptive function. We hypothesize that the broader impairment profile of ALL survivors may be related to a combination of the longer duration of central nervous system-directed treatment for ALL compared to AML and the concomitant limited access to intervention opportunities during active treatment. © 2014 Wiley Periodicals, Inc.

[Advantages and problems of traditional Chinese medicine in treatment of acute pharyngitis].

PubMed

Zhang, Xia; Xie, Yan-Ming; Li, Guang-Xi; Gao, Yang; Zhao, Yuan-Chen; Tang, Jing-Jing; Yao, Xiao-Yan; Li, Meng

2017-10-01

This paper systematically studies relevant literatures at home and abroad in recent years. China National Knowledge Internet (CNKI) was used to collect the literatures for acute pharyngitis treated with traditional Chinese medicine from January 1, 2006, to December 31, 2016, and the bibliometric method was employed for statistical analysis. A total of 493 papers were preliminarily selected. According to the inclusion criteria and exclusion criteria, 182 eligible articles were selected. According to the evaluation and analysis of the literatures, the Guidelines for Clinical Research of New Drugs is currently used as the common standards for the diagnosis and treatment of acute pharyngitis; Chinese patent medicines are the main traditional Chinese medicine for treating this disease; Decoctions for treatment of this disease include Lonicerae Japonicae Flos, Scutellariae Radix, Platycodonis Radix, Forsythiae Fructus, Glycyrrhizae Radix et Rhizoma, Scrophdlariae Radix, Isatidis Radix, and Ophiopogonis Radix; The bloodletting puncture is the common external therapy. Traditional Chinese medicine and Western medicine have their own characteristics in the treatment of this disease. Western medicine for the treatment of acute pharyngitis are mainly antiviral, antibiotic and glucocorticoid drugs, whose disadvantages are toxicity, side effects, drug resistance and double infections. Traditional Chinese medicine doctors have rich experiences in the treatment of the disease, which is characterized by treatment determination based on syndrome differentiation, safe and reliable medication, significant curative effect, low drug resistance, and wide varieties of traditional Chinese medicine forms, convenient portability and taking, low price, and low toxic and side effects. It is an arduous and significant task to explore traditional Chinese medicine, and study and develop new-type effective drugs. Copyright© by the Chinese Pharmaceutical Association.

Antibiotic treatment of acute respiratory infections in acute care settings.

PubMed

Gonzales, Ralph; Camargo, Carlos A; MacKenzie, Thomas; Kersey, Ayanna S; Maselli, Judith; Levin, Sara K; McCulloch, Charles E; Metlay, Joshua P

2006-03-01

To examine the patterns of antibiotic use for acute respiratory tract infections (ARIs) in acute care settings. Chart reviews were performed retrospectively on a random sample of adult ARI visits to seven Veterans Affairs (VA) and seven non-VA emergency departments (EDs) for the period of November 2003 to February 2004. Visits were limited to those discharged to home and those with primary diagnoses of antibiotic-responsive (pneumonia, acute exacerbation of chronic bronchitis, pharyngitis, sinusitis) and antibiotic-nonresponsive conditions (acute bronchitis, nonspecific upper respiratory tract infection [URI]). Results are expressed as adjusted odds ratios with 95% confidence intervals. Of 2,270 ARI visits, 62% were for antibiotic-nonresponsive diagnoses. Seventy-two percent of acute bronchitis and 38% of URI visits were treated with antibiotics (p < 0.001). Stratified analyses show that antibiotic prescription rates were similar among attending-only and housestaff-associated visits for antibiotic-responsive diagnoses (p = 0.11), and acute bronchitis (76% vs. 59%; p = 0.31). However, the antibiotic prescription rate for URIs was greater for attending-only visits compared with housestaff-associated visits (48% vs. 15%; p = 0.01). Antibiotic prescription rates for total ARIs varied between sites, ranging from 42% to 89%. Patient age, gender, race and ethnicity, smoking status, comorbidities, and clinical setting (VA vs. non-VA) were not independently associated with antibiotic prescribing. Acute care settings are important targets for reducing inappropriate antibiotic prescribing. The mechanisms accounting for lower antibiotic prescription rates observed with housestaff-associated visits merit further study.

Recent advances in the treatment of colonic diverticular disease and prevention of acute diverticulitis

PubMed Central

Elisei, Walter; Tursi, Antonio

2016-01-01

The incidence of diverticulosis and diverticular disease of the colon is increasing worldwide. Although the majority of patients remains asymptomatic long-life, the prevalence of diverticular disease of the colon, including acute diverticulitis, is substantial and is becoming a significant burden on National Health Systems in terms of direct and indirect costs. Focus is now being drawn on identifying the correct therapeutic approach by testing various treatments. Fiber, non-absorbable antibiotics and probiotics seem to be effective in treating symptomatic and uncomplicated patients, and 5-aminosalicylic acid might help prevent acute diverticulitis. Unfortunately, robust evidence on the effectiveness of a medical strategy to prevent acute diverticulitis recurrence is still lacking. We herein provide a concise review on the effectiveness and future perspectives of these treatments. PMID:26752946

[Peppermint oil in the acute treatment of tension-type headache].

PubMed

Göbel, H; Heinze, A; Heinze-Kuhn, K; Göbel, A; Göbel, C

2016-06-01

Tension-type headache is the most frequent form of headache. The local topical treatment with peppermint oil (oleum menthae piperitae) has proven to be significantly more effective than placebo in controlled studies. Peppermint oil targets headache pathophysiology in multiple ways. The efficacy is comparable to that of acetylsalicylic acid or paracetamol. Solutions of 10 % peppermint oil in ethanol are licensed for the treatment of tension-type headache in adults and children above 6 years. It is included in treatment recommendations and guidelines by the respective professional societies and is regarded as a standard treatment for the acute therapy of tension-type headaches.

Successful Treatment of Disseminated Cryptococcal Infection in a Pediatric Acute Lymphoblastic Leukemia Patient During Induction

PubMed Central

Heath, Jessica L.; Yin, Dwight E.; Wechsler, Daniel S.; Turner, David A.

2015-01-01

Disseminated cryptococcal infection is rarely reported in the setting of pediatric acute leukemia, despite the immunocompromised state of these patients. However, when present, disseminated cryptococcal infection poses treatment challenges and is associated with significant morbidity and mortality. Treatment of invasive fungal disease in a child with acute leukemia requires a delicate balance between anti-fungal and anti-neoplastic therapy. This balance is particularly important early in the course of leukemia, since both the underlying disease and overwhelming infection can be life threatening. We describe the successful management of life-threatening disseminated cryptococcosis in a child with acute lymphoblastic leukemia during induction therapy. PMID:22258349

Acute mesenteric ischemia and hepatic infarction after treatment of ectopic Cushing's syndrome.

PubMed

Takayasu, Shinobu; Murasawa, Shingo; Yamagata, Satoshi; Kageyama, Kazunori; Nigawara, Takeshi; Watanuki, Yutaka; Kimura, Daisuke; Tsushima, Takao; Sakamoto, Yoshiyuki; Hakamada, Kenichi; Terui, Ken; Daimon, Makoto

2017-01-01

Patients with Cushing's syndrome and excess exogenous glucocorticoids have an increased risk for venous thromboembolism, as well as arterial thrombi. The patients are at high risk of thromboembolic events, especially during active disease and even in cases of remission and after surgery in Cushing's syndrome and withdrawal state in glucocorticoid users. We present a case of Cushing's syndrome caused by adrenocorticotropic hormone-secreting lung carcinoid tumor. Our patient developed acute mesenteric ischemia after video-assisted thoracoscopic surgery despite administration of sufficient glucocorticoid and thromboprophylaxis in the perioperative period. In addition, our patient developed hepatic infarction after surgical resection of the intestine. Then, the patient was supported by total parenteral nutrition. Our case report highlights the risk of microthrombi, which occurred in our patient after treatment of ectopic Cushing's syndrome. Guidelines on thromboprophylaxis and/or antiplatelet therapy for Cushing's syndrome are acutely needed. The present case showed acute mesenteric thromboembolism and hepatic infarction after treatment of ectopic Cushing's syndrome.Patients with Cushing's syndrome are at increased risk for thromboembolic events and increased morbidity and mortality.An increase in thromboembolic risk has been observed during active disease, even in cases of remission and postoperatively in Cushing's syndrome.Thromboprophylaxis and antiplatelet therapy should be considered in treatment of glucocorticoid excess or glucocorticoid withdrawal.

Remission and Recovery in the Treatment for Adolescents with Depression Study (TADS): Acute and Long-term Outcomes

PubMed Central

Kennard, Betsy D.; Silva, Susan G.; Tonev, Simon; Rohde, Paul; Hughes, Jennifer L.; Vitiello, Benedetto; Kratochvil, Christopher J.; Curry, John F.; Emslie, Graham J.; Reinecke, Mark; March, John

2010-01-01

Objective We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS). Method TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder (MDD) to 12 weeks of treatment to fluoxetine (FLX), cognitive behavioral therapy (CBT), their combination (COMB), or pill placebo (PBO). The PBO group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at week 12 (acute phase remitters) and week 18 (continuation phase remitters) are summarized. We also examined whether residual symptoms at the end of 12 weeks of acute treatment predicted later remission. Results At Week 36, the estimated remission rates for intention-to-treat cases were: COMB: 60%, FLX: 55%; CBT: 64%; overall: 60%. Paired comparisons reveal that at week 24 all active treatments converge on remission outcomes. The recovery rate at Week 36 was 65% for acute phase remitters and 71% for continuation phase remitters, with no significant between-treatment differences in recovery rates. Residual symptoms at the end of acute treatment predicted failure to achieve remission at weeks 18 and 36. Conclusions The majority of depressed adolescents in all three treatment modalities achieved remission at the end of nine months of treatment. PMID:19127172

OKT3 treatment for steroid-resistant acute rejection in kidney transplantation.

PubMed

Sevmis, S; Emiroglu, R; Karakayali, F; Yagmurdur, M C; Dalgic, A; Moray, G; Haberal, M

2005-09-01

Orthoclone (OKT3, Ortho Biotech Inc, USA) monoclonal antilymphocyte antibody is a powerful T-cell-specific immunosuppressive agent. OKT3 has been used for induction therapy in kidney and liver transplantation, as well as to treat acute or steroid-resistant acute rejection episodes (ARE). This study was a retrospective analysis of 43 renal transplant recipients who developed steroid-resistant ARE and were treated with OKT3 between September 1994 and June 2004. The recipients were 36 men and 7 women of mean age 32.7 +/- 11.6 years (range, 19 to 48 years). The mean time from transplantation to OKT3 treatment was 7.2 +/- 6.7 months. Thirty-four episodes (79.1%) responded to OKT3 therapy with improved graft function, but the remaining 9 (20.9%) grafts did not respond. Among the 34 OKT3 responders, the mean serum creatinine decreased from 3.96 +/- 2.5 mg/dL to 2.45 +/- 1.77 mg/dL after treatment. Eleven (25.6%) of the 43 patients experienced minor side effects: fever, dyspnea, tachycardia, bradycardia. One patient (2.3%) developed acute pulmonary edema; one (2.3%), cytomegalovirus infection; and eight (18.6%), bacterial infections. The 1-, 3-, and 5-year graft survival rates for the 34 patients who responded to OKT3 therapy were 96%, 93%, and 85%, respectively. All patients are currently alive. The results indicate that OKT3 is a safe, effective treatment choice for steroid-resistant ARE in kidney transplantation.

The effect of root surface conditioning on smear layer removal in periodontal regeneration (a scanning electron microscopic study)

NASA Astrophysics Data System (ADS)

Fidyawati, D.; Soeroso, Y.; Masulili, S. L. C.

2017-08-01

The role of root surface conditioning treatment on smear layer removal of human teeth is affected by periodontitis in periodontal regeneration. The objective of this study is to analyze the smear layer on root surface conditioned with 2.1% minocycline HCl ointment (Periocline), and 24% EDTA gel (Prefgel). A total of 10 human teeth indicated for extraction due to chronic periodontitis were collected and root planed. The teeth were sectioned in thirds of the cervical area, providing 30 samples that were divided into three groups - minocycline ointment treatment, 24% EDTA gel treatment, and saline as a control. The samples were examined by scanning electron microscope. No significant differences in levels of smear layer were observed between the minocycline group and the EDTA group (p=0.759). However, there were significant differences in the level of smear layer after root surface treatment in the minocycline and EDTA groups, compared with the control group (p=0.00). There was a relationship between root surface conditioning treatment and smear layer levels following root planing.

Chemical pleurodesis for prolonged postoperative air leak in primary spontaneous pneumothorax.

PubMed

How, Cheng-Hung; Tsai, Tung-Ming; Kuo, Shuenn-Wen; Huang, Pei-Ming; Hsu, Hsao-Hsun; Lee, Jang-Ming; Chen, Jin-Shing; Lai, Hong-Shiee

2014-05-01

Prolonged air leak is the most common complication after thoracoscopic operation for primary spontaneous pneumothorax (PSP), and the role of chemical pleurodesis in treating air leaks remains unclear. This study evaluated the safety and efficacy of chemical pleurodesis with a comparison between minocycline and OK-432. Between 1994 and 2011, 1083 PSP patients were treated by thoracoscopic operation. After the operation, patients with persistent air leak for 3 days or more were managed by minocycline or OK-432 pleurodesis. The demographic and outcome data for these patients were collected by retrospective chart review. Seventy-nine patients (7.3%) with prolonged air leak after thoracoscopy underwent minocycline pleurodesis (60 patients) or OK-432 pleurodesis (19 patients) as the primary treatment. The primary success rate was 63% (38/60) for minocycline pleurodesis and 95% (18/19) for OK-432 pleurodesis (p = 0.009). Postpleurodesis pain was common and comparable between the two groups. No major complications were noted after a total of 121 treatments. Patients undergoing primary OK-432 pleurodesis had shorter durations of postpleurodesis chest drainage (mean 8.5 vs. 2.3 days; p < 0.001) and postoperative hospital stay (mean 11.9 vs. 6.8 days; p < 0.001) than those undergoing primary minocycline pleurodesis. After a median follow-up of 16 months, recurrence was noted in one patient in the OK-432 group and none in the minocycline group. Long-term pulmonary function in the two groups was comparable. Chemical pleurodesis using OK-432 or minocycline is safe and convenient for prolonged air leak after thoracoscopic treatment for PSP. Our experience suggested that OK-432 may be more effective than minocycline in reducing air leak. Copyright © 2013. Published by Elsevier B.V.

Biologically based treatment of immature permanent teeth with pulpal necrosis: a case series.

PubMed

Jung, Il-Young; Lee, Seung-Jong; Hargreaves, Kenneth M

2012-06-01

This case series reports the outcomes of 8 patients (ages 9-4 years) who presented with 9 immature permanent teeth with pulpal necrosis and apical periodontitis. During treatment, 5 of the teeth were found to have at least some residual vital tissue remaining in the root canal systems. After NaOCI irrigation and medication with ciprofloxacin, metronidazole, and minocycline, these teeth were sealed with mineral trioxide aggregate and restored. The other group of 4 teeth had no evidence of any residual vital pulp tissue. This second group of teeth was treated with NaOCl irrigation and medicated with ciprofloxacin, metronidazole, and minocycline followed by a revascularization procedure adopted from the trauma literature (bleeding evoked to form an intracanal blood clot). In both groups of patients, there was evidence of satisfactory postoperative clinical outcomes (1-5 years); the patients were asymptomatic, no sinus tracts were evident, apical periodontitis was resolved, and there was radiographic evidence of continuing thickness of dentinal walls, apical closure, or increased root length.

Lactobacillus acidophilus Mixture in Treatment of Children Hospitalized With Acute Diarrhea.

PubMed

Pinto, Jamie M; Petrova, Anna

2016-11-01

Despite unproven effectiveness, Lactobacillus acidophilus is a widely used probiotic in the treatment of pediatric diarrhea. In this report, we evaluated the association between length of stay (LOS) for 290 young children hospitalized with acute diarrhea and adjuvant therapy with a probiotic mixture containing 80% L acidophilus that was included in treatment for 22.4% of them. Overall, no association between LOS and use of L acidophilus was recorded after controlling for age, length of diarrhea symptoms, duration of intravenous fluids, and prior exposure to antibiotic. However, LOS was directly associated with use of L acidophilus in children with negative stool studies, and no such association was recorded in children with positive stool for rotavirus or other infections. We concluded that adjuvant therapy with L acidophilus mixture is not beneficial for young children hospitalized with acute diarrhea. © The Author(s) 2015.

Clinical and cognitive insight in patients with acute-phase psychosis: Association with treatment and neuropsychological functioning.

PubMed

Poyraz, Burç Çağri; Arikan, Mehmet Kemal; Poyraz, Cana Aksoy; Turan, Şenol; Kani, Ayşe Sakalli; Aydin, Eser; İnce, Ezgi

2016-10-01

The severity of psychopathology cannot fully explain deficits in the multi-dimensional construct of insight. The aim of this study was to evaluate the correlates and associations of clinical and cognitive insight in patients in an acute phase of psychosis and to analyse the impact of acute treatment on these variables. This study examined 47 inpatients who were recently hospitalized with acute exacerbation of schizophrenia. All subjects were assessed at both admission and discharge with the Positive and Negative Syndrome Scale (PANSS), Schedule for the Assessment of Insight-Expanded Version (SAI-E), Beck Cognitive Insight Scale (BCIS), and a neurocognition battery. Patients with schizophrenia gained clinical insight after treatment. Cognitive insight did not change significantly after treatment. Insight showed significant negative correlations with positive symptoms and general psychopathology, but not with negative symptoms. Clinical insight was not associated with neuropsychological functioning in this cohort. Gaining clinical insight in the acute phase of illness was associated with the remission of positive symptoms, but not with neuropsychological functioning. Some significant correlations between clinical and cognitive insights were detected, which suggests that cognitive insight contributes to clinical insight but is not treatment-dependent. Long-term treatment may be required to understand the contribution of insight to the outcome of patients with schizophrenia.

The pharmacokinetics and clinical efficacy of AVP-825: a potential advancement for acute treatment of migraine.

PubMed

Cady, Roger

2015-01-01

Oral triptans have dominated the prescription market for acute treatment of migraine for nearly 25 years. Today, patients often express dissatisfaction with prescribed acute treatment in part because they do not have confidence that the therapy will provide consistent efficacy over time. Major limitations to sustained successful use of oral triptans are their relatively slow onset of meaningful clinical benefit and variable absorption/efficacy due to impaired gastrointestinal function during migraine. AVP-825, a new intranasal delivery system for sumatriptan , may be an effective alternative to oral triptans. This article reviews AVP-825, which deposits low-dose sumatriptan powder deep into the vascular mucosa of the posterior nose, allowing rapid absorption of drug into the systemic circulation. Studies suggest that AVP-825 is a highly effective, well-tolerated acute treatment for episodic migraine. Oral triptans are limited in providing effective patient-centered outcomes to migraine patients. Failed or suboptimal abortive treatment of migraine is a major driver of migraine chronification and increases in healthcare costs. AVP-825 is an easy to use, novel, breath-powered intranasal delivery system that provides early onset of efficacy with low systemic drug exposure and few triptan-associated adverse events. AVP-825 will be a welcomed therapeutic tool for the acute treatment of migraine.

Neonatal capsaicin treatment impairs vasopressin-mediated blood pressure recovery following acute hypotension.

PubMed Central

Bennett, T.; Gardiner, S. M.

1984-01-01

Rats were treated with a single injection of either capsaicin (50 mg kg-1 s.c.) or vehicle on day 2 after birth. When the animals were adult, they were challenged with osmotic (water deprivation) and haemodynamic (acute hypotension) stimuli that normally evoke vasopressin release. Capsaicin-treated and vehicle-injected rats showed similar body weight losses and plasma osmolalities following 48 h of water deprivation. Thus it appears that neonatal treatment with capsaicin does not impair the antidiuretic response to plasma hyperosmolality. Following acute ganglion blockade in the presence of angiotensin converting enzyme inhibition, there was some recovery of blood pressure in the vehicle-injected rats, but recovery was significantly (P less than 0.001) less in the capsaicin-treated animals. The recovery may be attributed to vasopressin since it was abolished by an antagonist selective for the pressor action of the peptide (d(CH2)5DAVP). These results suggest that neonatal treatment with capsaicin impairs vasopressin-mediated recovery of blood pressure following acute hypotension. The possible involvement of baro- or chemoreceptor afferents is discussed. PMID:6704593

Causes and Treatment of Acute Ischemic Stroke During Pregnancy.

PubMed

Terón, Ina; Eng, Melissa S; Katz, Jeffrey M

2018-05-21

Treatment recommendations for pregnancy associated ischemic stroke are scarce. This may be due to the fact that, in general, obstetricians tend not to make recommendations for stroke patients and neurologists are not commonly involved in the care of pregnant women. Herein, we review the multiple etiologies of ischemic stroke during pregnancy, considerations for diagnostic testing, and acute treatment and prevention options, including associated risks specific to the pregnant and puerperal state. Intravenous tissue plasminogen activator (tPA) and endovascular thrombectomy have been used successfully to treat pregnant women with acute ischemic stroke. Recent national guidelines recommend considering tPA use during pregnancy for moderate and severe strokes if the potential benefits offset the risks of uterine hemorrhage. Pregnancy-associated ischemic stroke is rare, but can be devastating, and recanalization therapy should not be systematically withheld. Women who are at risk for stroke should be followed carefully, and providers caring for pregnant women should be educated regarding stroke signs and symptoms. Many of the standard post stroke diagnostic modalities may be used safely in pregnancy, and primary and secondary stroke prevention therapy must be tailored to avoid fetal toxicity.

Treatment of diverticular disease of the colon and prevention of acute diverticulitis: a systematic review.

PubMed

Maconi, Giovanni; Barbara, Giovanni; Bosetti, Cristina; Cuomo, Rosario; Annibale, Bruno

2011-10-01

Diverticular disease of the colon is a common disorder, characterized by recurrent symptoms and complications such as diverticulitis, requiring hospital admissions and surgery. This study aimed to systematically review the evidence for medical therapy of diverticular disease in reducing symptoms and preventing acute diverticulitis. MEDLINE and Embase databases (1966 to February 2010). The studies selected were prospective clinical trials on uncomplicated diverticular disease of the colon. Four investigators independently reviewed articles, extracted data, and assessed study quality according to standardized criteria. The main outcomes measured were improvement in symptoms, complete remission of symptoms, and prevention of acute diverticulitis. We identified 31 studies, including 6 placebo-controlled trials. The methodological quality of these studies was suboptimal. Only 10 trials provided a detailed description of the patient history, 8 assessed symptoms by the use of a validated questionnaire, and 14 appropriately defined inclusion and exclusion criteria. Only one long-term double-blind placebo-controlled study was identified. This reported a significant improvement in symptoms and greater prevalence of symptom-free patients at 1 year with fiber plus rifaximin in comparison with fiber alone. The efficacy of treatment in preventing acute diverticulitis was evaluated in 11 randomized trials. Four trials compared rifaximin plus fiber vs fiber alone and failed to show a significant difference between treatments. However, cumulative data from these trials revealed a significant benefit following rifaximin and fiber (1-year rate of acute diverticulitis: 11/970 (1.1%) vs 20/690 (2.9%); P = .012), but with a number needed to treat of 57, to prevent an attack of acute diverticulitis. : Heterogeneity of the study design, patients' characteristics, regimens and combination of studied treatment, and outcome reporting precluded the pooling of results and limited

Effect of switching to risperidone after unsuccessful treatment with aripiprazole on plasma monoamine metabolites level in the treatment of acute schizophrenia.

PubMed

Miura, Itaru; Takeuchi, Satoshi; Katsumi, Akihiko; Kanno, Keiko; Watanabe, Kenya; Mashiko, Hirobumi; Niwa, Shin-Ichi

2012-09-01

In the treatment of acute schizophrenia, risperidone and aripiprazole are both placed the first line antipsychotics. These two antipsychotics have different pharmacological effects. We investigated the effects of risperidone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4hydroxyphenylglycol after unsuccessful aripiprazole treatment in acute schizophrenia. Ten Japanese patients with acute schizophrenia were enrolled to this study. Plasma levels of monoamine metabolites were analyzed with high-performance liquid chromatography with electrochemical detection. Risperidone improved the symptoms and 4 of 10 patients were responders. Risperidone showed a tendency to decrease plasma HVA (pHVA) levels in responders (p = 0.068), but not in non-responders (p = 1.0). At baseline, pHVA levels of responders were significantly higher than that of non-responders (p = 0.033). A trend for negative correlation was found between pHVA at baseline and the changes in Positive and Negative Syndrome Scale-Total (p = 0.061, r = -0.61). Our results suggest that high pHVA level before switching may predict good response to the second line antipsychotics after unsuccessful first antipsychotic treatment. If aripiprazole is not effective in acute schizophrenia, switching to risperidone may be effective and reasonable strategy for improving symptoms. Copyright © 2012 John Wiley & Sons, Ltd.

Leukapheresis treatment in elderly acute leukemia patients with hyperleukocytosis: A single center experience.

PubMed

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Gozukara Bag, Harika; Nizam, Ilknur; Koroglu, Mustafa; Yigit, Ali; Ozgul, Mustafa

2016-02-01

Leukapheresis is an invasive treatment modality used for hyperleukocytosis. Various drugs and fluids are used during the leukapheresis. Aging itself and associated factors such as increased comorbidity, decreased tolerance to drugs, increased drug toxicity give rise to the application of other treatment modalities in elderly patients. Treatment of acute leukemia in the elderly differs from young patients. Consequently, we assumed that outcome, effectiveness, and side effects of leukapheresis treatment used for acute leukemia patients with hyperleukocytosis may be different in elderly compared to younger patients. We retrospectively evaluated a total of 39 patients. Eighteen patients were 65 years and older. Indications for leukapheresis were determined as symptoms of leukostasis and prophylaxis. Acid citrate dextrose-A, calcium gluconate, and plasma were used during the leukapheresis. Age, sex, diagnosis, count, and indications of leukapheresis procedures, leukocyte count, and lactate dehydrogenase level were analyzed at the onset of and after leukapheresis; side effects, causes of death, early and total mortality rates were also analyzed. We compared the two groups with regard to effectiveness, clinical outcomes, and side effects. There were no statistically significant differences between the two groups with respect to sex, diagnosis, initial leukocyte count, lactate dehydrogenase level, number of leukapheresis procedures, rates of side effects, or early and total mortality (P > 0.05). Leukapheresis treatment was effective in both groups (P < 0.05) and no significant difference was found in its effectiveness between two groups (P > 0.05). Leukapheresis is an effective and safe treatment modality in elderly acute leukemia patients with hyperleukocytosis. © 2015 Wiley Periodicals, Inc.

Comparative study to investigate the effect of meloxicam or minocycline HCl in situ gel system on local treatment of periodontal pockets.

PubMed

Kassem, Abeer Ahmed; Ismail, Fatma Ahmed; Naggar, Vivian Fahim; Aboulmagd, Elsayed

2014-08-01

In situ gelling formulations allow easy application to the target area. Gelation is induced by physiological stimuli at the site of application where the formula attains semisolid properties and exerts sustained drug release. In situ gelling formulations containing either 3% meloxicam (Mx) or 2% minocycline HCl (MH) were prepared for local application into the periodontal pockets. Gel formulations were based on the thermosensitive Pluronic(®) (Pl) and the pH-sensitive Carbopol(®) (C) polymers. C gels were prepared in combination with HPMC (H) to decrease its acidity. The total percent drug released from Pl formulae was 21.72% after 1 week for Mx and 85% after 3 days for MH. Their release kinetics data indicated anomalous non-Fickian behavior that could be controlled by both diffusion and chain relaxation. Addition of MH to C/H gels (1:2.5) resulted in liquefaction, followed by drug precipitation. Regarding C/H gel containing Mx, it showed a prolonged release rate up to 7 days with an initial burst effect; the kinetics data revealed Fickian-diffusion mechanism. The in vitro antibacterial activity studies for MH gel in Pl revealed that the drug released exceeded the minimum inhibitory concentration (MIC) of MH against Staphylococcus aureus ATCC 6538; placebo gel showed no effect on the microorganism. Clinical evaluation of Pl gels containing either Mx or MH showed significant improvement in chronic periodontitis patients, manifested by decrease in pocket depth and gingival index and increase in bone density.

Influence of acute treatment with sibutramine on the sympathetic neurotransmission of the young rat vas deferens.

PubMed

de Souza, Bruno Palmieri; da Silva, Edilson Dantas; Jurkiewicz, Aron; Jurkiewicz, Neide Hyppolito

2014-09-05

The effects of acute treatment with sibutramine on the peripheral sympathetic neurotransmission in vas deferens of young rats were still not evaluated. Therefore, we carried out this study in order to verify the effects of acute sibutramine treatment on the neuronal- and exogenous agonist-induced contractions of the young rat vas deferens. Young 45-day-old male Wistar rats were pretreated with sibutramine 6 mg/kg and after 4h the vas deferens was used for experiment. The acute treatment with sibutramine was able to increase the potency (pD2) of noradrenaline and phenylephrine. Moreover, the efficacy (Emax) of noradrenaline was increased while the efficacy of serotonin and nicotine were decreased. The maximum effect induced by a single concentration of tyramine was diminished in the vas deferens from treated group. Moreover, the leftward shift of the noradrenaline curves promoted by uptake blockers (cocaine and corticosterone) and β-adrenoceptor antagonist (propranolol) was reduced in the vas deferens of treated group. The initial phasic and secondary tonic components of the neuronal-evoked contractions of vas deferens from treated group at the frequencies of 2 Hz were decreased. Moreover, only the initial phasic component at 5 Hz was diminished by the acute treatment with sibutramine. In conclusion, we showed that the acute treatment with sibutramine in young rats was able to affect the peripheral sympathetic nervous system by inhibition of noradrenaline uptake and reduction of the neuronal content of this neurotransmitter, leading to an enhancement of vas deferens sensitivity to noradrenaline. Copyright © 2014 Elsevier B.V. All rights reserved.

Family centered brief intensive treatment: a pilot study of an outpatient treatment for acute suicidal ideation.

PubMed

Anastasia, Trena T; Humphries-Wadsworth, Terresa; Pepper, Carolyn M; Pearson, Timothy M

2015-02-01

Family Centered Brief Intensive Treatment (FC BIT), a hospital diversion treatment program for individuals with acute suicidal ideation, was developed to treat suicidal clients and their families. Individuals who met criteria for hospitalization were treated as outpatients using FC BIT (n = 19) or an intensive outpatient treatment without the family component (IOP; n = 24). Clients receiving FC BIT identified family members or supportive others to participate in therapy. FC BIT clients had significantly greater improvement at the end of treatment compared to IOP clients on measures of depression, hopelessness, and suicidality. Further research is needed to test the efficacy of FC BIT. © 2014 The American Association of Suicidology.

The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review.

PubMed

Gebremedhn, Endale Gebreegziabher; Shortland, Peter John; Mahns, David Anthony

2018-04-12

Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction and treatment cessation following the first dose of oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk factor for chronic neuropathy. However, there is underreporting of these parameters during the acute phase (≤ 14 days). This paper systematically reviews the incidence of acute OXIPN and its impact on treatment in the first cycle. A systematic literature search was performed using PubMed and Medline. Published original articles were included if they described details about prevalence of oxaliplatin-induced acute neuropathy. Fourteen studies, comprised of 6211 patients were evaluated. The majority of patients were treated with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most studies used the National Cancer Institute Common Toxicity Criteria to assess acute neuropathy. Acute neuropathy (Grades 1-4) was the most common event with prevalence ranging from 4-98%, followed by haematological (1.4-81%) and gastrointestinal (1.2-67%) toxicities, respectively. Drug regimens, starting dose of oxaliplatin and neuropathy assessment tools varied across studies. In addition, moderate to severe toxicities were common in patients that received a large dose of oxaliplatin (> 85 mg/m 2 ) and/ or combined drugs. The majority of studies did not report the factors affecting acute neuropathy namely the range (minimal) doses required to evoke acute neuropathy, patient and clinical risk factors. In addition, there was no systematic reporting of the number of patients subjected to prolonged infusion, dose reduction, treatment delay and treatment cessation during the acute phase. Despite the heterogeneity of studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment tools and study design, a large number of patients developed acute

Acute migraine: Current treatment and emerging therapies.

PubMed

Kalra, Arun A; Elliott, Debra

2007-06-01

Migraine is a common disabling primary headache disorder. Despite the need for a perfect treatment of this debilitating condition, the ideal "cure" eludes us. In 1992, the first triptan was released in the US for use in acute migraine. Triptans are more specific for the serotonin receptor 5-hydroxy triptamine (5-HT) 1 than previously prescribed drugs, such as ergotamines, with fewer side effects. This was an important first step in specific acute migraine therapy. Today however, triptans continue to be underutilized. There remains a concern, among practitioners and patients, about possible cardiovascular safety issues, despite the lack of strong evidence of serious adverse events. In fact, triptans now have a safe track record over more than a decade of use. Other perceived downfalls to use, include cost and variable efficacy. The more we learn about the clinical features and pathophysiology of migraine, the closer we are to finding a satisfactory monotherapy. Until then, recognizing that mixed mechanisms underlie migraine symptoms, rational polytherapy can be useful. Research on the roles of serotonin, calcitonin gene related peptide, glutamine and N-methyl-D-aspartate in the trigeminovascular system holds promise for those searching for the perfect migraine headache cure.

A model for dual disorder treatment in acute psychiatry in a VA population.

PubMed

Ahrens, M P

1998-01-01

One model for addressing the dual disorders of substance abuse and a concomitant mental disorder in an acute-psychiatry inpatient ward of a VA Medical Center utilized psychoeducation and ward policies to empower patients to make decisions affecting their recoveries. Existing staff shared responsibilities for implementing activities and creating ward milieu that supported psychiatric patients toward a life free of alcohol and drugs as they gained in acceptance of responsibility for the management of their mental disorders. Integrated programming assisted patients in constructing a meaningful path of recovery out of multiple treatment approaches and philosophies. Treatment principles, ward policies, and goals for an integrated acute-psychiatry model evolved over 4 years. Designed from a consumer-oriented "strengths perspective," patients responded to the new programming with satisfaction and gratitude. Recent adaptation of these policies, principles, and goals to a newly instituted continuous-care treatment program indicates the appropriateness of their application for outpatient dual disorder treatment and programming as well.

Risk profile and treatment options of acute ischemic in-hospital stroke.

PubMed

Schürmann, Kolja; Nikoubashman, Omid; Falkenburger, Björn; Tauber, Simone C; Wiesmann, Martin; Schulz, Jörg B; Reich, Arno

2016-03-01

Despite the potential immediate access to diagnosis and care, in-hospital stroke (IHS) is associated with delay in diagnosis, lower rates of reperfusion treatment, and unfavorable outcome. Endovascular reperfusion therapy has shown promising results in recent trials for community-onset strokes (COS) and is limited by less contraindications than systemic thrombolysis. Thus, endovascular approaches may offer additional acute treatment options for IHS. We performed a retrospective, observational monocentric analysis of patients with acute ischemic stroke between January 2010 and December 2014. Out of 3506 acute ischemic strokes, 331 (9.4%) were IHS. In-hospital mortality (31.4 vs. 8.0%) and duration of stay after stroke (19.5 vs. 12.1 days) were higher in IHS than in COS. Most IHS occurred in cardiologic and cardiosurgical patients after catheterization or surgery. In 111 cases (33.5%) the time of onset could not be established as a result of sedation or delayed referral resulting in delayed symptom recognition. 52 IHS (15.7%) and 828 COS (26.0%, p < 0.001) patients received any kind of reperfusion therapy, of which 59.6% (IHS) and 12.1% (COS) comprised isolated endovascular interventions (p < 0.001). Intra-hospital delays (time to brain imaging, systemic thrombolysis, and angiography) were longer and outcome parameters (mRS d90, in-hospital mortality, length of stay) were worse in IHS, whereas rates of procedural complications and intracranial hemorrhages were similar in both groups. The overall rate of reperfusion treatment is lower in IHS compared to COS, as IHS patients are less likely to be eligible for systemic thrombolysis. Interventional stroke treatment is a safe and feasible therapeutic option for patients who are not eligible for systemic thrombolysis and should be anticipated whenever IHS is diagnosed.

Validity of Sudden Gains in Acute Phase Treatment of Depression

ERIC Educational Resources Information Center

Vittengl, Jeffrey R.; Clark, Lee Anna; Jarrett, Robin B.

2005-01-01

The authors examined the validity of sudden gains identified with T. Z. Tang and R. J. DeRubeis's (1999) method in 2 clinical data sets that involved treatment of major depressive disorder (N=227). Sudden gains replicated among self- and clinician reports of depressive symptoms and predicted better psychosocial functioning at the acute phase…

Management of acute cough by Zataria multiflora Boiss as an alternative treatment.

PubMed

Mahboubi, Mohaddese

2018-01-01

Cough, as a defensive reflux mechanism, removes foreign objects and secretions from bronchi and bronchioles of airways. Zataria multiflora is a popular plant for treatment of cough in Iranian traditional medicine. The aim of this review was to evaluate the potency of Z. multiflora as an alternative treatment in management of acute cough and its possible mechanisms of action. Here the authors compiled information about Z. multiflora in the treatment of cough from all accessible resources and books. The results of this investigation showed that there were five clinical studies that evaluated the efficacy of Z. multiflora essential oil or extract alone (n = 1), in combination with Althaea officinalis (n = 2) or Foeniculum vulgare essential oil (n = 1), in the form of syrup (n = 3), oral drop (n = 1) and soft capsule (n = 1), for the treatment of acute cough in comparison with placebo or synthetic drugs (bromhexine, dextromethorphan and clobutinol). All clinical studies confirmed the efficacy of Z. multiflora in the amelioration of acute cough in pediatric (n = 1) and adult patients (n = 4) without any adverse effects. Different mechanisms, such as anti-inflammatory, analgesic, antimicrobial, relaxant and immune-enhancement, may be responsible for the efficacy of Z. multiflora in cough relief. Other clinical trials can be performed with Z. multiflora in combination with ivy leaf extract or primrose root extract on patients with cough. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Admission Glucose and Effect of Intra-Arterial Treatment in Patients With Acute Ischemic Stroke.

PubMed

Osei, Elizabeth; den Hertog, Heleen M; Berkhemer, Olvert A; Fransen, Puck S S; Roos, Yvo B W E M; Beumer, Debbie; van Oostenbrugge, Robert J; Schonewille, Wouter J; Boiten, Jelis; Zandbergen, Adrienne A M; Koudstaal, Peter J; Dippel, Diederik W J

2017-05-01

Hyperglycemia on admission is common after ischemic stroke. It is associated with unfavorable outcome after treatment with intravenous thrombolysis and after intra-arterial treatment. Whether hyperglycemia influences the effect of reperfusion treatment is unknown. We assessed whether increased admission serum glucose modifies the effect of intra-arterial treatment in patients with acute ischemic stroke. We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose >7.8 mmol/L. The primary outcome measure was the adjusted common odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale at 90 days, estimated with ordinal logistic regression. Secondary outcome variable was symptomatic intracranial hemorrhage. We assessed treatment effect modification of hyperglycemia and admission serum glucose levels with multiplicative interaction factors and adjusted for prognostic variables. Four hundred eighty-seven patients were included. Mean admission serum glucose was 7.2 mmol/L (SD, 2.2). Fifty-seven of 226 patients (25%) randomized to intra-arterial treatment were hyperglycemic compared with 61 of 261 patients (23%) in the control group. The interaction of either hyperglycemia or admission serum glucose levels and treatment effect on modified Rankin Scale scores was not significant ( P =0.67 and P =0.87, respectively). The same applied for occurrence of symptomatic hemorrhage ( P =0.39 for hyperglycemia, P =0.39 for admission serum glucose). We found no evidence for effect modification of intra-arterial treatment by admission serum glucose in patients with acute ischemic stroke. URL: www.isrctn.com. Unique identifier: ISRCTN10888758. © 2017 American Heart Association, Inc.

Efficacy and safety of parecoxib in the treatment of acute renal colic: a randomized clinical trial.

PubMed

Glina, Sidney; Damiao, Ronaldo; Afif-Abdo, Joao; Santa Maria, Carlos Francisco; Novoa, Raúl; Cairoli, Carlos Eurico Dornelles; Wajsbrot, Dalia; Araya, Gaston

2011-01-01

Although non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and opioids are effective treatments for acute renal colic, they are associated with adverse events (AEs). As cyclooxygenase-2 selective NSAIDs may provide a safer alternative, we compared the efficacy and safety of parecoxib versus an nsNSAID in subjects with acute renal colic. Phase IV., multicenter, double-blind, noninferiority, active-controlled study: 338 subjects with acute renal colic were randomized to parecoxib 40 mg i.v. plus placebo (n = 174) or ketoprofen 100 mg IV plus placebo (n = 164). 338 subjects with acute renal colic were randomized to parecoxib 40 mg IV (n = 174) or ketoprofen 100 mg IV(n = 164) plus placebo. Subjects were evaluated 15, 30, 45, 60, 90 and 120 minutes after treatment start and 24 hours after discharge. Primary endpoint was the mean pain intensity difference (PID) at 30 minutes by visual analog scale (VAS) (per-protocol population). An ANCOVA model was used with treatment group, country, and baseline score as covariates. Non-inferiority of parecoxib to ketoprofen was declared if the lower bound of the 95% confidence interval (CI) for the difference between the two groups excluded the pre-established margin of 10 mm for the primary endpoint. Baseline demographics were similar. The mean (SD) mPID30 min was 33.84 (24.61) and 35.16 (26.01) for parecoxib and ketoprofen, respectively. For treatment difference (parecoxib-ketoprofen) the lower bound of the 95% CI was 6.53. The mean change from baseline in VAS 30 minutes after study medication was ~43 mm; AEs were comparable between treatments. Parecoxib is as effective as ketoprofen in the treatment of pain due to acute renal colic, is well tolerated, and has a comparable safety profile.

Treatment and prevention of acute and recurrent ankle sprain: an overview of systematic reviews with meta-analysis.

PubMed

Doherty, Cailbhe; Bleakley, Chris; Delahunt, Eamonn; Holden, Sinead

2017-01-01

Ankle sprains are highly prevalent with high risk of recurrence. Consequently, there are a significant number of research reports examining strategies for treating and preventing acute and recurrent sprains (otherwise known as chronic ankle instability (CAI)), with a coinciding proliferation of review articles summarising these reports. To provide a systematic overview of the systematic reviews evaluating treatment strategies for acute ankle sprain and CAI. Overview of intervention systematic reviews. Individuals with acute ankle sprain/CAI. The primary outcomes were injury/reinjury incidence and function. 46 papers were included in this systematic review. The reviews had a mean score of 6.5/11 on the AMSTAR quality assessment tool. There was strong evidence for bracing and moderate evidence for neuromuscular training in preventing recurrence of an ankle sprain. For the combined outcomes of pain, swelling and function after an acute sprain, there was strong evidence for non-steroidal anti-inflammatory drugs and early mobilisation, with moderate evidence supporting exercise and manual therapy techniques. There was conflicting evidence regarding the efficacy of surgery and acupuncture for the treatment of acute ankle sprains. There was insufficient evidence to support the use of ultrasound in the treatment of acute ankle sprains. For the treatment of acute ankle sprain, there is strong evidence for non-steroidal anti-inflammatory drugs and early mobilisation, with moderate evidence supporting exercise and manual therapy techniques, for pain, swelling and function. Exercise therapy and bracing are supported in the prevention of CAI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Beneficial Effect of Beraprost Sodium Plus Aspirin in the Treatment of Acute Ischemic Stroke.

PubMed

Chen, Siqia; Xie, Sisi; He, Wenzhen; Wei, Duncan; Li, Shunxian; Chen, Wenjie

2017-09-12

BACKGROUND To investigate the combination of beraprost sodium (BPS) and aspirin in the treatment of acute ischemic stroke (AIS). MATERIAL AND METHODS 308 patients with acute cerebral infarction were randomly divided into two groups: experimental group (n=154), treated with BPS (40 μg, tid) and aspirin (100 mg, qd); control group (n=154), treated with 100 mg of aspirin, qd). The antiplatelet therapy remained unchangeable until six months after hospital discharge. RESULTS Initially, no significant differences were found between the two groups. After six months, the relapse-free survival rate was similar between the treatment group (98.1%) and the control group (97.4%). One patient died from AIS in the control group. However, glomerular filtration rate was significantly higher; neurological function and functional ability of patients were better in patients treated with BPS plus aspirin (experimental group) than that in aspirin alone group. No significant difference was found in the function of the coagulation system, suggesting that BPS plus aspirin treatment did not increase the risk of bleeding. Serious adverse events did not occur in both groups. Facial flushing (one case) and mild gastrointestinal reaction (one case) were found in the treatment group without influencing treatment. CONCLUSIONS In our trial involving patients with acute cerebral infarction, BPS plus aspirin was not found to be superior to aspirin in reducing the recurrence of cerebral infarction or death. However, BPS plus aspirin treatment could improve renal function and neurological function without increasing the risk of bleeding.

Early Prediction of Acute Antidepressant Treatment Response and Remission in Pediatric Major Depressive Disorder

ERIC Educational Resources Information Center

Tao, Rongrong; Emslie, Graham; Mayes, Taryn; Nakonezny, Paul; Kennard, Betsy; Hughes, Carroll

2009-01-01

The rate of symptom improvement during the early weeks of acute fluoxetine treatment is a good indicator of remission. This finding was made after evaluating the outcome of the fluoxetine treatment on 168 children and adults with depression.

A trial of high-dose, short-course levofloxacin for the treatment of acute bacterial sinusitis.

PubMed

Poole, Michael; Anon, Jack; Paglia, Margaret; Xiang, Jim; Khashab, Mohammed; Kahn, James

2006-01-01

Compare two dosage strengths of levofloxacin in the treatment of acute bacterial sinusitis. Multicenter clinical trial comparing levofloxacin 750 mg for 5 days vs levofloxacin 500 mg for 10 days. Sinus fluid samples were obtained by antral puncture (59.2%) or by sinus endoscopy (40.8%). Among microbiologically evaluable patients, 91.4% (139/152) of patients receiving levofloxacin 750 mg achieved clinical success vs 88.6% (132/149) of patients receiving levofloxacin 500 mg (95% CI -10.0, 4.2). Clinical success rates by pathogen were above 90% in both treatment groups for the 3 typical pathogens of acute sinusitis: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The safety profile of the 2 dosage strengths was similar. Levofloxacin 750 mg for 5 days is noninferior to levofloxacin 500 mg for 10 days. Levofloxacin 750 mg for 5 days represents a safe and effective treatment regimen for acute bacterial sinusitis. A-1b.

Filgrastim for the treatment of hematopoietic acute radiation syndrome.

PubMed

Farese, A M; MacVittie, T J

2015-09-01

The U.S. Food and Drug Administration (FDA) recently approved Neupogen(®) (filgrastim) for the treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident. It is the first medical countermeasure currently approved by the FDA for this indication under the criteria of the FDA "animal rule". This article summarizes the consequences of high-dose radiation exposure, a description of the hematopoietic acute radiation syndrome (H-ARS), the use of hematopoietic growth factors in radiation accident victims and current available treatments for H-ARS with an emphasis on the use of Neupogen in this scenario. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Diagnosis and treatment of acute ankle injuries: development of an evidence-based algorithm

PubMed Central

Polzer, Hans; Kanz, Karl Georg; Prall, Wolf Christian; Haasters, Florian; Ockert, Ben; Mutschler, Wolf; Grote, Stefan

2011-01-01

Acute ankle injuries are among the most common injuries in emergency departments. However, there are still no standardized examination procedures or evidence-based treatment. Therefore, the aim of this study was to systematically search the current literature, classify the evidence, and develop an algorithm for the diagnosis and treatment of acute ankle injuries. We systematically searched PubMed and the Cochrane Database for randomized controlled trials, meta-analyses, systematic reviews or, if applicable, observational studies and classified them according to their level of evidence. According to the currently available literature, the following recommendations have been formulated: i) the Ottawa Ankle/Foot Rule should be applied in order to rule out fractures; ii) physical examination is sufficient for diagnosing injuries to the lateral ligament complex; iii) classification into stable and unstable injuries is applicable and of clinical importance; iv) the squeeze-, crossed leg- and external rotation test are indicative for injuries of the syndesmosis; v) magnetic resonance imaging is recommended to verify injuries of the syndesmosis; vi) stable ankle sprains have a good prognosis while for unstable ankle sprains, conservative treatment is at least as effective as operative treatment without the related possible complications; vii) early functional treatment leads to the fastest recovery and the least rate of reinjury; viii) supervised rehabilitation reduces residual symptoms and re-injuries. Taken these recommendations into account, we present an applicable and evidence-based, step by step, decision pathway for the diagnosis and treatment of acute ankle injuries, which can be implemented in any emergency department or doctor's practice. It provides quality assurance for the patient and promotes confidence in the attending physician. PMID:22577506

Acute arsenic poisoning: absence of polyneuropathy after treatment with 2,3-dimercaptopropanesulphonate (DMPS).

PubMed Central

Moore, D F; O'Callaghan, C A; Berlyne, G; Ogg, C S; Davies, H A; House, I M; Henry, J A

1994-01-01

Two men aged 19 and 21 years ingested 1 g and 4 g respectively from 3 kg of a white crystalline powder that they thought was a substance of abuse. It was later identified as almost pure arsenic trioxide. Both had nausea and vomiting and one developed acute renal failure. Each was treated with 2,3-dimercaptopropanesulphonate (DMPS), and made a full recovery with no evidence of prolonged renal or neurological impairment. The DMPS-arsenic complex is probably associated with lower penetration into the CNS and as a consequence treatment with DMPS may result in lower acute and chronic neurotoxicity than treatment with the currently standard recommended chelating agent dimercaprol (British Anti-Lewisite; BAL). PMID:8089687

Twelve-month experience of acute stroke thrombolysis in Christchurch, New Zealand: emergency department screening and acute stroke service treatment.

PubMed

Fink, John

2005-05-06

To determine the safety and efficiency of an acute stroke thrombolysis service in a New Zealand public hospital setting. A 12-month audit of patients referred to the Christchurch Hospital Stroke Thrombolysis Service (STS) between 1 April 2002 and 31 March 2003 was undertaken. Sixty-one patients were referred to the STS during the study period, of whom 16 were treated with tissue plasminogen activator (t-PA). For treated patients, the median time from stroke onset to hospital presentation was 60 minutes, 'door-to-CT' time was 60 minutes, and the 'door-to-needle' time was 99 minutes. Minor protocol violations were recorded in two patients, but did not influence outcome. No patient was treated after 3 hours of stroke onset. Intracerebral haemorrhage occurred in two patients: one patient was significantly improved compared with pre-treatment status; a minor temporary deterioration occurred in the other patient. Eight of 16 patients had improved by 4 or more points on the NIH Stroke Scale Score at 24 hours. Acute stroke thrombolysis can be delivered safely and in accordance with internationally accepted guidelines using the Christchurch Hospital STS model of emergency department screening and acute stroke service treatment. Further improvements in performance of the STS remain possible.

[Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia].

PubMed

Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; García Valencia, Jenny; Jaramillo González, Luis Eduardo; de la Hoz, Ana María; Arenas, Álvaro; Tamayo Martínez, Nathalie

2014-01-01

To determine the efficacy and safety of different antipsychotic drugs in the management of patients diagnosed with schizophrenia in the acute phase. To formulate evidence-based recommendations on the antipsychotic (AP) drug management strategies for the treatment of the adult diagnosed with schizophrenia in the acute phase. Clinical practice guidelines were prepared, using the guidelines of the Methodology Guide of the Ministry of Health and Social Protection, in order to identify, synthesise, and evaluate the evidence and formulate recommendations as regards the management and follow-up of adult patients diagnosed with schizophrenia. The evidence of the NICE 82 guideline was adopted and updated, which answered the question on the management of the acute phase of adults with a diagnosis of schizophrenia. The evidence and its level were presented to the Guideline Development Group (GDG) in order to formulate recommendations following the methodology proposed by the GRADE approach. Clozapine, olanzapine, risperidone, ziprasidone, amisulpride, paliperidone, haloperidol, quetiapine, and aripiprazole were more effective than placebo for the majority of psychotic symptoms and the abandonment of treatment, but asenapine was not. Paliperidone, risperidone, quetiapine, clozapine, and olanzapine showed significant increases in weight compared to placebo. Haloperidol, risperidone, ziprasidone, and paliperidone had a higher risk of extrapyramidal symptoms than placebo. There was a significant risk of sedation or drowsiness with, risperidone, haloperidol, ziprasidone, quetiapine, olanzapine, and clozapine in the comparisons with placebo. Of the results of the comparisons between AP, it was shown that clozapine and paliperidone had a clinically significant effect compared to haloperidol and quetiapine, respectively. Olanzapine and risperidone had a lower risk of abandoning the treatment in general, and due to adverse reactions in two comparisons of each one, haloperidol was the

Different approaches to acute organophosphorus poison treatment.

PubMed

Nurulain, Syed Muhammad

2012-07-01

Organophosphorus compounds (OPCs) have a wide variety of applications and are a serious threat for self-poisoning, unintentional misuse, terrorist attack, occupational hazard and warfare attack. The present standard treatment has been reported to be unsatisfactory. Many novel approaches are being used and tested for acute organophosphorus (OP) poison treatment. The bioscavenger concept captured high attention among the scientific community during the last few decades. Other approaches like alkalinisation of blood plasma/serum and use of weak inhibitors against strong inhibitors, though it showed promising results, did not get such wide attention. The introduction of a novel broad-spectrum oxime has also been in focus. In this mini-review, an update of the overview of four different approaches has been discussed. The standard therapy that is atropine+oxime+benzodiazepine along with supportive measures will continue to be the best option with only the replacement of a single oxime to improve its broad-spectrum efficacy.

Relationship of Antibiotic Treatment to Recovery after Acute FEV1 Decline in Children with Cystic Fibrosis.

PubMed

Morgan, Wayne J; Wagener, Jeffrey S; Pasta, David J; Millar, Stefanie J; VanDevanter, Donald R; Konstan, Michael W

2017-06-01

Children with cystic fibrosis often experience acute declines in lung function. We previously showed that such declines are not always treated with antibiotics, but we did not assess whether treatment improves the likelihood of recovery. To determine whether new antibiotic treatment was associated with recovery from acute FEV 1 decline. We studied episodes of FEV 1 decline (≥10% from baseline) in the Epidemiologic Study of Cystic Fibrosis. Treatments were hospitalization, home intravenous antibiotic, new inhaled oral quinolone, or other oral antibiotic. We used logistic regression to evaluate whether treatment was associated with recovery to baseline or near baseline. Logistic regression of 9,875 patients showed that new antibiotic treatment was associated with an increased likelihood of recovery to 90% of baseline (P < 0.001), especially for hospitalization compared with no new antibiotic (odds ratio [OR], 2.79; 95% confidence interval, 2.41-3.23). All four outpatient treatments were associated with greater likelihood of recovery compared with no treatment (OR, 1.27-1.64). Inpatient treatment was better than outpatient treatment (OR, 1.94; 95% confidence interval, 1.68-2.23). Treatment-type ORs were similar across recovery criteria and levels of baseline lung function. New antibiotic therapy, and especially inpatient treatment, is associated with greater likelihood of recovery after acute decline in FEV 1 . Benefits extend across all disease stages and are especially important in patients with high lung function, who are at greatest risk for FEV 1 decline.

[Clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in treatment of acute paraquat poisoning].

PubMed

Zhao, Y; Jian, X D

2016-07-20

Objective: To investigate the clinical effect of compound monoammonium glycyrrhizinate combined with dandelion in the treatment of acute paraquat poisoning. Methods: A total of 80 patients with acute paraquat poisoning who were admitted to our hospital were enrolled as study subjects and randomly divided into routine treatment group (38 patients) and traditional Chinese medicine (TCM) group (42 patients) . The patients in the TCM group were given compound monoammonium glycyrrhizinate and dandelion in addition to the treatment in the control group. Serum alanine aminotransferase (ALT) , total bilirubin (TBil) , blood urea nitrogen (BUN) , creatinine (Cr) , and arterial blood lactate (Lac) and partial pressure of oxygen (PaO 2 ) during different time periods on day 3, 7, and 9 of treatment were observed in both groups, and ulceration of oral mucosa, pulmonary fibrosis, multiple organ dysfunction syndrome (MODS) , and mortality were compared between the two groups. Results: On days 3, 7, and 9 of treatment, the routine treatment group had significantly higher serum ALT, TBil, BUN, Cr, and arterial blood Lac than the TCM group. The routine treatment group had significantly lower arterial blood PaO 2 than the TCM group, while the TCM group had significantly lower incidence rates of ulceration of oral mucosa, pulmonary fibrosis, and MODS and a significantly lower mortality rate than the routine treatment group ( P <0.05) . Conclusion: In the treatment of patients with acute paraquat poisoning, compound monoammonium glycyrrhizinate combined with dandelion can effectively improve organ function, reduce the incidence of pulmonary fibrosis and MODS, improve the healing rate of oral ulcer, improve prognosis, and reduce mortality rate.

Acute Iliac Artery Rupture: Endovascular Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chatziioannou, A.; Mourikis, D.; Katsimilis, J.

The authors present 7 patients who suffered iliac artery rupture over a 2 year period. In 5 patients, the rupture was iatrogenic: 4 cases were secondary to balloon angioplasty for iliac artery stenosis and 1 occurred during coronary angioplasty. In the last 2 patients, the rupture was secondary to iliac artery mycotic aneurysm. Direct placement of a stent-graft was performed in all cases, which was dilated until extravasation was controlled. Placement of the stent-graft was successful in all the cases, without any complications. The techniques used, results, and mid-term follow-up are presented. In conclusion, endovascular placement of a stent-graft ismore » a quick, minimally invasive, efficient, and safe method for emergency treatment of acute iliac artery rupture, with satisfactory short- and mid-term results.« less

Acute otitis media: making sense of recent guidelines on antimicrobial treatment.

PubMed

Pichichero, Michael E; Casey, Janet R

2005-04-01

High-dose amoxicillin (80 to 90 mg/kg/d divided twice daily) remains the drug of choice for treatment of acute otitis media despite increasing antimicrobial resistance. For persistent or recurrent acute otitis media, guidelines recommend high-dose amoxicillin/clavulanate (90/6.4 mg/kg/d), cefdinir, cefprozil, cefpodoxime, cefuroxime, or ceftriaxone. Increasing the dose of amoxicillin does not cover infection with beta-lactamase-producing pathogens; add the beta-lactamase inhibitor clavulanate to amoxicillin, or choose a cephalosporin with good activity against S pneumoniae and good beta-lactamase stability. Key factors for enhancing compliance are taste of suspension, dosing frequency, and duration of therapy.

Treatment of acute periprosthetic infections with prosthesis retention: Review of current concepts.

PubMed

Kuiper, Jesse Wp; Willink, Robin Tjeenk; Moojen, Dirk Jan F; van den Bekerom, Michel Pj; Colen, Sascha

2014-11-18

Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty, occurring in approximately 1%-2% of all cases. With growing populations and increasing age, PJI will have a growing effect on health care costs. Many risk factors have been identified that increase the risk of developing PJI, including obesity, immune system deficiencies, malignancy, previous surgery of the same joint and longer operating time. Acute PJI occurs either postoperatively (4 wk to 3 mo after initial arthroplasty, depending on the classification system), or via hematogenous spreading after a period in which the prosthesis had functioned properly. Diagnosis and the choice of treatment are the cornerstones to success. Although different definitions for PJI have been used in the past, most are more or less similar and include the presence of a sinus tract, blood infection values, synovial white blood cell count, signs of infection on histopathological analysis and one or more positive culture results. Debridement, antibiotics and implant retention (DAIR) is the primary treatment for acute PJI, and should be performed as soon as possible after the development of symptoms. Success rates differ, but most studies report success rates of around 60%-80%. Whether single or multiple debridement procedures are more successful remains unclear. The use of local antibiotics in addition to the administration of systemic antibiotic agents is also subject to debate, and its pro's and con's should be carefully considered. Systemic treatment, based on culture results, is of importance for all PJI treatments. Additionally, rifampin should be given in Staphylococcal PJIs, unless all foreign material is removed. The most important factors contributing to treatment failure are longer duration of symptoms, a longer time after initial arthroplasty, the need for more debridement procedures, the retention of exchangeable components, and PJI caused by Staphylococcus (aureus or

Early investigational antibiotics for the treatment of acute exacerbations of chronic bronchitis.

PubMed

Falagas, Matthew E; Georgiou, Maria

2017-03-01

Acute exacerbations in patients with chronic bronchitis are a leading cause of hospitalizations and death. Bacteria contribute significantly to such exacerbations. The aim of this review was to explore the potential role of investigational antibiotics in the treatment of these episodes. Areas covered: The available literature in PubMed database, in websites related to investigational drugs and in websites of the producing companies has been searched. The in vitro activity against pathogens involved in acute exacerbations of chronic bronchitis and the pharmacokinetic profile of antibiotics currently under development were taken into consideration for inclusion in the review. Expert opinion: Several novel antimicrobial agents have completed preclinical and Phase I studies and were well-tolerated. Further investigation is mandatory in order to evaluate their future in treatment of chronic bronchitis exacerbations and discover potential advantages compared to already approved antimicrobials.

Role of somatostatin and its analogues in the treatment of acute and chronic pancreatitis.

PubMed Central

Büchler, M W; Binder, M; Friess, H

1994-01-01

Acute pancreatitis is caused by the activation of digestive enzymes in the pancreas and a possible treatment, therefore, is the inhibition of enzyme secretion. This approach is somewhat controversial, however, as it is not clear whether pancreatic secretion continues to occur during the course of acute pancreatitis. Animal studies show an appreciable reduction of secretion in the inflamed pancreas, but studies in humans are not conclusive. The use of somatostatin or its analogue, octreotide, has been investigated in several clinical studies. A meta analysis of six individual studies in which somatostatin was given for acute pancreatitis showed that somatostatin significantly reduces mortality. A trial in patients with moderate to severe acute pancreatitis showed a lower rate (although not statistically significant) of complications in patients treated with 3 x 200 and 3 x 500 micrograms/day octreotide, compared with controls and patients receiving a lower dose of octreotide. A further study showed a significant reduction in patient controlled analgesics in patients treated with octreotide compared with controls. Pain is the important clinical symptom of chronic pancreatitis, possibly resulting from an increased intraductal pressure during secretion. The effect on pain of the inhibition of pancreatic secretion by octreotide has been investigated in two studies. One showed no significant reduction in pain after treatment with octreotide for three days. In the other, in which octreotide was used for three weeks, significantly less pain and analgesic use was recorded during octreotide treatment than during placebo. The most common complication of chronic pancreatitis is the formation of pseudocysts. There is some evidence that octreotide may be useful in their treatment. PMID:7911442

Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels.

PubMed

Cigolini, Davide; Ricci, Giogio; Zannoni, Massimo; Codogni, Rosalia; De Luca, Manuela; Perfetti, Paola; Rocca, Giampaolo

2011-05-24

Clinical experience with hydroxocobalamin in acute cyanide poisoning via ingestion remains limited. This case concerns a 35-year-old mentally ill woman who consumed more than 20 apricot kernels. Published literature suggests each kernel would have contained cyanide concentrations ranging from 0.122 to 4.09 mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a raised pulse rate and slight metabolic acidosis. Forty minutes after admission (approximately 70 min postingestion), the patient experienced headache, nausea and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This prompted the administration of oxygen, which evoked a slight improvement in her vital signs. Hydroxocobalamin was then administered. After 24 h, she was completely asymptomatic with normalised blood pressure and other haemodynamic parameters. This case reinforces the safety and effectiveness of hydroxocobalamin in acute cyanide poisoning by ingestion.

Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels.

PubMed

Cigolini, Davide; Ricci, Giogio; Zannoni, Massimo; Codogni, Rosalia; De Luca, Manuela; Perfetti, Paola; Rocca, Giampaolo

2011-09-01

Clinical experience with hydroxocobalamin in acute cyanide poisoning via ingestion remains limited. This case concerns a 35-year-old mentally ill woman who consumed more than 20 apricot kernels. Published literature suggests each kernel would have contained cyanide concentrations ranging from 0.122 to 4.09 mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a raised pulse rate and slight metabolic acidosis. Forty minutes after admission (approximately 70 min postingestion), the patient experienced headache, nausea and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This prompted the administration of oxygen, which evoked a slight improvement in her vital signs. Hydroxocobalamin was then administered. After 24 h, she was completely asymptomatic with normalised blood pressure and other haemodynamic parameters. This case reinforces the safety and effectiveness of hydroxocobalamin in acute cyanide poisoning by ingestion.

Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

PubMed

He, William J; Zhong, Chongke; Xu, Tan; Wang, Dali; Sun, Yingxian; Bu, Xiaoqing; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Zhang, Jintao; Geng, Deqin; Zhang, Jianhui; Li, Dong; Li, Yongqiu; Yuan, Xiaodong; Zhang, Yonghong; Kelly, Tanika N

2018-06-01

We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P < 0.001 among subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups among subgroups. However, there was a significant interaction between antihypertensive treatment and baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. ClinicalTrials.gov Identifier: NCT01840072.

Acute and chronic fluid misdirection syndrome: pathophysiology and treatment.

PubMed

Grzybowski, Andrzej; Kanclerz, Piotr

2018-01-01

To summarize our current understanding of the specific pathogenic mechanisms of the fluid misdirection syndrome and possible treatment methods. We used the PubMed web platform to find relevant studies using the following keywords: infusion misdirection syndrome, aqueous misdirection syndrome, ciliary block, ciliovitreal block, capsular block, intraoperative fluid misdirection, subcapsular fluid entrapment, acute intraoperative rock-hard eye syndrome, positive vitreous pressure glaucoma, and malignant glaucoma. Other publications were also considered as a potential source of information when referenced in relevant articles. We collected and analyzed 55 articles dated from 1951 to 2016. Acute intraoperative rock-hard eye syndrome is characterized by a very shallow anterior chamber with the absence of suprachoroidal effusion or hemorrhage and no noticeable pathology of the iris-lens diaphragm. It usually occurs during uneventful phacoemulsification, particularly in hyperopic eyes. The pathophysiology of acute fluid misdirection syndrome is based on inappropriate movement of balanced salt solution via the zonular fibers. This syndrome has also been described as occurring from hours to months, or years, after the initial surgery. The pathophysiology of malignant glaucoma is based on similar mechanisms of cilio-lenticular block of aqueous flow leading to the misdirection of aqueous posteriorly into or besides the vitreous gel. Faced with these situations, vitreous decompression is required, preferably with hyaloido-capsulo-iridectomy. In phakic eyes, concomitant cataract extraction would be desirable. We believe both of these clinical conditions should be considered as one syndrome. We suggest the term acute fluid misdirection syndrome for the cascade of events during phacoemulsification surgery. Chronic fluid misdirection syndrome better describes the nature of malignant glaucoma.

[Acute confusional syndrome associated with obstructive sleep apnea aggravated by acidosis secondary to oral acetazolamide treatment].

PubMed

Miguel, E; Güell, R; Antón, A; Montiel, J A; Mayos, M

2004-06-01

Acute confusional syndrome, or delirium, is a transitory mental state characterized by the fluctuating alteration of awareness and attention levels. We present the case of a patient with acute confusional syndrome associated with obstructive sleep apnea syndrome (OSAS) aggravated by metabolic acidosis induced by oral acetazolamide treatment.A 70-year-old man with no history of neurological disease was referred with a clinical picture consistent with acute confusional syndrome presenting between midnight and dawn. During the admission examination infectious, toxic, and neurologic causes, or those related to metabolic or heart disease were ruled out. Arterial blood gases measured during one of the nighttime episodes of acute confusional syndrome showed mild hypoxia and hypercapnia with mixed acidosis. Signs and symptoms suggestive of OSAS had been developing over the months prior to admission, with snoring, sleep apnea, and moderate daytime drowsiness. Polysomnography demonstrated severe OSAS with an apnea-hypopnea index of 38. Mean arterial oxygen saturation was 83%; time oxygen saturation remained below 90% was 44%. The attending physician ordered the withdrawal of oral acetazolamide, which was considered the cause of the metabolic component of acidosis. Treatment with continuous positive airway pressure was initiated at 9 cm H2O, after a titration polysomnographic study. The patient continued to improve.OSAS, for which very effective treatment is available, should be included among diseases that may trigger acute confusional syndrome.

Treatment of Acute Periodontal Abscesses Using the Biofilm Decontamination Approach: A Case Report Study.

PubMed

Pini-Prato, Giovanpaolo; Magnani, Cristina; Rotundo, Roberto

2016-01-01

The aim of this preliminary study was to show the treatment effect of the biofilm decontamination approach on acute periodontal abscesses. Clinical cases showing acute periodontitis were treated using an oral tissue decontaminant material that contains a concentrated aqueous mixture of hydroxybenzenesulfonic and hydroxymethoxybenzene acids and sulfuric acid. The material was positioned into the pocket on the root surface and left in the site for 30 seconds. No instrumentation was performed before the treatment. No systemic or local antibiotics were used in any of the cases. A questionnaire was used for each patient to record the pain/discomfort felt when the material was administered. All of the treated cases healed well and very rapidly. The infections were quickly resolved without complications, and the pockets associated with marginal tissue recession were also reduced. The momentary pain upon introduction of the material was generally well tolerated in the nonsurgically treated cases, and it completely disappeared after a few seconds. The biofilm decontamination approach seems to be a very promising technique for the treatment of acute periodontal abscess. The local application of this material avoids the use of systemic or local antibiotics.

Novel immunotherapeutic approaches for the treatment of acute leukemia (myeloid and lymphoblastic)

PubMed Central

Ishii, Kazusa; Barrett, Austin J.

2016-01-01

There have been major advances in our understanding of the multiple interactions between malignant cells and the innate and adaptive immune system. While the attention of immunologists has hitherto focused on solid tumors, the specific immunobiology of acute leukemias is now becoming defined. These discoveries have pointed the way to immune interventions building on the established graft-versus-leukemia (GVL) effect from hematopoietic stem-cell transplant (HSCT) and extending immunotherapy beyond HSCT to individuals with acute leukemia with a diversity of immune manipulations early in the course of the leukemia. At present, clinical results are in their infancy. In the coming years larger studies will better define the place of immunotherapy in the management of acute leukemias and lead to treatment approaches that combine conventional chemotherapy, immunotherapy and HSCT to achieve durable cures. PMID:26834952

Acute migraine: Current treatment and emerging therapies

PubMed Central

Kalra, Arun A; Elliott, Debra

2007-01-01

Migraine is a common disabling primary headache disorder. Despite the need for a perfect treatment of this debilitating condition, the ideal “cure” eludes us. In 1992, the first triptan was released in the US for use in acute migraine. Triptans are more specific for the serotonin receptor 5-hydroxy triptamine (5-HT) 1 than previously prescribed drugs, such as ergotamines, with fewer side effects. This was an important first step in specific acute migraine therapy. Today however, triptans continue to be underutilized. There remains a concern, among practitioners and patients, about possible cardiovascular safety issues, despite the lack of strong evidence of serious adverse events. In fact, triptans now have a safe track record over more than a decade of use. Other perceived downfalls to use, include cost and variable efficacy. The more we learn about the clinical features and pathophysiology of migraine, the closer we are to finding a satisfactory monotherapy. Until then, recognizing that mixed mechanisms underlie migraine symptoms, rational polytherapy can be useful. Research on the roles of serotonin, calcitonin gene related peptide, glutamine and N-methyl-D-aspartate in the trigeminovascular system holds promise for those searching for the perfect migraine headache cure. PMID:18488069

WITHDRAWN: Immobilisation and functional treatment for acute lateral ankle ligament injuries in adults.

PubMed

Kerkhoffs, Gino M M J; Rowe, Brian H; Assendelft, Willem J J; Kelly, Karen D; Struijs, Peter A A; van Dijk, C N

2013-03-28

Acute lateral ankle ligament injuries (ankle sprains) are common problems in acute medical care. The treatment variation observed for the acutely injured lateral ankle ligament complex suggests a lack of evidence-based management strategies for this problem. The objective of this review was to assess the effectiveness of methods of immobilisation for acute lateral ankle ligament injuries and to compare immobilisation with functional treatment methods. We searched the Cochrane Bone, Joint and Muscle Trauma Group specialised register (December 2001); the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1966-May 2000), EMBASE (1988-May 2000), reference lists of articles, and contacted organisations and researchers in the field. Randomised and quasi-randomised controlled trials comparing either different types of immobilisation or immobilisation versus functional treatments for injuries to the lateral ligament complex of the ankle in adults were included. Trials which investigated the treatment of chronic instability or post-surgical treatment were excluded. Data were independently extracted by two authors. Where appropriate, results of comparable studies were pooled using fixed effects models. Individual and pooled statistics were reported as relative risks with 95% confidence intervals for dichotomous outcomes and weighted (WMD) or standardised (SMD) mean differences and 95% confidence intervals for continuous outcome measures. Heterogeneity between trials was tested using a standard chi-squared test. Twenty-one trials involving 2184 participants were included. The mean validity score of the included trials increased from 9.1 (SD 3.0) to 10 (SD 2.9) after retrieving further information (maximum 18 points). Statistically significant differences in favour of functional treatment when compared with immobilisation were found for seven outcome measures: more patients returned to sport in the long term (relative risk (RR) 1.86, 95

A randomized trial of intraarterial treatment for acute ischemic stroke.

PubMed

Berkhemer, Olvert A; Fransen, Puck S S; Beumer, Debbie; van den Berg, Lucie A; Lingsma, Hester F; Yoo, Albert J; Schonewille, Wouter J; Vos, Jan Albert; Nederkoorn, Paul J; Wermer, Marieke J H; van Walderveen, Marianne A A; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A; Lycklama à Nijeholt, Geert J; Boiten, Jelis; Brouwer, Patrick A; Emmer, Bart J; de Bruijn, Sebastiaan F; van Dijk, Lukas C; Kappelle, L Jaap; Lo, Rob H; van Dijk, Ewoud J; de Vries, Joost; de Kort, Paul L M; van Rooij, Willem Jan J; van den Berg, Jan S P; van Hasselt, Boudewijn A A M; Aerden, Leo A M; Dallinga, René J; Visser, Marieke C; Bot, Joseph C J; Vroomen, Patrick C; Eshghi, Omid; Schreuder, Tobien H C M L; Heijboer, Roel J J; Keizer, Koos; Tielbeek, Alexander V; den Hertog, Heleen M; Gerrits, Dick G; van den Berg-Vos, Renske M; Karas, Giorgos B; Steyerberg, Ewout W; Flach, H Zwenneke; Marquering, Henk A; Sprengers, Marieke E S; Jenniskens, Sjoerd F M; Beenen, Ludo F M; van den Berg, René; Koudstaal, Peter J; van Zwam, Wim H; Roos, Yvo B W E M; van der Lugt, Aad; van Oostenbrugge, Robert J; Majoie, Charles B L M; Dippel, Diederik W J

2015-01-01

In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset

Risk Factors for Failed Nonoperative Treatment and Rerupture in Acute Achilles Tendon Rupture.

PubMed

Reito, Aleksi; Logren, Hanna-Liina; Ahonen, Katri; Nurmi, Heikki; Paloneva, Juha

2018-01-01

Nonoperative treatment is feasible in most patients with acute Achilles tendon rupture. Risk factors associated with failed nonoperative treatment are poorly understood. We investigated risk factors associated with rerupture after nonoperative treatment and otherwise failed nonoperative treatment of Achilles tendon rupture. All patients diagnosed with acute Achilles tendon rupture between January 2009 and June 2016 and who underwent 8 weeks of nonoperative treatment with functional rehabilitation were included in the study. Patients with rerupture or otherwise failed nonoperative treatment were identified retrospectively. Time to rerupture and association of age, sex, time from injury, diabetes, and visits to the physiotherapist for cases of reruptures and otherwise failed nonoperative treatment were investigated. A total of 210 patients were included in the study. Fifteen patients sustained a rerupture. Rerupture incidence was 7.1%. Incidence of late reruptures, those occurring after return to daily activities at 12 weeks, was 1.9%. Six patients had otherwise failed nonoperative treatment. Median time to rerupture was 23 days (6 to 61) after the end of the treatment. The incidence of all-cause failure was 10.0%. Male gender was associated with reruptures ( P = .013) and failed nonoperative treatment for any reason ( P = .029). It is important to highlight the increased risk of rerupture in male patients during the first month after the end of the nonoperative treatment. Age alone, even in male patients, was a poor indication for operative treatment since it did not predict early failure. Further studies will hopefully clarify the influence of activity level on the risk of rerupture. Level IV, retrospective case series.

Unmet goals in the treatment of Acute Myocardial Infarction: Review