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Sample records for acute minocycline treatment

  1. Acute Minocycline Treatment Mitigates the Symptoms of Mild Blast-Induced Traumatic Brain Injury

    PubMed Central

    Kovesdi, Erzsebet; Kamnaksh, Alaa; Wingo, Daniel; Ahmed, Farid; Grunberg, Neil E.; Long, Joseph B.; Kasper, Christine E.; Agoston, Denes V.

    2012-01-01

    Mild traumatic brain injury (mTBI) represents a significant challenge for the civilian and military health care systems due to its high prevalence and overall complexity. Our earlier works showed evidence of neuroinflammation, a late onset of neurobehavioral changes, and lasting memory impairment in a rat model of mild blast-induced TBI (mbTBI). The aim of our present study was to determine whether acute treatment with the non-steroidal anti-inflammatory drug minocycline (Minocin®) can mitigate the neurobehavioral abnormalities associated with mbTBI, Furthermore, we aimed to assess the effects of the treatment on select inflammatory, vascular, neuronal, and glial markers in sera and in brain regions associated with anxiety and memory (amygdala, prefrontal cortex, ventral, and dorsal hippocampus) following the termination (51 days post-injury) of the experiment. Four hours after a single exposure to mild blast overpressure or sham conditions, we treated animals with a daily dose of minocycline (50 mg/kg) or physiological saline (vehicle) for four consecutive days. At 8 and 45 days post-injury, we tested animals for locomotion, anxiety, and spatial memory. Injured animals exhibited significantly impaired memory and increased anxiety especially at the later testing time point. Conversely, injured and minocycline treated rats’ performance was practically identical to control (sham) animals in the open field, elevated plus maze, and Barnes maze. Protein analyses of sera and brain regions showed significantly elevated levels of all of the measured biomarkers (except VEGF) in injured and untreated rats. Importantly, minocycline treatment normalized serum and tissue levels of the majority of the selected inflammatory, vascular, neuronal, and glial markers. In summary, acute minocycline treatment appears to prevent the development of neurobehavioral abnormalities likely through mitigating the molecular pathologies of the injury in an experimental model of mb

  2. Minocycline treatment reduces white matter damage after excitotoxic striatal injury.

    PubMed

    Guimarães, Joanilson S; Freire, Marco Aurelio M; Lima, Rafael R; Picanço-Diniz, Cristovam W; Pereira, Antonio; Gomes-Leal, Walace

    2010-05-01

    We investigated the protective effects of minocycline following white matter damage (WMD) in the rat striatum. Excitotoxic lesions were induced by N-Methyl-d-Aspartate (NMDA) microinjections and caused striatal damage, concomitant with microglial/macrophage activation. The excitotoxic lesion both damaged oligodendrocytes (Tau-1(+) cells) and caused a decrease in tissue reactivity for myelin basic protein (MBP) after post-lesional day 3 (PLD). Treatment with the semi-synthetic tetracycline antibiotic minocycline, however, led to oligodendrocyte preservation and decreased myelin impairment. Taken together, these results suggest that white matter damage (WMD) is an important component of the physiopathology of acute striatal damage and that microglial/macrophage activation contributes to this pathological phenomenon. PMID:20226770

  3. Electrocortical changes associated with minocycline treatment in fragile X syndrome

    PubMed Central

    Andrea, Schneider; Jacena, Leigh Mary; Patrick, Adams; Rawi, Nanakul; Tasleem, Chechi; John, Olichney; Randi, Hagerman; David, Hessl

    2016-01-01

    Minocycline normalizes synaptic connections and behavior in the knockout mouse model of fragile X syndrome (FXS). Human-targeted treatment trials with minocycline have shown benefits in behavioral measures and parent reports. Event-related potentials (ERPs) may provide a sensitive method of monitoring treatment response and changes in coordinated brain activity. Measurement of electrocortical changes due to minocycline was done in a double-blind, placebo-controlled crossover treatment trial in children with FXS. Children with FXS (Meanage 10.5 years) were randomized to minocycline or placebo treatment for 3 months then changed to the other treatment for 3 months. The minocycline dosage ranged from 25–100 mg daily, based on weight. Twelve individuals with FXS (eight male, four female) completed ERP studies using a passive auditory oddball paradigm. Current source density (CSD) and ERP analysis at baseline showed high-amplitude, long-latency components over temporal regions. After 3 months of treatment with minocycline, the temporal N1 and P2 amplitudes were significantly reduced compared with placebo. There was a significant amplitude increase of the central P2 component on minocycline. Electrocortical habituation to auditory stimuli improved with minocycline treatment. Our study demonstrated improvements of the ERP in children with FXS treated with minocycline, and the potential feasibility and sensitivity of ERPs as a cognitive biomarker in FXS treatment trials. PMID:23981511

  4. Minocycline-induced acute eosinophilic pneumonia: A case report and review of the literature☆

    PubMed Central

    Hung, Sharon W.

    2015-01-01

    Acute eosinophilic pneumonia (AEP) can be a challenging diagnosis and is often initially misdiagnosed as one of the more common pneumonia syndromes such as acute respiratory distress syndrome. Early bronchoalveolar lavage (BAL) is critical in distinguishing the diagnosis to initiate proper management. The etiology of AEP is unknown, though many drugs have been implicated, including minocycline. Minocycline is commonly used for pneumonia, acute bronchitis, urinary tract infections, and acne and is likely the cause of AEP in our patient. There are 26 case reports of minocycline-induced AEP. In most cases, outcomes were favorable and symptoms rapidly resolved upon discontinuation of minocycline, with 11 cases employing steroids, one case twelve hours of CPAP and another 5 days of intubation. None resulted in mortality. Although it is difficult to evaluate without further studies, steroids should be recommended for minocycline-induced AEP, especially for those with severe or persistent symptoms. PMID:26236618

  5. Combined treatment with atorvastatin and minocycline suppresses severity of EAE.

    PubMed

    Luccarini, Ilaria; Ballerini, Clara; Biagioli, Tiziana; Biamonte, Filippo; Bellucci, Arianna; Rosi, Maria Cristina; Grossi, Cristina; Massacesi, Luca; Casamenti, Fiorella

    2008-05-01

    Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of the central nervous system (CNS). An approach to improve MS treatment is to identify a rational combination of new medications or existing therapies that impact different aspects of the disease process. Statins are effective in the treatment of MS animal models and are promising candidates for future treatment. Minocycline ameliorates clinical severity of experimental autoimmune encephalomyelitis (EAE) and exhibits several anti-inflammatory and neuroprotective activities. In this study, we tested whether the combination of these two drugs could produce beneficial effects in EAE mice immunized with myelin oligodendrocyte protein (MOG). Our findings show that combined treatment, compared to using the medications alone, resulted in a significant reduction in disease severity, in both the acute and chronic phases of the disease, along with attenuation of inflammation, demyelination and axonal loss. Stereological analysis revealed that the combined treatment significantly guarded against neuroinflammation and neurodegeneration. Moreover, a significant suppression of anti-MOG antibody production in animals treated with the two medications was found. In conclusion, our findings prove that this combination of drugs is neuroprotective and suppresses the severity of EAE. Furthermore, this pharmacological approach appears to be promising as a future therapeutic strategy to control MS. PMID:18346732

  6. Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

    PubMed Central

    Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

    2013-01-01

    Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

  7. Extended-release Formulation of Minocycline in the Treatment of Moderate-to-severe Acne Vulgaris in Patients Over the Age of 12 Years

    PubMed Central

    2013-01-01

    Oral antibiotics continue to play an important role in the treatment of moderate-to-severe acne. Minocycline is widely used in moderate-to-severe acne. Minocycline has anti-inflammatory properties, activity against Propionibacterium acnes and lipophilicity. An extended-release formulation of minocycline has been introduced. Extended-release minocycline is not bioequivalent to nonmodified release minocycline products and exhibits dose-proportional pharmacokinetics. Food or dairy products did not influence absorption. Efficacy is not dose-dependent, while the incidence of acute vestibular adverse events increases with dose suggesting an optimal dose of 1mg/kg. In two Phase 3 clinical trials, mean percent improvement in inflammatory lesions after 12 weeks of treatment with extended-release minocycline was 43.1 and 45.8 percent compared to 31.7 and 30.8 percent with placebo (P=0.001 and P<0.001, respectively) while the incidence of acute vestibular adverse events was comparable to placebo. PMID:23882310

  8. 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…

  9. Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

    PubMed Central

    Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

    2015-01-01

    Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD. PMID:26174710

  10. Repurposing an Old Drug to Improve the Use and Safety of Tissue Plasminogen Activator for Acute Ischemic Stroke: Minocycline

    PubMed Central

    Hess, David C.; Fagan, Susan C.

    2015-01-01

    There is only 1 US Food and Drug Administration–approved drug for acute ischemic stroke: tissue plasminogen activator (tPA). Due to a short time window and fear of intracerebral hemorrhage (ICH), tPA remains underutilized. There is great interest in developing combination drugs to use with tPA to improve the odds of a favorable recovery and to reduce the risk of ICH. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for ICH associated with tPA use. Minocycline is also an anti-inflammatory agent and inhibits poly (ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in the clinical trials conducted to date. PMID:20410869

  11. Repurposing an old drug to improve the safety and use of tissue plasminogen activator for acute ischemic stroke: Minocycline

    PubMed Central

    Hess, David C; Fagan, Susan

    2014-01-01

    There is only 1 US Food and Drug Administration-approved drug for acute ischemic stroke: tissue plasminogen activator (tPA). Due to a short time window and fear of intracerebral hemorrhage (ICH), tPA remains underutilized. There is great interest in developing combination drugs to use with tPA to improve the odds of a favorable recovery and to reduce the risk of ICH. Minocycline is a broad spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for ICH associated with tPA use. Minocycline is also an anti-inflammatory agent and inhibits poly (ADP-ribose) polymerase- 1. Minocycline has been safe and well tolerated in the clinical trials conducted to date. PMID:20575623

  12. Minocycline-treatment of diabetic rats normalizes skin collagen production and mass: possible causative mechanisms.

    PubMed

    Schneir, M; Ramamurthy, N; Golub, L

    1990-05-01

    Daily minocycline-treatment of streptozotocin-induced diabetic rats not only prevented a diabetes-caused atrophy of skin collagen mass (10-mos old rats), but also normalized skin collagen mass to match that of growing (ca. 1%/d) non-diabetic controls (4- and 5-mos old rats). The causative mechanism by which minocycline-treatment normalizes skin collagen mass must, in part, be related to a general anabolic effect on growth (body weight) because the effect on skin collagen mass correlates strongly to that on body weight. Consequently, a minocycline-stimulated increase of a systemic factor (such as insulin-like growth factor) is not unlikely. The anabolic effect of minocycline-treatment of diabetic rats is also expressed as a normalized cellular ribosome mass (an index of total protein synthetic capacity) and a normalized absolute rate of collagen production. (Calculation of an absolute rate was justified by an apparent maximum saturation of the prolyl-tRNA pool(s) of skin, maximum saturation obtained by the pool-flooding approach). The normalized skin ribosome amount does not, however, explain a selective effect of minocycline-treatment on collagen production as opposed to that for non-collagen protein, this selective effect measured as relative collagen production. To explain such selectivity, the inhibition of diabetes-induced excess skin collagenase activity seems unlikely. (This inference is based on results from a preliminary study indicating that recently [less than 2 h] synthesized collagen is not degraded by the excess collagenase in skin of diabetic rats). Thus, the principal collagen fraction acted on by pathologically excess collagenase might be collagen at a later stage (greater than 2 h after synthesis) in its life cycle. (Another possibility for the selective effect of minocycline on collagen production, as yet untested, is reduced intracellular procollagen degradation.) Overall, this is the first study aimed at discerning the mechanism(s) by which

  13. Profile of minocycline and its potential in the treatment of schizophrenia

    PubMed Central

    Zhang, Lulu; Zhao, Jingping

    2014-01-01

    Accumulating evidence suggests that neuroinflammation affecting microglia plays an important role in the etiology of schizophrenia, and appropriate control of microglial activation may be a promising therapeutic strategy for schizophrenia. Minocycline, a second-generation tetracycline that inhibits microglial activation, has been shown to have a neuroprotective effect in various models of neurodegenerative disease, including anti-inflammatory, antioxidant, and antiapoptotic properties, and an ability to modulate glutamate-induced excitotoxicity. Given that these mechanisms overlap with neuropathologic pathways, minocycline may have a potential role in the adjuvant treatment of schizophrenia, and improve its negative symptoms. Here, we review the relevant studies of minocycline, ranging from preclinical research to human clinical trials. PMID:24971013

  14. Narrow-Band Ultraviolet B versus Oral Minocycline in Treatment of Unstable Vitiligo: A Prospective Comparative Trial

    PubMed Central

    Siadat, Amir Hossein; Zeinali, Naser; Iraji, Fariba; Abtahi-Naeini, Bahareh; Nilforoushzadeh, Mohammad Ali; Jamshidi, Kioumars; Khosravani, Parastoo

    2014-01-01

    Background. We have compared NB-UVB and oral minocycline in stabilizing vitiligo for the first time. Subjects and Methods. 42 patients were divided equally into two groups: the NB-UVB and minocycline groups. Phototherapy was administered twice a week on nonconsecutive days. In the minocycline group, patients were advised to take minocycline 100 mg once daily. The treatment period was 3 months. Vitiligo disease activity (VIDA) score was noted every 4 weeks for 12 months. Digital photographs were taken at baseline and monthly intervals. Results. Before the therapy, disease activity was present in 100% of the patients, which was reduced to 23.8% and 66.1% by the end of therapy in the NB-UVB and minocycline groups retrospectively (P < 0.05). 16 of the 21 (76/1%) patients with unstable disease in the NB-UVB group achieved stability, whereas this was the case for only 7 of the 21 (33.3%) in the minocycline group (P < 0.001). The diameter changes were statistically significant at the end of treatment in the NB-UVB group compared to the minocycline group (P = 0.031). Side effects in both groups were mild. Conclusion. NB-UVB was statistically more advantageous than oral minocycline in unstable vitiligo in terms of efficacy and the resulting stability. PMID:25221600

  15. Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

    SciTech Connect

    Huang, T.-Y.; Chu, H.-C.; Lin, Y.-L.; Lin, C.-K.; Hsieh, T.-Y.; Chang, W.-K.; Chao, Y.-C.; Liao, C.-L.

    2009-05-15

    In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitric oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.

  16. 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. PMID:27449540

  17. Minocycline Oral

    MedlinePlus

    ... this medication.be aware that antacids, calcium supplements, iron products, and laxatives containing magnesium interfere with minocycline, making it less effective. Take minocycline 1 hour before ...

  18. Minocycline treatment ameliorates interferon-alpha- induced neurogenic defects and depression-like behaviors in mice

    PubMed Central

    Zheng, Lian-Shun; Kaneko, Naoko; Sawamoto, Kazunobu

    2015-01-01

    Interferon-alpha (IFN-α) is a proinflammatory cytokine that is widely used for the treatment of chronic viral hepatitis and malignancy, because of its immune-activating, antiviral, and antiproliferative properties. However, long-term IFN-α treatment frequently causes depression, which limits its clinical utility. The precise molecular and cellular mechanisms of IFN-α-induced depression are not currently understood. Neural stem cells (NSCs) in the hippocampus continuously generate new neurons, and some evidence suggests that decreased neurogenesis plays a role in the neuropathology of depression. We previously reported that IFN-α treatment suppressed hippocampal neurogenesis and induced depression-like behaviors via its receptors in the brain in adult mice. However, it is unclear how systemic IFN-α administration induces IFN-α signaling in the hippocampus. In this study, we analyzed the role of microglia, immune cells in the brain, in mediating the IFN-α-induced neurogenic defects and depressive behaviors. In vitro studies demonstrated that IFN-α treatment induced the secretion of endogenous IFN-α from microglia, which suppressed NSC proliferation. In vivo treatment of adult mice with IFN-α for 5 weeks increased the production of proinflammatory cytokines, including IFN-α, and reduced neurogenesis in the hippocampus. Both effects were prevented by simultaneous treatment with minocycline, an inhibitor of microglial activation. Furthermore, minocycline treatment significantly suppressed IFN-α-induced depressive behaviors in mice. These results suggest that microglial activation plays a critical role in the development of IFN-α-induced depression, and that minocycline is a promising drug for the treatment of IFN-α-induced depression in patients, especially those who are low responders to conventional antidepressant treatments. PMID:25674053

  19. Local delivery of minocycline-loaded PEG-PLA nanoparticles for the enhanced treatment of periodontitis in dogs

    PubMed Central

    Yao, Wenxin; Xu, Peicheng; Pang, Zhiqing; Zhao, Jingjing; Chai, Zhilan; Li, Xiaoxia; Li, Huan; Jiang, Menglin; Cheng, Hongbo; Zhang, Bo; Cheng, Nengneng

    2014-01-01

    Background Rapid local drug clearance of antimicrobials is a major drawback for the treatment of chronic periodontitis. In the study reported here, minocycline-loaded poly(ethylene glycol)-poly(lactic acid) nanoparticles were prepared and administered locally for long drug retention and enhanced treatment of periodontitis in dogs. Methods Biodegradable poly(ethylene glycol)-poly(lactic acid) was synthesized to prepare nanoparticles using an emulsion/solvent evaporation technique. The particle size and zeta potential of the minocycline-loaded nanoparticles (MIN-NPs) were determined by dynamic light scattering and the morphology of the nanoparticles was observed by transmission electron microscopy. The in vitro release of minocycline from MIN-NPs and in vivo pharmacokinetics of minocycline in gingival crevice fluid, after local administration of MIN-NPs in the periodontal pockets of beagle dogs with periodontitis, were investigated. The anti-periodontitis effects of MIN-NPs on periodontitis-bearing dogs were finally evaluated. Results Transmission electron microscopy examination and dynamic light scattering results revealed that the MIN-NPs had a round shape, with a mean diameter around 100 nm. The in vitro release of minocycline from MIN-NPs showed a remarkably sustained releasing characteristic. After local administration of the MIN-NPs, minocycline concentration in gingival crevice fluid decreased slowly and retained an effective drug concentration for a longer time (12 days) than Periocline®. Anti-periodontitis effects demonstrated that MIN-NPs could significantly decrease symptoms of periodontitis compared with Periocline and minocycline solution. These findings suggest that MIN-NPs might have great potential in the treatment of periodontitis. PMID:25170266

  20. Cytotoxic Effects of Tetracycline Analogues (Doxycycline, Minocycline and COL-3) in Acute Myeloid Leukemia HL-60 Cells

    PubMed Central

    Maguire, Kim R.; Sidén, Åke; Potácová, Zuzana

    2014-01-01

    Tetracycline analogues (TCNAs) have been shown to inhibit matrix metalloproteinases and to induce apoptosis in several cancer cell types. In the present study, the cytotoxic effects of TCNAs doxycycline (DOXY), minocycline (MINO) and chemically modified tetracycline-3 (COL-3) were investigated in the human acute myeloid leukemia HL-60 cell line. Cells were incubated with TCNAs in final concentrations of 0.5–100 µg/ml for 24 h. Viability of the leukemic cells was inhibited in a concentration-dependent manner using resazurin assay. The estimated IC50s were 9.2 µg/ml for DOXY, 9.9 µg/ml for MINO and 1.3 µg/ml for COL-3. All three TCNAs induced potent cytotoxic effects and cell death. Apoptosis, which was assessed by morphological changes and annexin V positivity, was concentration- and time-dependent following incubation with any one of the drugs. TCNAs induced DNA double strand breaks soon after treatment commenced as detected by γH2AX and western blot. The loss of mitochondrial membrane potential (Δψm), caspase activation and cleavage of PARP and Bcl-2 were observed; however, the sequence of events differed among the drugs. Pancaspase inhibitor Z-VAD-FMK improved survival of TCNAs-treated cells and decreased TCNAs-induced apoptosis. In summary, we demonstrated that TCNAs had a cytotoxic effect on the HL-60 leukemic cell line. Apoptosis was induced via mitochondria-mediated and caspase-dependent pathways in HL-60 cells by all three TCNAs. COL-3 exerted the strongest anti-proliferative and pro-apoptotic effects in concentrations that have been achieved in human plasma in reported clinical trials. These results indicate that there is a therapeutic potential of TCNAs in leukemia. PMID:25502932

  1. 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

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

    PubMed

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

    2014-11-01

    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

  3. Minocycline with aspirin: a therapeutic approach in the treatment of diabetic neuropathy.

    PubMed

    Bhatt, L K; Veeranjaneyulu, Addepalli

    2010-12-01

    Enhanced production of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in diabetes leads to degradation of extracellular matrix in blood vessels and leads to complications of diabetes. In the present study, we have targeted MMP-2 and MMP-9 overactivation in diabetic neuropathy using a known MMP-2 and MMP-9 inhibitor, minocycline, with a non-selective COX inhibitor, aspirin. Streptozotocin-induced diabetic neuropathy was carried out in male Wistar rats and monitored by measuring the sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), tail flick latency and hot plate latency. Three weeks of treatment with a combination of minocycline and aspirin showed significant improvement in SNCV, MNCV, hot plate latency and tail flick latency when compared with diabetic control. The results of the present study suggest that MMP-2 and MMP-9 inhibition in the presence of COX inhibitor prevents the development of experimental diabetic neuropathy in rats and can be a potential approach for the treatment. PMID:20213226

  4. Prevention of hypoglycemia-induced neuronal death by minocycline.

    PubMed

    Won, Seok Joon; Kim, Jin Hee; Yoo, Byung Hoon; Sohn, Min; Kauppinen, Tiina M; Park, Man-Seong; Kwon, Hyung-Joo; Liu, Jialing; Suh, Sang Won

    2012-01-01

    Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes neuronal death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae. Minocycline, a second-generation tetracycline derivative, has been recognized as an anti-inflammatory and neuroprotective agent in several animal models such as stroke and traumatic brain injury. In the present study, we tested whether minocycline also has protective effects on hypoglycemia-induced neuronal death and cognitive impairment. To test our hypothesis we used an animal model of insulin-induced acute hypoglycemia. Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose reperfusion and injected once per day for the following 1 week. Histological evaluation for neuronal death and microglial activation was performed from 1 day to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after hypoglycemia. Microglial activation began to be evident in the hippocampal area at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection significantly reduced hypoglycemia-induced microglial activation and myeloperoxidase (MPO) immunoreactivity. Neuronal death was significantly reduced by minocycline treatment when evaluated at 1 week after hypoglycemia. Hypoglycemia-induced cognitive impairment is also significantly prevented by the same minocycline regimen when subjects were evaluated at 6 weeks after hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours post-insult) with minocycline protects against microglial activation, neuronal death and cognitive impairment caused by severe hypoglycemia. The present study suggests that minocycline has therapeutic potential to prevent hypoglycemia-induced brain injury in diabetic patients. PMID:22998689

  5. 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. PMID:27291517

  6. Minocycline inhibits brain inflammation and attenuates spontaneous recurrent seizures following pilocarpine-induced status epilepticus.

    PubMed

    Wang, N; Mi, X; Gao, B; Gu, J; Wang, W; Zhang, Y; Wang, X

    2015-02-26

    Mounting evidence suggests that brain inflammation mediated by glial cells may contribute to epileptogenesis. Minocycline is a second-generation tetracycline and has potent antiinflammatory effects independent of its antimicrobial action. The present study aimed to investigate whether minocycline could exert antiepileptogenic effects in a rat lithium-pilocarpine model of temporal lobe epilepsy. The temporal patterns of microglial and astrocytic activation were examined in the hippocampal CA1 and the adjacent cortex following pilocarpine-induced status epilepticus (SE). These findings displayed that SE caused acute and persistent activation of microglia and astrocytes. Based on these findings, Minocycline was administered once daily at 45 mg/kg for 14 days following SE. Six weeks after termination of minocycline treatment, spontaneous recurrent seizures (SRS) were recorded by continuous video monitoring. Minocycline inhibited the SE-induced microglial activation and the increased production of interleukin-1β and tumor necrosis factor-α in the hippocampal CA1 and the adjacent cortex, without affecting astrocytic activation. In addition, Minocycline prevented the SE-induced neuronal loss in the brain regions examined. Moreover, minocycline significantly reduced the frequency, duration, and severity of SRS during the two weeks monitoring period. These results demonstrated that minocycline could mitigate SE-induced brain inflammation and might exert disease-modifying effects in an animal model of temporal lobe epilepsy. These findings offer new insights into deciphering the molecular mechanisms of epileptogenesis and exploring a novel therapeutic strategy for prevention of epilepsy. PMID:25541249

  7. Update on Acinetobacter species: mechanisms of antimicrobial resistance and contemporary in vitro activity of minocycline and other treatment options.

    PubMed

    Castanheira, Mariana; Mendes, Rodrigo E; Jones, Ronald N

    2014-12-01

    tetracycline HCL as a surrogate for the susceptibility other tetracyclines fails to detect minocycline-susceptible isolates and the potential utility of minocycline for the treatment of many MDR A. baumannii infections and other difficult-to-treat species, where there are often limited choices of antimicrobials. PMID:25371512

  8. The combination of morphine and minocycline may be a good treatment for intractable post-herpetic neuralgia.

    PubMed

    Chen, Suchang; Hui, Hui; Zhang, Deren; Xue, Yanzhi

    2010-12-01

    Post-herpetic neuralgia (PHN) is a devastating complication of shingles. The treatment of PHN with traditional pharmaceutical agents has various side effects. Therefore, the treatment of intractable PHN is often very time consuming, mainly because the available treatments often lead to intolerable side effects before the efficient dose can be reached. Opioids such as morphine and oxycodone are the most widely used drugs for the alleviation for severe chronic pain. A number of high quality studies demonstrated that opioids are effective in relieving neuropathic pain including PHN. Yet concerns of misuse, abuse and tolerance of opioids have, however, severely influenced their contribution to neuropathic pain, especially the tolerance that resulted in a loss of drug effect or the necessity for escalating doses to produce pain relief. The glia cells, particularly microglia and astrocytes are thought to play an important role in central sensitization. It is known that activated microglia cells produce NO, cytokines, and cyclooxygenase. All of these chemicals regulate synaptic transmissions in the central nervous system. Additionally, glia modulations showed antiallodynic and antihyperalgesic properties in various experimental pain models. Minocycline, a semisynthetic, second-generation tetracycline can potently inhibit microglial activation and proliferation. Also, the growing body of recent evidence indicates that minocycline attenuates morphine tolerance in neuropathic mice with a mechanism related to microglia. The combination of morphine and minocycline has synergetic effect. This can prevent the development of intractable PHN and attenuate morphine antinociceptive tolerance and further improve the efficacy of morphine and therefore reducing its dosage and side effects. We thereby hypothesize that the combination of morphine and minocycline may produce a duel effect of morphine antinociceptive and minocycline selectively inhibiting the activation of microglia. PMID

  9. 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. PMID:26718463

  10. Paclitaxel-induced hyposensitivity to nociceptive chemical stimulation in mice can be prevented by treatment with minocycline

    PubMed Central

    Masocha, Willias

    2014-01-01

    Development of peripheral neuropathy, which can present as painful neuropathy or loss of sensation, sometimes limit the use of paclitaxel in the treatment of solid tumors such as breast cancer. Previous studies reported development of thermal hyperalgesia in mice treated with paclitaxel. In this study an automated flinch detection system for the formalin test (20 μl of 5% formalin injected subcutaneously into the paw dorsum) was used to evaluate chemical nociception in BALB/c mice treated with paclitaxel 2 mg/kg alone or coadministered with minocycline 50 mg/kg, intraperitoneally for 5 consecutive days. Reaction latency to thermal stimuli (hot-plate) was also measured. Injection of formalin resulted in biphasic paw flinches; phase 1 (1–9 minutes) and phase 2 (10–40 minutes). Treatment with paclitaxel reduced cumulative flinches in both phases 1 and 2 by 28% and 43%, respectively at day 7. However, treatment with paclitaxel also induced thermal hyperalgesia. Co-administration of paclitaxel with minocycline prevented development of both paclitaxel-induced hyposensitivity to chemical nociception and thermal hyperalgesia. In conclusion, the results indicate paclitaxel induces chemical hyposensitivity and thermal hyperalgesia in mice. Minocycline protected against paclitaxel-induced chemical hyposensitivity and thermal hyperalgesia, thus, providing further support of the usefulness of the drug in prevention of chemotherapy-induced neuropathy. PMID:25335491

  11. Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice.

    PubMed

    Majidi, Jafar; Kosari-Nasab, Morteza; Salari, Ali-Akbar

    2016-01-01

    Neonatal infection is associated with increased lifetime risk for neuropsychiatric disorders including anxiety and depression, with evidence showing that dysregulation of the hypothalamic-pituitary-adrenal-(HPA)-axis system may be partly responsible. Preclinical and clinical studies demonstrate that minocycline exhibits antidepressant effects through inhibition of microglial activation and anti-inflammatory actions, and of interest is that recent studies suggest that minocycline alleviates the behavioral abnormalities induced by early-life insults. The current study was designed to determine if developmental minocycline treatment attenuates the neonatal immune activation-induced anxiety- and depression-like symptoms and HPA-axis-dysregulation later in life. To this end, neonatal mice were treated to either lipopolysaccharide or saline on postnatal days (PND) 3-5, then dams during lactation (PND 6-20) and male offspring during adolescence (PND 21-40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1β) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1β in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early

  12. Minocycline Ointment as a Local Drug Delivery in the Treatment of Generalized Chronic Periodontitis - A Clinical Study

    PubMed Central

    Abbas, Sara; Ari, Geetha

    2016-01-01

    Introduction The primary goal in periodontal therapy includes removal of the etiological factors by mechanical periodontal treatment, which sometimes fail to eliminate the anaerobic infection at the base of the pocket and requires adjuvant chemical therapy. Aim The aim of the study was to evaluate the effectiveness of 2% minocycline ointment when used as an adjunct to periodontal flap surgery and post-operative maintenance period for the treatment of generalized chronic periodontitis. Materials and Methods The study included 30 subjects comprising of 60 posterior sextants in a split mouth design in which 30 sextants were treated as experimental and 30 sextants as control with a probing pocket depth≥6mm. In Group A (experimental group) 30 sextants were treated with open flap debridement followed by the application of minocycline ointment as a local drug delivery. In Group B (control group) 30 sextants were treated with open flap debridement alone. Minocycline hydrochloride ointment was applied on the 0 day and 3rd month. The clinical parameters such as plaque index, probing pocket depth, clinical attachment level and gingival bleeding index were recorded at 0 day, 3rd month and 6th month in both the groups. Paired and unpaired t-test were used to compare the means of the two groups. Results When Group A and Group B were compared, Group A showed significantly greater reduction in gingival bleeding index, probing pocket depth and gain in clinical attachment level than Group B, from 0 day to 3 months and from 0 day to 6 months. Group A showed significant reduction in plaque index than Group B when they were compared at 6 months. Conclusion The results demonstrate that there was significant reduction in the clinical parameters with improvement in the periodontal status on application of minocycline ointment as an adjunct to periodontal flap surgery in generalized chronic periodontitis. PMID:27504402

  13. [Intravenous Minocycline and Levofloxacin for Treatment of Two Cases of Japanese Spotted Fever].

    PubMed

    Sato, Akihiro; Nakamura, Itaru; Ikeda, Hideki; Mizuno, Yasutaka; Fujii, Takeshi; Matsumoto, Tetsuya; Kanda, Tetsurou

    2015-09-01

    We report herein on two cases of Japanese spotted fever (JSF) treated with intravenous minocycline (MINO) and levofloxacin (LVFX). An 80 year-old woman (Case1) and a 63 year-old man (Case2) with high fever (> 39 degrees C) and wide-spread skin erythema were admitted because they were suspected of having developed JSF. After admission, we treated them with intravenous MINO and LVFX. The patients' fevers were resolved within 36 hours after antibiotics. They were diagnosed as having JSF based on the serological test, and Rickettsia japonica was detected from the genetic findings (PCR analysis from eschar) only in case 1. In the treatment of fulminant JSF (body temperature > 39 degrees C) the prompt administration of a combination of tetracycline and new quinolone has been recommended. The number of cases of JSF and its endemic area are gradually increasing in Japan. As for new quinolones, ciprofloxacin and tosufloxacin have been used against to JSF in Japan, but LVFX may become a new option. PMID:26630793

  14. Selected gene profiles of stressed NSC-34 cells and rat spinal cord following peripheral nerve reconstruction and minocycline treatment

    PubMed Central

    KEILHOFF, GERBURG; LUCAS, BENJAMIN; UHDE, KATJA; FANSA, HISHAM

    2016-01-01

    The present study was conducted to investigate the effects of minocycline on the expression of selected transcriptional and translational profiles in the rat spinal cord following sciatic nerve (SNR) transection and microsurgical coaptation. The mRNA and protein expression levels of B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, major histocompatibility complex I (MHC I), tumor necrosis factor-α (TNF-α), activating transcription factor 3 (ATF3), vascular endothelial growth factor (VEGF), matrix metalloproteinase 9 (MMP9), and growth associated protein-43 (GAP-43) were monitored in the rat lumbar spinal cord following microsurgical reconstruction of the sciatic nerves and minocycline treatment. The present study used semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. As a PCR analysis of spinal cord tissue enabled the examination of the expression patterns of all cell types including glia, the motorneuron-like NSC-34 cell line was used to investigate expression level changes in motorneurons. As stressors, oxygen glucose deprivation (OGD) and lipopolysaccharide (LPS) treatment were performed. SNR did not induce significant degeneration of ventral horn motorneurons, whereas microglia activation and synaptic terminal retraction were detectable. All genes were constitutively expressed at the mRNA and protein levels in untreated spinal cord and control cells. SNR significantly increased the mRNA expression levels of all genes, albeit only temporarily. In all genes except MMP9 and GAP-43, the induction was seen ipsilaterally and contralaterally. The effects of minocycline were moderate. The expression levels of MMP9, TNF-α, MHC I, VEGF, and GAP-43 were reduced, whereas those of Bax and Bcl-2 were unaffected. OGD, but not LPS, was toxic for NSC-34 cells. No changes in the expression levels of Bax, caspase-3, MHC I or ATF3 were observed. These results indicated that motorneurons were not

  15. Minocycline reduces ethanol drinking.

    PubMed

    Agrawal, R G; Hewetson, A; George, C M; Syapin, P J; Bergeson, S E

    2011-06-01

    Alcoholism is a disease characterized by continued alcohol consumption despite recurring negative consequences. Thus, medications that reduce the drive to consume alcohol can be beneficial in treating alcoholism. The neurobiological systems that regulate alcohol consumption are complex and not fully understood. Currently, medications are available to treat alcoholism that act either by causing accumulation of a toxic metabolite of ethanol, or by targeting specific transmitter receptors. The purpose of our study was to investigate a new potential therapeutic pathway, neuroimmune interactions, for effects on ethanol consumption. We hypothesized that neuroimmune activity of brain glia may have a role in drinking. We utilized minocycline, a second generation tetracycline antibiotic that has immune modulatory actions, to test our hypothesis because it is known to suppress microglia, and to a lesser extent astroglia, activity following many types of insults to the brain. Treatment with 50mg/kg minocycline significantly reduced ethanol intake in male and female C57Bl/6J mice using a free choice voluntary drinking model. Saline injections did not alter ethanol intake. Minocycline had little effect on water intake or body weight change. The underlying mechanism whereby minocycline reduced ethanol intake requires further study. The results suggest that drugs that alter neuroimmune pathways may represent a new approach to developing additional therapies to treat alcoholism. PMID:21397005

  16. 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. PMID:22526685

  17. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window.

    PubMed

    Yrjänheikki, J; Tikka, T; Keinänen, R; Goldsteins, G; Chan, P H; Koistinaho, J

    1999-11-01

    The only treatment of patients with acute ischemic stroke is thrombolytic therapy, which benefits only a fraction of stroke patients. Both human and experimental studies indicate that ischemic stroke involves secondary inflammation that significantly contributes to the outcome after ischemic insult. Minocycline is a semisynthetic second-generation tetracycline that exerts antiinflammatory effects that are completely separate from its antimicrobial action. Because tetracycline treatment is clinically well tolerated, we investigated whether minocycline protects against focal brain ischemia with a wide therapeutic window. Using a rat model of transient middle cerebral artery occlusion, we show that daily treatment with minocycline reduces cortical infarction volume by 76 +/- 22% when the treatment is started 12 h before ischemia and by 63 +/- 35% when started even 4 h after the onset of ischemia. The treatment inhibits morphological activation of microglia in the area adjacent to the infarction, inhibits induction of IL-1beta-converting enzyme, and reduces cyclooxygenase-2 expression and prostaglandin E(2) production. Minocycline had no effect on astrogliosis or spreading depression, a wave of ionic transients thought to contribute to enlargement of cortical infarction. Treatment with minocycline may act directly on brain cells, because cultured primary neurons were also salvaged from glutamate toxicity. Minocycline may represent a prototype of an antiinflammatory compound that provides protection against ischemic stroke and has a clinically relevant therapeutic window. PMID:10557349

  18. Vasculitic neuropathy following exposure to minocycline

    PubMed Central

    Baratta, John M.; Dyck, P. James B.; Brand, Patricio; Thaisetthawatkul, Pariwat; Dyck, Peter J.; Engelstad, JaNean K.; Goodman, Brent

    2015-01-01

    Objective: To report 3 patients with minocycline-induced autoimmunity resulting in peripheral nerve vasculitis. Methods: We report 3 patients who, during minocycline treatment for acne vulgaris, developed subacute onset of pain and weakness caused by vasculitis in single and multiple mononeuropathy patterns. Results: Each patient underwent either a nerve or muscle biopsy that confirmed vasculitis. One patient additionally developed systemic symptoms (including fever, fatigue, and night sweats) and another had a posterior circulation stroke. Symptoms developed with either early or prolonged use of minocycline. Despite withdrawal of minocycline, patients needed long-term immunotherapy to gain neurologic improvement. Conclusions: Our findings suggest that the typical neuropathy associated with minocycline use is painful single or multiple mononeuropathy due to peripheral nerve vasculitis, which may also be accompanied by presumed CNS vasculitis (presenting as stroke). PMID:26601119

  19. 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. PMID:25487770

  20. Acute Heart Failure Treatment.

    PubMed

    Levy, Phillip D; Bellou, Abdel

    2013-06-01

    Dyspnea is the predominant symptom for patients with acute heart failure and initial treatment is largely directed towards the alleviation of this. Contrary to conventional belief, not all patients present with fluid overload and the approach to management is rapidly evolving from a solitary focus on diuresis to one that more accurately reflects the complex interplay of underlying cardiac dysfunction and acute precipitant. Effective treatment thus requires an understanding of divergent patient profiles and an appreciation of various therapeutic options for targeted patient stabilization. The key principle within this paradigm is directed management that aims to diminish the work of breathing through situation appropriate ventillatory support, volume reduction and hemodynamic improvement. With such an approach, clinicians can more efficiently address respiratory discomfort while reducing the likelihood of avoidable harm. PMID:24223323

  1. 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

  2. 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

  3. Proteomic analysis of the anti-inflammatory action of minocycline

    PubMed Central

    Dunston, Christopher R; Griffiths, Helen R; Lambert, Peter A; Staddon, Susan; Vernallis, Ann B

    2011-01-01

    Minocycline possesses anti-inflammatory properties independently of its antibiotic activity although the underlying molecular mechanisms are unclear. Lipopolysaccharide (LPS)-induced cytokines and pro-inflammatory protein expression are reduced by minocycline in cultured macrophages. Here, we tested a range of clinically important tetracycline compounds (oxytetracycline, doxycycline, minocycline and tigecycline) and showed that they all inhibited LPS-induced nitric oxide production. We made the novel finding that tigecycline inhibited LPS-induced nitric oxide production to a greater extent than the other tetracycline compounds tested. To identify potential targets for minocycline, we assessed alterations in the macrophage proteome induced by LPS in the presence or absence of a minocycline pre-treatment using 2-DE and nanoLC-MS. We found a number of proteins, mainly involved in cellular metabolism (ATP synthase β-subunit and aldose reductase) or stress response (heat shock proteins), which were altered in expression in response to LPS, some of which were restored, at least in part, by minocycline. This is the first study to document proteomic changes induced by minocycline. The observation that minocycline inhibits some, but not all, of the LPS-induced proteomic changes shows that minocycline specifically affects some signalling pathways and does not completely inhibit macrophage activation. PMID:21182193

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

    PubMed

    Hanlon, Lauren A; Huh, Jimmy W; Raghupathi, Ramesh

    2016-03-01

    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

  5. 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

  6. Commonly Used Acute Migraine Treatments

    MedlinePlus

    ... that make headaches worse (or lead to decreased responsiveness to other drug therapies) Patient preference Goals of ... Reduce frequency, severity, and duration of attacks Improve responsiveness to treatment of acute attacks Reduce level of ...

  7. In Vivo and In Vitro Efficacy of Minocycline-Based Combination Therapy for Minocycline-Resistant Acinetobacter baumannii.

    PubMed

    Yang, Ya-Sung; Lee, Yi; Tseng, Kuo-Chuan; Huang, Wei-Cheng; Chuang, Ming-Fen; Kuo, Shu-Chen; Lauderdale, Tsai-Ling Yang; Chen, Te-Li

    2016-07-01

    Minocycline-based combination therapy has been suggested to be a possible choice for the treatment of infections caused by minocycline-susceptible Acinetobacter baumannii, but its use for the treatment of infections caused by minocycline-resistant A. baumannii is not well established. In this study, we compared the efficacy of minocycline-based combination therapy (with colistin, cefoperazone-sulbactam, or meropenem) to that of colistin in combination with meropenem for the treatment of minocycline-resistant A. baumannii infection. From 2006 to 2010, 191 (17.6%) of 1,083 A. baumannii complex isolates not susceptible to minocycline from the Taiwan Surveillance of Antimicrobial Resistance program were collected. Four representative A. baumannii isolates resistant to minocycline, amikacin, ampicillin-sulbactam, ceftazidime, ciprofloxacin, cefepime, gentamicin, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam were selected on the basis of the diversity of their pulsotypes, collection years, health care setting origins, and geographic areas of origination. All four isolates had tetB and overexpressed adeABC, as revealed by quantitative reverse transcription-PCR. Among all minocycline-based regimens, only the combination with colistin produced a fractional inhibitory concentration index comparable to that achieved with meropenem combined with colistin. Minocycline (4 or 16 μg/ml) in combination with colistin (0.5 μg/ml) also synergistically killed minocycline-resistant isolates in time-kill studies. Minocycline (50 mg/kg of body weight) in combination with colistin (10 mg/kg) significantly improved the survival of mice and reduced the number of bacteria present in the lungs of mice compared to the results of monotherapy. However, minocycline (16 μg/ml)-based therapy was not effective at reducing biofilm-associated bacteria at 24 or 48 h when its effectiveness was compared to that of colistin (0.5 μg/ml) and meropenem (8 μg/ml). The clinical use of

  8. Minocycline inhibits the production of the precursor form of nerve growth factor by retinal microglial cells☆

    PubMed Central

    Yang, Xiaochun; Duan, Xuanchu

    2013-01-01

    A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. Minocycline (90 mg/kg) was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells, glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis. PMID:25206672

  9. Singing the "Minocycline Blues".

    PubMed

    Federman, Daniel G; Haas, Andrea V; Chang, John J

    2016-01-01

    A variety of medical conditions and medications can lead to cutaneous dyschromia. We report a case of minocycline dyschromia that had been mistakenly attributed to chronic actinic purpura. PMID:26882786

  10. Acute Migraine Treatment in Adults.

    PubMed

    Becker, Werner J

    2015-06-01

    There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office-based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID-triptan combinations, dihydroergotamine, non-opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti-emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence-based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication

  11. 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

  12. Minocycline-induced orbital rim discoloration.

    PubMed

    Ballard, Tiffany N S; Briceño, César A

    2016-04-01

    A 20-year-old woman underwent lacrimal gland biopsy for unilateral swelling and was unexpectedly found to have olive-green discoloration of her orbital rim. Postoperative questioning revealed that as a teenager she had been treated for acne with minocycline, a semisynthetic tetracycline antibiotic and a first-line treatment for moderate and severe acne. While hyperpigmentation is a known side effect of minocycline, reports of pigmentation changes of the periorbital bones are relatively rare and could pose a diagnostic dilemma during surgery. PMID:26988772

  13. Protocol and Rationale-The Efficacy of Minocycline as an Adjunctive Treatment for Major Depressive Disorder: A Double Blind, Randomised, Placebo Controlled Trial

    PubMed Central

    Maes, Michael; Ashton, Melanie; Berk, Lesley; Kanchanatawan, Buranee; Sughondhabirom, Atapol; Tangwongchai, Sookjareon; Ng, Chee; Dowling, Nathan; Malhi, Gin S.; Berk, MIchael

    2014-01-01

    While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression. PMID:25598820

  14. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePlus

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

  15. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePlus

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

  16. Drug repurposing of minocycline against dengue virus infection.

    PubMed

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

    2016-09-01

    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. PMID:27396621

  17. 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

  18. 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. PMID:20352584

  19. Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients with Persistent Symptoms

    PubMed Central

    Kelly, Deanna L.; Sullivan, Kelli M.; McEvoy, Joseph P; McMahon, Robert P.; Wehring, Heidi J.; Liu, Fang; Warfel, Dale; Vyas, Gopal; Richardson, Charles M.; Fischer, Bernard A.; Keller, William R.; Mathew Koola, Maju; Feldman, Stephanie; Russ, Jessica C.; Keefe, Richard S.; Osing, Jennifer; Hubzin, Leeka; August, Sharon; Walker, Trina M.; Buchanan, Robert W.

    2015-01-01

    Objective Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10 week, double blind placebo-controlled trial. Primary outcomes tested were positive and cognitive symptoms, while avolition, anxiety/depression and negative symptoms were secondary outcomes. Methods Schizophrenia and schizoaffective participants (N=52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily) (N=29) or placebo (N=23). Results Brief Psychiatric Rating Scale (BPRS) psychosis factor (p=0.098, effect size ES=0.39) and BPRS total score (p=0.075, effect size 0.55) were not significant. A ≥30% change in total BPRS symptoms was observed in 7/28 (25%) among minocycline and 1/23 (4%) among placebo participants, respectively (p=0.044). Global cognitive function (MATRICS Consensus Cognitive Battery, MCCB) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (p=0.03), with significant improvement in working memory favoring minocycline (p=0.023, ES 0.41). The SANS total score did not differ, but significant improvement in avolition with minocycline was noted (p=0.012, ES=0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (p=0.028, ES=0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared to placebo. Conclusion Minocycline’s effect on the MCCB composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings. PMID:26082974

  20. Acute treatment of atrial fibrillation.

    PubMed

    Kowey, P R; Marinchak, R A; Rials, S J; Filart, R A

    1998-03-12

    Atrial fibrillation (AFib) is a common clinical entity, responsible for significant morbidity and mortality, but it also accounts for a large percentage of healthcare dollar expenditures. Efforts to treat this arrhythmia in the past have focused on subacute antithrombotic therapy and eventually use of antiarrhythmic drugs for maintenance of sinus rhythm. However, there has been a growing interest in the concept of acute electrical and pharmacologic conversion. This treatment strategy has a number of benefits, including immediate alleviation of patient symptoms, avoidance of antithrombotic therapy, and prevention of electrophysiologic remodeling, which is thought to contribute to the perpetuation of the arrhythmia. There is also increasing evidence that this is a cost-effective strategy in that it may obviate admission to the hospital and the cost of long-term therapy. This article represents a summary of the treatments that may be used acutely to control the ventricular response to AFib, prevent thromboembolic events, and provide for acute conversion either pharmacologically or electrically. It includes information on modalities that are currently available and those that are under active development. We anticipate that an active, acute treatment approach to AFib and atrial flutter will become the therapeutic norm in the next few years, especially as the benefits of these interventions are demonstrated in clinical trials. PMID:9525568

  1. Comparative Neuroprotective Effects of Dexamethasone and Minocycline during Hepatic Encephalopathy

    PubMed Central

    Gamal, Maha; Abdel Wahab, Zainab; Eshra, Mohamed; Rashed, Laila; Sharawy, Nivin

    2014-01-01

    Objective. Encephalopathy and brain edema are serious complications of acute liver injury and may lead to rapid death of patients. The present study was designed to investigate the role of the inflammatory mediators and oxidative stress in the cytotoxic brain oedema and the neuroprotective effects of both minocycline and dexamethasone. Methods. 48 male albino rats were divided into 4 groups: control group, acute liver injury (ALI) group, minocycline pretreated ALI group, and dexamethasone pretreated ALI group. 24 hours after acute liver injury serum ammonia, liver enzymes, brain levels of heme oxygenase-1 gene, iNOS gene expression, nitrite/nitrate, and cytokines were measured. In addition, the grades of encephalopathy and brain water content were assessed. Results. ALI was associated with significant increases in all measured inflammatory mediators, oxidative stress, iNOS gene expression, and nitrite/nitrate. Both minocycline and dexamethasone significantly modulated the inflammatory changes and the oxidative/nitrosative stress associated with ALI. However, only minocycline but not dexamethasone significantly reduced the cytotoxic brain oedema. Conclusion. Both minocycline and dexamethasone could modulate inflammatory and oxidative changes observed in brain after ALI and could be novel preventative therapy for hepatic encephalopathy episodes. PMID:24693424

  2. Field trial on efficacy of supervised monthly dose of 600 mg rifampin, 400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first results.

    PubMed

    Mane, I; Cartel, J L; Grosset, J H

    1997-06-01

    In 1995, a field trial was implemented in Senegal in order to evaluate the efficacy of a regimen based on the monthly supervised intake of rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg to treat leprosy. During the first year of the trial, 220 patients with active leprosy (newly detected or relapsing after dapsone monotherapy) were recruited: 102 paucibacillary (PB) (60 males and 42 females) and 118 multibacillary (MB) (71 males and 47 females). All of them accepted the new treatment (none requested to be preferably put under standard WHO/MDT), no clinical sign which could be considered as a toxic effect of the drug was noted, and none of the patients refused to continue treatment because of any clinical trouble. The compliance was excellent: the 113 patients (PB and MB) detected during the first 6 months of the trial have taken six monthly doses in 6 months, as planned. The rate of clearance and the progressive decrease of cutaneous lesions was satisfactory. Although it is too soon to give comprehensive results, it should be noted that no treatment failure was observed in the 56 PB patients who have completed treatment and have been followed up for 6 months. The long-term efficacy of the new regimen is to be evaluated on the rate of relapse during the years following the cessation of treatment. If that relapse rate is acceptable (similar to that observed in patients after treatment with current standard WHO/ MDT), the new regimen could be a solution to treat, for instance, patients very irregular and/or living in remote or inaccessible areas since no selection of rifampin-resistant Mycobacterium leprae should be possible (a monthly dose of ofloxacin and minocycline being as effective as a dose of dapsone and clofazimine taken daily for 1 month). Nevertheless, until longer term results of this and other trials become available, there is no justification for any change in the treatment strategy, and all leprosy patients should be put under standard WHO

  3. Minocycline-induced hyperpigmentation

    PubMed Central

    Fiscus, Valena; Hankinson, Andrew; Alweis, Richard

    2014-01-01

    A 62-year-old male with a long history of rosacea, which was well controlled on minocycline, presented to his primary care physician for routine examination. Physical examination was noted for non-palpable, non-pruritic blue patches of hyperpigmentation on the medial aspects of his lower extremities bilaterally. Recognition and management of the findings are discussed. PMID:25147636

  4. Photo-onycholysis from minocycline. Side effects of minocycline therapy

    SciTech Connect

    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.

  5. 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

  6. Combined minocycline plus pyruvate treatment enhances effects of each agent to inhibit inflammation, oxidative damage, and neuronal loss in an excitotoxic animal model of Huntington's disease.

    PubMed

    Ryu, J K; Choi, H B; McLarnon, J G

    2006-09-15

    The combination effects of minocycline (MC), a second-generation tetracycline compound and pyruvate (PY), a glycolysis end metabolite with antioxidant activity were investigated in the rat striatum following an excitotoxic insult. Striatal injection of quinolinic acid (QUIN) resulted in marked inflammation characterized by microgliosis, astrogliosis and enhanced expressions of pro-inflammatory enzymes inducible nitric oxide synthase and cyclooxygenase-2. Inflammatory responses were attenuated with administration of either MC or PY, however, the combination of both compounds was significantly more effective in reducing inflammation relative to MC or PY applied alone. Immunohistochemical analysis at 7 days post-intrastriatal QUIN injection showed extensive oxidative stress evident as lipid peroxidation, oxidative DNA damage and reactive oxygen species formation which was partially decreased by each agent applied separately but markedly inhibited with the combination of the two compounds. In addition, combination treatments significantly reduced neuronal loss in QUIN-injected striatum compared with the agents applied separately. Furthermore, long-term combination treatment decreased striatal lesions and inflammation after QUIN injection. These results demonstrate that MC and PY confer a considerably enhanced anti-inflammatory and neuroprotective efficacy when applied together and suggest this combinatorial procedure as a novel therapeutic strategy in neurodegenerative disorders such as Huntington's disease which exhibit excitotoxic insults. PMID:16809003

  7. Sequential Therapy with Minocycline and Candesartan Improves Long Term Recovery after Experimental Stroke

    PubMed Central

    Soliman, Sahar; Ishrat, Tauheed; Fouda, Abdelrahman Y.; Patel, Ami; Pillai, Bindu; Fagan, Susan C.

    2015-01-01

    Background Minocycline and candesartan have both shown promise as candidate therapeutics in ischemic stroke, with multiple, and somewhat contrasting, molecular mechanisms. Minocycline is an anti-inflammatory, antioxidant and anti-apoptotic agent and a known inhibitor of matrix metalloproteinases (MMPs). Yet, minocycline exerts antiangiogenic effects both in vivo and in vitro. Candesartan promotes angiogenesis and activates MMPs. Aligning these therapies with the dynamic processes of injury and repair after ischemia is likely to improve success of treatment. Objective In this study, we hypothesize that opposing actions of minocycline and candesartan on angiogenesis, when administered simultaneously, will reduce the benefit of candesartan treatment. Therefore, we propose a sequential combination treatment regimen to yield a better outcome and preserve the proangiogenic potential of candesartan. Methods In vitro angiogenesis was assessed using human brain endothelial cells. In vivo, Wistar rats subjected to 90-minute middle cerebral artery occlusion (MCAO) were randomized into 4 groups: saline, candesartan, minocycline and sequential combination of minocycline and candesartan. Neurobehavioral tests were performed 1, 3, 7 and 14 days after stroke. Brain tissue was collected on day 14 for assessment of infarct size and vascular density. Results Minocycline, when added simultaneously, decreased the proangiogenic effect of candesartan treatment in vitro. Sequential treatment, however, preserved the proangiogenic potential of candesartan both in vivo and in vitro, improved neurobehavioral outcome and reduced infarct size. Conclusion Sequential combination therapy with minocycline and candesartan improves long term recovery and maintains candesartan’s proangiogenic potential. PMID:26004281

  8. [Surgical treatment of acute mediastinitis].

    PubMed

    Krüger, M; Decker, S; Schneider, J P; Haverich, A; Schega, O

    2016-06-01

    Despite modern intensive care management, acute mediastinitis is still associated with a high morbidity and mortality (up to approximately 40 %). Effective antibiotic therapy, intensive care management, elimination of the causative sources of infection and drainage of the affected mediastinal compartments are the cornerstones of therapy in a multidisciplinary treatment concept. Early diagnosis, prompt and uncompromising initial therapy and planned computed tomography (CT) control after the first stages of therapy in order to decide on the necessity for surgical re-interventions are essential for achieving optimal results. Knowledge of the specific anatomical characteristics is crucial for the understanding of this disease and its treatment; therefore, the current knowledge on fascial layers and interstitial spaces from the neck to the mediastinum is described and discussed. A possible foudroyant spread of the infection, especially within the posterior mediastinum, has to be anticipated. The approach to the mediastinum depends on the mediastinal compartments affected, on the causative disease and on the patient's clinical situation. The surgical approach should be adapted to the particular clinical situation of the individual patient and to the surgical experience of the surgeon. When in doubt, the more invasive approach to the mediastinum, such as bilateral thoracotomy, is recommended. An ascending mediastinitis due to pancreatitis is a very rare condition; however, as chest pains are often the main clinical sign surgeons should be aware of this differential diagnosis. An intraoperative brown-black serous fluid in the mediastinal tissue is virtually pathognomonic. The treatment results of esophageal perforation as the most frequent cause of mediastinitis have been improved by integration of various interventional procedures. Hyperbaric oxygen therapy or immunoglobulin treatment can play an auxiliary role in selected patients with acute mediastinitis. PMID

  9. Testicular Pain Associated With Minocycline Use

    PubMed Central

    Kucherov, Victor; Hulbert, William; Wu, Guan

    2015-01-01

    Two males ages 16 and 23 years presented with new testicular pain while taking minocycline. Both patients experienced resolution of their symptoms only after minocycline discontinuation. Testicular pain with minocycline use has been previously described, however only in the setting of systemic autoimmune reactions (which were absent here). These cases represent probable rare adverse reactions to minocycline. For patients taking minocycline who experience otherwise unexplained testicular pain, a trial discontinuation of this medication should be considered. PMID:26793506

  10. 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

  11. A Pilot Clinical Trial of Creatine and Minocycline in Early Parkinson Disease: 18-Month Results

    PubMed Central

    2015-01-01

    Objective To report an 18-month follow-up on creatine and minocycline futility study, the Neuroprotective Exploratory Trials in Parkinson Disease, Futility Study 1 (NET-PD FS-1). Background The NET-PD FS-1 futility study on creatine and minocycline found neither agent futile in slowing down the progression of disability in Parkinson disease (PD) at 12 months using the prespecified futility threshold. An additional 6 months of follow-up aimed to assess safety and potential interactions of the study interventions with anti-parkinsonian therapy. Methods Additional 6 months of follow-up in randomized, blinded phase II trial of creatine (dosage, 10 g/d) and minocycline (dosage, 200 mg/d) in subjects with early PD. Results By 18 months, symptomatic treatment of PD symptoms was required in 61% of creatine, 62% of minocycline, and 60% of placebo-treated subjects. Study treatment was prematurely discontinued in 9%, 23%, and 6% of subjects in the creatine, minocycline, and placebo arms, respectively. Creatine and minocycline did not seem to adversely influence the response to symptomatic therapy nor increase adverse events. Conclusions Data from this small, 18-month phase II trial of creatine and minocycline do not demonstrate safety concerns that would preclude a large, phase III efficacy trial, although the decreased tolerability of minocycline is a concern. PMID:18520981

  12. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia.

    PubMed

    Tikka, T; Fiebich, B L; Goldsteins, G; Keinanen, R; Koistinaho, J

    2001-04-15

    Minocycline, a semisynthetic tetracycline derivative, protects brain against global and focal ischemia in rodents. We examined whether minocycline reduces excitotoxicity in primary neuronal cultures. Minocycline (0.02 microm) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 microm glutamate or 100 microm kainate for 24 hr. Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1beta (IL-1beta) and was followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures. Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1beta. Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1beta also in pure microglia cultures, and these responses were inhibited by minocycline. In both SC and pure microglia cultures, excitotoxins activated p38 mitogen-activated protein kinase (p38 MAPK) exclusively in microglia. Minocycline inhibited p38 MAPK activation in SC cultures, and treatment with SB203580, a p38 MAPK inhibitor, but not with PD98059, a p44/42 MAPK inhibitor, increased neuronal survival. In pure microglia cultures, glutamate induced transient activation of p38 MAPK, and this was inhibited by minocycline. These findings indicate that the proliferation and activation of microglia contributes to excitotoxicity, which is inhibited by minocycline, an antibiotic used in severe human infections. PMID:11306611

  13. Minocycline Attenuates Kidney Injury in a Rat Model of Streptozotocin-Induced Diabetic Nephropathy.

    PubMed

    Yuan, Hongping; Zhang, Xiaoxuan; Zheng, Wei; Zhou, Hui; Zhang, Bo-Yin; Zhao, Dongxu

    2016-01-01

    The effects of minocycline on the development of diabetic nephropathy (DN) in streptozotocin (STZ) induced diabetic rats were evaluated in this study. The diabetes rats with DN were induced by STZ (55 mg/kg) injection. The experiment included 5 groups 1) normal, 2) normal plus minocycline for 16 weeks, 3) DN plus vehicle, 4) DN plus minocycline 16 weeks and 5) DN plus minocycline for 8 weeks. The pathological changes were analyzed by hematoxylin and eosin (H&E) staining and the apoptotic cells were stained by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. The mRNA expression of caspase-3, Bax and Bcl-2 in the kidney tissues was detected by quantitative RT-PCR. The biochemical parameters of blood and urine were determined by biochemical analyzer. Treatment with minocycline reduced the urine volume, 24-h urine protein, serum creatinine (Scr), blood urea nitrogen (BUN) but not blood alanine aminotransferase (ALT) in the DN rats. Furthermore, treatment with minocycline improved the pathological score of STZ-injured kidney and reduced the numbers of apoptotic cells in the kidney of DN rats. Moreover, minocycline mitigated the expression of caspase-3 and Bax mRNA, but increased Bcl-2 expression in the kidney of DN rats. These data indicated that minocycline improved the STZ-induced kidney damages, at least partially by protection form long-term hyperglycemia-induced kidney cell apoptosis. PMID:27476934

  14. [Improvement of treatment results of acute cholecystitis].

    PubMed

    Sovtsov, S A; Prilepina, E V

    2015-01-01

    The aim of this study was investigation of treatment results of acute cholecystitis according to suggested forms of cholecystitis by international experts in the research (Tokyo-2007). It was analyzed the immediate treatment results of 1399 patients with acute cholecystitis for the last 4 years in the Chelyabinsk Regional Hospital No3. 912 patients had acute cholecystitis I degree (easy cholecystitis), 270 patients--II (moderate) degree and 217 patients--III degree (severe cholecystitis). It was operated 1281 patients. Operating activity was 91.5%. Postoperative mortality in whole patients group was 0.78%. The authors suggested the main principles such as early, differentiated by the volume operative interventions according to graduations of investigation "Tokyo-2007". Controlled trial of treatment results of patients randomized on three degrees of acute cholecystitis observed appropriateness of allocation of these groups. It is necessary for differentiated treatment and improvement of treatment results of patients with acute cholecystitis. PMID:26031820

  15. Matrix Metalloproteinases and Minocycline: Therapeutic Avenues for Fragile X Syndrome

    PubMed Central

    Siller, Saul S.; Broadie, Kendal

    2012-01-01

    Fragile X syndrome (FXS) is the most common known genetic form of intellectual disability and autism spectrum disorders. FXS patients suffer a broad range of other neurological symptoms, including hyperactivity, disrupted circadian activity cycles, obsessive-compulsive behavior, and childhood seizures. The high incidence and devastating effects of this disease state make finding effective pharmacological treatments imperative. Recently, reports in both mouse and Drosophila FXS disease models have indicated that the tetracycline derivative minocycline may hold great therapeutic promise for FXS patients. Both models strongly suggest that minocycline acts on the FXS disease state via inhibition of matrix metalloproteinases (MMPs), a class of zinc-dependent extracellular proteases important in tissue remodeling and cell-cell signaling. Recent FXS clinical trials indicate that minocycline may be effective in treating human patients. In this paper, we summarize the recent studies in Drosophila and mouse FXS disease models and human FXS patients, which indicate that minocycline may be an effective FXS therapeutic treatment, and discuss the data forming the basis for the proposed minocycline mechanism of action as an MMP inhibitor. PMID:22685676

  16. [Thrombolytic treatment of acute stroke].

    PubMed

    Amiri, H; Hacke, W; Bösel, J

    2011-11-01

    Ischemic stroke is a medical emergency and must be treated as quickly as possible according to the "time-is-brain" concept. At present, intravenous administration of recombinant tissue plasminogen activator (rt-PA) within the first 4.5 h from stroke onset is the only effective treatment but is currently still only approved within the first 3 h from onset of symptoms (0.9 mg/kg body weight, maximum dose 90 mg, 10% of the cumulative dose as bolus, remaining 90% subsequently infused within 60 min). The therapeutic effect of magnetic resonance imaging (MRI) based thrombolytic therapy beyond the 4.5 h time window remains to be proven. Proximal occlusions of the middle cerebral artery can be treated successfully within the first 6 h from stroke onset by catheter-based intra-arterial administration of plasminogen activator leading to a significant improvement of outcome. Acute basilar artery occlusion should be treated in specialized centres using intra-arterial application of urokinase, rt-PA or mechanical recanalization but intravenous thrombolysis beyond the 3 h window is an acceptable alternative. PMID:21922224

  17. 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.

  18. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  19. Treatment Options for Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  20. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  1. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  2. Open Treatment of Acute Scapholunate Instability.

    PubMed

    Swanstrom, Morgan M; Lee, Steve K

    2015-08-01

    Acute treatment of scapholunate instability is important to prevent future complications of dorsal intercalated segment instability and scapholunate advanced collapse. An understanding of the fundamental normal and abnormal mechanics of this problem is vital. Diagnosis in the acute phase is based on clinical and radiographic findings and treatment focuses on primary scapholunate interosseous ligament repair with a reinforcing dorsal capsulodesis. Suture anchor repair with a modified "double-dorsal" capsulodesis is described. Current data show that open repair is a viable option in the acute setting with most patients demonstrating good to excellent functional, clinical, and radiographic results. PMID:26205704

  3. Minocycline induces protective autophagy in vascular endothelial cells exposed to an in vitro model of ischemia/reperfusion-induced injury

    PubMed Central

    DONG, WENBIN; XIAO, SHIGENG; CHENG, MIN; YE, XIAODI; ZHENG, GAOLI

    2016-01-01

    Minocycline has been reported to exhibit advantageous effects on ischemic stroke; however, the precise mechanism of minocycline remains to be established. In the present study, human umbilical vein endothelial cells (HUVECs) were subjected to in vitro simulated ischemia/reperfusion conditions to determine the potential effect of minocycline-induced autophagy on HUVEC damage under oxygen-glucose deprivation/reperfusion (OGD/R). The study demonstrated that minocycline enhanced autophagy in a dose-dependent manner in HUVECs exposed to OGD/R, and only low-dose minocycline protected HUVECs from OGD/R-induced damage. Subsequently, 3-methyladenine (3-MA) was added into the culture media and the protective effect of minocycline was abolished. At the same time, it has been observed that simultaneous treatment with 3-MA also inhibited the autophagy activity induced by minocycline. This finding could suggest that autophagy induced by minocycline serves as one of the potential protective mechanism underlying the beneficial effects of minocycline on ischemic injury. PMID:26893833

  4. 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. PMID:26143258

  5. Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures.

    PubMed

    Corbacella, Elisa; Lanzoni, Irene; Ding, Dalian; Previati, Maurizio; Salvi, Richard

    2004-11-01

    Minocycline, a second-generation tetracycline antibiotic used against gram-negative and gram-positive bacteria, protects against a wide range of neurodegenerative disorders by inhibiting caspases, iNOS and the release of cytochrome c. Since aminoglycoside antibiotics damage sensory hair cells in the inner ear by activating caspase-mediated cell death pathways, we hypothesized that minocycline would protect against gentamicin (GM) ototoxicity. To test this hypothesis, postnatal day 3 (P3) rat, cochlear organotypic cultures were treated with GM alone or in combination with minocycline (10-500 microM). Treatment with GM induced a dose-dependent loss of outer hair cells (OHC) and inner hair cells (IHC). Addition of minocycline to the GM-treated cultures greatly reduced the amount of GM-induced hair cell damage in P3 cochlear cultures. The greatest protection was achieved with 100 microM of minocycline. Application of minocycline alone had no adverse effects on hair cell survival. The advantage of this combination therapy is that minocycline prevents GM-induced hair cell loss while helping to suppress the bacterial infection. PMID:15504599

  6. Treatment of acute lower limb ischaemia.

    PubMed

    Lukasiewicz, Aleksander

    2016-05-01

    Acute lower limb ischaemia poses a major threat to limb survival. For many years surgical thromboembolectomy was the mainstay of treatment. Recent years have brought an endovascular revolution in the management of acute lower limb ischaemia. A wide range of endovascular procedures can nowadays be employed, providing results at least as good as the traditional surgical approach. This paper is an overview of currently utilised endovascular options as well as recent modifications of standard surgical techniques. PMID:27129066

  7. Evolving Treatments for Acute Ischemic Stroke.

    PubMed

    Zerna, Charlotte; Hegedus, Janka; Hill, Michael D

    2016-04-29

    The purpose of this article is to review advances in stroke treatment in the hyperacute period. With recent evolutions of technology in the fields of imaging, thrombectomy devices, and emergency room workflow management, as well as improvement in statistical methods and study design, there have been ground breaking changes in the treatment of acute ischemic stroke. We describe how stroke presents as a clinical syndrome and how imaging as the most important biomarker will help differentiate between stroke subtypes and treatment eligibility. The evolution of hyperacute treatment has led to the current standard of care: intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation. All patients with acute ischemic stroke are in need of hyperacute secondary prevention because the risk of recurrence is highest closest to the index event. The dominant themes of modern stroke care are the use of neurovascular imaging and speed of diagnosis and treatment. PMID:27126651

  8. Minocycline fails to protect cerebellar granular cell cultures against malonate-induced cell death.

    PubMed

    Fernandez-Gomez, F J; Gomez-Lazaro, M; Pastor, D; Calvo, S; Aguirre, N; Galindo, M F; Jordán, J

    2005-11-01

    Experimental and clinical studies support the view that the semisynthetic tetracycline minocycline exhibits neuroprotective roles in several models of neurodegenerative diseases, including ischemia, Huntington, Parkinson diseases, and amyotrophic lateral sclerosis. However, recent evidence indicates that minocycline does not always present beneficial actions. For instance, in an in vivo model of Huntington's disease, it fails to afford protection after malonate intrastriatal injection. Moreover, it reverses the neuroprotective effect of creatine in nigrostriatal dopaminergic neurons. This apparent contradiction prompted us to analyze the effect of this antibiotic on malonate-induced cell death. We show that, in rat cerebellar granular cells, the succinate dehydrogenase inhibitor malonate induces cell death in a concentration-dependent manner. By using DFCA, monochlorobimane and 10-N-nonyl-Acridin Orange to measure, respectively, H2O2-derived oxidant species and reduced forms of GSH and cardiolipin, we observed that malonate induced reactive oxygen species (ROS) production to an extent that surpasses the antioxidant defense capacity of the cells, resulting in GSH depletion and cardiolipin oxidation. The pre-treatment for 4 h with minocycline (10-100 microM) did not present cytoprotective actions. Moreover, minocycline failed to block ROS production and to abrogate malonate-induced oxidation of GSH and cardiolipin. Additional experiments revealed that minocycline was also unsuccessful to prevent the mitochondrial swelling induced by malonate. Furthermore, malonate did not induce the expression of the iNOS, caspase-3, -8, and -9 genes which have been shown to be up-regulated in several models where minocycline resulted cytoprotective. In addition, malonate-induced down-regulation of the antiapoptotic gene Bcl-2 was not prevented by minocycline, controversially the mechanism previously proposed to explain minocycline protective action. These results suggest that the

  9. 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. PMID:26681545

  10. Minocycline enhances hippocampal memory, neuroplasticity and synapse-associated proteins in aged C57 BL/6 mice.

    PubMed

    Jiang, Ying; Liu, Yingying; Zhu, Cansheng; Ma, Xiaomeng; Ma, Lili; Zhou, Linli; Huang, Qiling; Cen, Lei; Pi, Rongbiao; Chen, Xiaohong

    2015-05-01

    Previous studies have suggested that minocycline can attenuate cognitive deficits in animal models of conditions such as Alzheimer's disease and cerebral ischemia through inhibiting microglia associated anti-inflammatory actions. However the pathway that minocycline targets to enhance cognitive performance is not fully defined. Here we examined the effects of minocycline on learning and memory in aged (22-month-old) C57 BL/6 mice. We treated one group of mice with minocycline (30 mg/kg/day), and another group of mice with donepezil (2 mg/kg/day) as a positive control. The Morris water maze and passive avoidance tests were used to evaluate the effects of minocycline on learning and memory deficits. We also used high-frequency stimulation-induced long-term potentiation and Golgi-Cox staining to assess the effect of minocycline on synaptic plasticity and synaptogenesis. The effects of minocycline on synapse-associated signaling proteins were determined by western blot. We found that minocycline ameliorates cognitive deficits, enhances neuroplasticity, activates brain-derived neurotrophic factor- extracellular signal-regulated kinases signaling and increases expression of Arc, EGR1 and PSD-95 in the CA1 and dentate gyrus regions of the hippocampus in aged mice. The effects of minocycline in aged mice were similar to those of donepezil. Our results suggest that minocycline could improve learning and memory through enhancing synaptic plasticity and synaptogenesis, modulating the expression of synapse-associated signaling proteins, which provide a rationale for exploring the viability of using minocycline treatment in cognitive deficits. PMID:25838119

  11. Minocycline mechanism of neuroprotection involves the Bcl-2 gene family in optic nerve transection.

    PubMed

    Levkovitch-Verbin, Hani; Waserzoog, Yael; Vander, Shelly; Makarovsky, Daria; Ilia, Piven

    2014-10-01

    The second-generation tetracycline, minocycline, has been shown to exhibit neuroprotective therapeutic benefits in many neurodegenerative diseases including experimental glaucoma and optic nerve transection (ONT). This study investigated the mechanism underlying minocycline neuroprotection in a model of ONT. ONT was applied unilaterally in 36 Wistar rat eyes. The rats were randomly divided into a minocycline (22 mg/kg/d) treatment group and a saline treatment group (control). Treatment (minocycline or saline) was given by intraperitoneal injections initiated 3 d before ONT and continued daily until the end of the experiment. The involvement of pro-apoptotic, pro-survival and inflammatory pathways was analyzed by quantitative Real-Time Polymerase Chain Reaction at 4 h and 3 d after the transection in both treatment groups. The involvement of Bcl-2 protein was evaluated by immunohistochemistry. We found that Minocycline significantly increased the expression of the antiapoptotic gene bcl-2 4 h after transection (n = 8, p = 0.008) and decreased the expression of Bax at the same time point (n = 8, p = 0.03). Tumor Necrosis Factor α (TNFα), Inhibitor of Apoptosis Protein (IAP1) and Gadd45α were significantly upregulated in the retinas of eyes with ONTs compared to control (n = 10 for each gene, p = 0.02, p = 0.03, p = 0.04, respectively) but this effect was unaffected by minocycline. This study further support that the mechanism underlying minocycline neuroprotection involves the Bcl-2 gene family, suggesting that minocycline has antiapoptotic properties that support its value as a promising neuroprotective drug. PMID:24410139

  12. [SURGICAL TREATMENT OF AN ACUTE MESENTERIAL ISCHEMIA].

    PubMed

    Shepehtko, E N; Garmash, D A; Kurbanov, A K; Marchenko, V O; Kozak, Yu S

    2016-04-01

    Experience of surgical treatment of 143 patients, suffering an acute mesenterial ischemia, was summarized. Isolated intestinal resection was performed in 41 patients (lethality 65.9%), intestinal resection with the mesenterial vessels thrombembolectomy--in 9 (lethality 33.3%). After performance of the combined intervention postoperative lethality was in two times lower, than after isolated intestinal resection. PMID:27434952

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

    PubMed

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

    2013-03-15

    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

  14. Minocycline-induced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects.

    PubMed

    Nisar, Mahrukh S; Iyer, Karthik; Brodell, Robert T; Lloyd, Jenifer R; Shin, Thuzar M; Ahmad, Asad

    2013-01-01

    Minocycline is a tetracycline derivative antibiotic commonly prescribed for acne, rosacea, and other inflammatory skin disorders. Minocycline turns black when oxidized, leading to discoloration of the skin, nails, bulbar conjunctiva, oral mucosa, teeth, bones, and thyroid gland. Hyperpigmentation has been reported after long-term minocycline therapy with at least 100 mg/day. Three types of minocycline-induced cutaneous hyperpigmentation can result. Type I is the most common, and is associated with blue-black discoloration in areas of previous inflammation and scarring. Type II most commonly affects the legs and is characterized by blue-gray pigmentation of previously normal skin. Type III is the least common and is characterized by diffuse muddy-brown discoloration predominantly on sun exposed skin. Minocycline-induced hyperpigmentation may be cosmetically disfiguring and prompt identification is essential. Without treatment, symptoms may take several months, to years to resolve, after discontinuation of the drug. However, the pigmentation may never completely disappear. In fact, there have been few reports of complete resolution associated with any therapeutic intervention. We report a case of a patient on long-term minocycline therapy utilized as an anti-inflammatory agent to control symptoms of rheumatoid arthritis, which led to minocycline-induced hyperpigmentation of the face. To remove the blue-gray cutaneous deposits, 3 Q-switched lasers (Neodymium: yttrium aluminum garnet (Nd:YAG) 1064 nm, Alexandrite 755 nm, and Ruby 694 nm) were used in test areas. The Alexandrite 755 nm laser proved to provide effective clearing of the minocycline hyperpigmentation requiring just 2 treatments, with minimal treatment discomfort and down time. PMID:23754872

  15. Radioimmunotherapy for Treatment of Acute Leukemia.

    PubMed

    Bodet-Milin, Caroline; Kraeber-Bodéré, Françoise; Eugène, Thomas; Guérard, François; Gaschet, Joëlle; Bailly, Clément; Mougin, Marie; Bourgeois, Mickaël; Faivre-Chauvet, Alain; Chérel, Michel; Chevallier, Patrice

    2016-03-01

    Acute leukemias are characterized by accumulation of immature cells (blasts) and reduced production of healthy hematopoietic elements. According to the lineage origin, two major leukemias can be distinguished: acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Although the survival rate for pediatric ALL is close to 90%, half of the young adults with AML or ALL and approximately 90% of older patients with AML or ALL still die of their disease, raising the need for innovative therapeutic approaches. As almost all leukemic blasts express specific surface antigens, targeted immunotherapy appears to be particularly promising. However, published results of immunotherapy alone are generally modest. Radioimmunotherapy (RIT) brings additional therapeutic mechanisms using radiolabeled monoclonal antibodies (mAbs) directed to tumor antigens, thus adding radiobiological cytotoxicity to immunologic cytotoxicity. Because of the high radiosensitivity of tumor cells and the diffuse widespread nature of the disease, making it rapidly accessible to circulating radiolabeled mAbs, acute leukemias represent relevant indications for RIT. With the development of recombinant and humanized mAbs, innovative radionuclides, and more efficient radiolabeling and pretargeting techniques, RIT has significantly improved over the last 10 years. Different approaches of α and β RIT targeting CD22, CD33, CD45, or CD66 antigens have already been evaluated or are currently being developed in the treatment of acute leukemia. This review summarizes the preclinical and clinical studies demonstrating the potential of RIT in treatment of AML and ALL. PMID:26897718

  16. Corticosteroids in the treatment of acute asthma

    PubMed Central

    Alangari, Abdullah A.

    2014-01-01

    Asthma is a prevalent chronic disease of the respiratory system and acute asthma exacerbations are among the most common causes of presentation to the emergency department (ED) and admission to hospital particularly in children. Bronchial airways inflammation is the most prominent pathological feature of asthma. Inhaled corticosteroids (ICS), through their anti-inflammatory effects have been the mainstay of treatment of asthma for many years. Systemic and ICS are also used in the treatment of acute asthma exacerbations. Several international asthma management guidelines recommend the use of systemic corticosteroids in the management of moderate to severe acute asthma early upon presentation to the ED. On the other hand, ICS use in the management acute asthma has been studied in different contexts with encouraging results in some and negative in others. This review sheds some light on the role of systemic and ICS in the management of acute asthma and discusses the current evidence behind their different ways of application particularly in relation to new developments in the field. PMID:25276236

  17. Involvement of pro- and antinociceptive factors in minocycline analgesia in rat neuropathic pain model.

    PubMed

    Rojewska, Ewelina; Popiolek-Barczyk, Katarzyna; Jurga, Agnieszka M; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2014-12-15

    In neuropathic pain the repeated minocycline treatment inhibited the mRNA and protein expression of the microglial markers and metalloproteinase-9 (MMP-9). The minocycline diminished the pronociceptive (IL-6, IL-18), but not antinociceptive (IL-1alpha, IL-4, IL-10) cytokines at the spinal cord level. In vitro primary cell culture studies have shown that MMP-9, TIMP-1, IL-1beta, IL-1alpha, IL-6, IL-10, and IL-18 are of microglial origin. Minocycline reduces the production of pronociceptive factors, resulting in a more potent antinociceptive effect. This change in the ratio between pro- and antinociceptive factors, in favour of the latter may be the mechanism of minocycline analgesia in neuropathy. PMID:25304927

  18. Concurrence of Stevens-Johnson Syndrome and Bilateral Parotitis after Minocycline Therapy

    PubMed Central

    Yoon, Jimi; Lee, Seung Hun; Kim, Tae-Heung; Choi, Deok-Jin; Kim, Jin-Pyeong; Yoon, Tae-Jin

    2010-01-01

    Minocycline is an antibiotic of tetracycline derivatives that is commonly used in the treatment of moderate to severe acne vulgaris. It has been reported to cause rare adverse events from mild cutaneous eruption to severe forms including drug-induced lupus, serum sickness-like reaction, and hypersensitivity reactions, etc. The risks of adverse events attributed to minocycline have not been ascertained reliably and there are concerns about the safety of minocycline which could possibly result in life-threatening events such as the Stevens-Johnson syndrome. Here we demonstrate an unusual case of Stevens-Johnson syndrome in conjunction with bilateral parotitis after the intake of minocycline in a Korean boy suggesting discreet use of the drug. PMID:21103193

  19. A case of minocycline-induced black thyroid associated with papillary carcinoma.

    PubMed

    Nishimoto, Kohei; Kumai, Yoshihiko; Murakami, Daizo; Yumoto, Eiji

    2016-03-01

    We report a rare case of black thyroid accompanied by papillary carcinoma in a patient with an extended history of minocycline treatment. A 78-year-old man was referred to our outpatient clinic with swelling in his neck. He had been taking minocycline for the previous 2 years and 7 months to treat chronic perianal pyoderma. Neck ultrasonography and computed tomography demonstrated a 3.5 × 3.7 × 5.0-cm nodule in the left thyroid lobe, and fine-needle aspiration cytology identified it as a papillary carcinoma. The patient underwent a total thyroidectomy and neck dissection. During the procedure, a distinct black discoloration of the thyroid parenchyma was observed. Histopathology confirmed both the black thyroid and the papillary carcinoma. Based on the thyroid gland's discoloration and the history of minocycline use, the patient was diagnosed with minocycline-induced black thyroid. He was symptom-free 20 months after surgery. PMID:26991226

  20. Neuroprotective effect of minocycline in a rat model of branch retinal vein occlusion.

    PubMed

    Sun, Chuan; Li, Xiao-Xin; He, Xiang-Jun; Zhang, Qi; Tao, Yong

    2013-08-01

    Branch retinal vein occlusion (BRVO) is the second most frequent retinal vascular disorder. Currently the first-line therapies for BRVO include anti-VEGF and dexamethasone implant treatment, however, with direct or indirect damage on retinal neurons, it has limited effect in improving patients visual acuity. Therefore, novel treatments with neuroprotective effect for BRVO retina were expected. Minocycline is a semisynthetic, broad spectrum tetracycline antibiotic with high penetration through the blood brain barrier. The neuroprotective effects of minocycline have been shown in various central nervous system (CNS) disease. Since both CNS and retina were composed of neurons and glials, it is reasonable to expect a neuroprotective effect by minocycline for BRVO retina. Therefore, the aim of the present study was to study whether minocycline has neuroprotective effect in branch retinal vein occlusion (BRVO) and the possible underlying molecular basis. We created BRVO in rats using laser photocoagulation. The animals were then randomly divided into 4 groups to evaluate the effect of minocycline: group A: minocycline 45 mg/kg intraperitoneal injection (i.p.), group B: minocycline 90 mg/kg i.p., group C: normal saline i.p., group D: sham injection. Fundus photography and fluorescein angiography (FA) were conducted. The changes in thickness of retinal layers were measured with optical coherence tomography (OCT) in vivo. We found that retinal edema occurred predominantly in the inner retinal layers. Intraperitoneal administration of minocycline significantly ameliorated retinal edema in the early stage of BRVO. We performed Full field Electroretinography (ffERG) to evaluate retinal function and found that the reduction of b wave amplitude decreased in the combined maximal response. The expressional levels of apoptosis related genes (Bax, Bcl-2) and inflammation related genes (IL-1 β, TNF α, MCP-1 and CCR2) were measured by real-time PCR, the results showed that

  1. Acute withdrawal: diagnosis and treatment.

    PubMed

    Brust, John C M

    2014-01-01

    Symptoms of alcohol withdrawal range in severity from mild "hangover" to fatal delirium tremens (DTs). Tremor, hallucinosis, and seizures usually occur within 48 hours of abstinence. Seizures tend to be generalized without focality, occurring singly or in a brief cluster, but status epilepticus is not unusual. DTs usually appears after 48 hours of abstinence and consists of marked inattentiveness, agitation, hallucinations, fluctuating level of alertness, marked tremulousness, and sympathetic overactivity. The mainstay of treatment for alcohol withdrawal is benzodiazepine pharmacotherapy, which can be used to control mild early symptoms, to prevent progression to DTs, or to treat DTs itself. Alternative less evidence-based pharmacotherapies include phenobarbital, anticonvulsants, baclofen, gamma-hydroxybutyric acid, beta-blockers, alpha-2-agonists, and N-methyl-d-aspartate receptor blockers. Treatment of DTs is a medical emergency requiring heavy sedation in an intensive care unit, with close attention to autonomic instability, fever, fluid loss, and electrolyte imbalance. Frequent comorbid disorders include hypoglycemia, liver failure, pancreatitis, sepsis, meningitis, intracranial hemorrhage, and Wernicke-Korsakoff syndrome. PMID:25307572

  2. What's New in Adult Acute Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Topic Additional resources for acute myeloid leukemia What’s new in acute myeloid leukemia research and treatment? Researchers ... benefit from current treatments. Researchers are studying many new chemo drugs for use in AML, including: Sapacitabine, ...

  3. Microbiology and treatment of acute apical abscesses.

    PubMed

    Siqueira, José F; Rôças, Isabela N

    2013-04-01

    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

  4. 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

  5. Pycnogenol treatment of acute hemorrhoidal episodes.

    PubMed

    Belcaro, Gianni; Cesarone, Maria Rosaria; Errichi, Bruno; Di Renzo, Andrea; Grossi, Maria Giovanna; Ricci, Andrea; Dugall, Mark; Cornelli, Umberto; Cacchio, Marisa; Rohdewald, Peter

    2010-03-01

    We investigated the efficacy of orally and topically applied Pycnogenol for the management of acute hemorrhoidal attacks in a controlled, randomized study with 84 subjects. Within less than 48 h of onset of an acute attack, patients were enrolled and signs and symptoms were scored. This evaluation was repeated after seven days' treatment and again seven days following treatment cessation. The decrease in scores was significantly more pronounced in the Pycnogenol-treated groups than in the control group given placebo (p < 0.05), showing the efficacy of Pycnogenol for relieving signs and symptoms of acute external hemorrhoids. In a group of patients given topical (0.5%) Pycnogenol in addition to oral Pycnogenol the improvement in symptoms set in significantly faster and was more pronounced. The most prominent symptom, hemorrhoidal bleeding, was completely absent in all patients treated with Pycnogenol for seven days and also at the 14 days follow-up. In contrast, bleedings were still observed in the control group during the two weeks follow-up. This study indicates that Pycnogenol, both in oral and in topical form, is effective for controlling this common, disabling health problem. The application of Pycnogenol eases the management of acute hemorrhoidal attacks and help avoid bleedings. PMID:20041428

  6. Analgesic effect of minocycline in rat model of inflammation-induced visceral pain.

    PubMed

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

    2014-03-15

    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 5min of administration, systemic injection of the drug produced a delayed effect (60min) 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

  7. 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

  8. Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia.

    PubMed

    Tikka, T M; Koistinaho, J E

    2001-06-15

    Glutamate excitotoxicity to a large extent is mediated through activation of the N-methyl-D-aspartate (NMDA)-gated ion channels in several neurodegenerative diseases and ischemic stroke. Minocycline, a tetracycline derivative with antiinflammatory effects, inhibits IL-1beta-converting enzyme and inducible nitric oxide synthase up-regulation in animal models of ischemic stroke and Huntington's disease and is therapeutic in these disease animal models. Here we report that nanomolar concentrations of minocycline protect neurons in mixed spinal cord cultures against NMDA excitotoxicity. NMDA treatment alone induced microglial proliferation, which preceded neuronal death, and administration of extra microglial cells on top of these cultures enhanced the NMDA neurotoxicity. Minocycline inhibited all these responses to NMDA. Minocycline also prevented the NMDA-induced proliferation of microglial cells and the increased release of IL-1beta and nitric oxide in pure microglia cultures. Finally, minocycline inhibited the NMDA-induced activation of p38 mitogen-activated protein kinase (MAPK) in microglial cells, and a specific p38 MAPK inhibitor, but not a p44/42 MAPK inhibitor, reduced the NMDA toxicity. Together, these results suggest that microglial activation contributes to NMDA excitotoxicity and that minocycline, a tetracycline derivative, represents a potential therapeutic agent for brain diseases. PMID:11390507

  9. Treatment of acute bronchiolitis with Chinese herbs.

    PubMed Central

    Kong, X T; Fang, H T; Jiang, G Q; Zhai, S Z; O'Connell, D L; Brewster, D R

    1993-01-01

    In a randomised single blind trial the Chinese herbs Shuang Huang Lian were evaluated for the treatment of acute bronchiolitis. Children with acute bronchiolitis and serological evidence of recent respiratory syncytial virus infection were studied in a tertiary hospital in Harbin, China. The 96 children were randomised into three treatment groups: herbs, herbs with antibiotics, and antibiotics alone. The herbs were prepared by the medical school pharmacy and administered daily by intravenous infusion for seven days. The main outcomes, assessed blindly, were symptomatic improvement in cough, fever, wheezing, chest signs, and duration of stay in hospital. The mean duration of symptoms from the start of treatment was 6.2 (confidence interval 5.6 to 6.9) days in the two groups treated with herbs compared with 8.6 (confidence interval 7.5 to 9.8) days in the group treated with antibiotics alone. The mean reductions in duration of clinical manifestations for treatment with antibiotics alone compared with herbs were: from 3.1 to 1.5 days for fever, 9.1 to 6.1 days for cough, 6.5 to 4.1 days for wheezing, and 7.2 to 4.9 days for chest crackles. No adverse effect of Shuang Huang Lian herbal treatment was detected. In conclusion, this study confirms Chinese experience with Shuang Huang Lian that it is safe and effective, and warrants further study. PMID:8503668

  10. Aceruloplasminemia With Psychomotor Excitement and Neurological Sign Was Improved by Minocycline (Case Report).

    PubMed

    Hayashida, Maiko; Hashioka, Sadayuki; Miki, Hiroyuki; Nagahama, Michiharu; Wake, Rei; Miyaoka, Tsuyoshi; Horiguchi, Jun

    2016-05-01

    Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin gene. Its prevalence is 1 in 2,000,000 people in Japan. This is a disorder of neurodegeneration with iron accumulation in the brain revealed by MRI. The iron overload induces oxidative stress and generation of reactive oxygen species, which triggers a cascade of pathological events that lead to neuronal death. Intravenous administration of an iron chelator, deferoxamine has been proposed as a method of inhibiting the accumulation of iron.The patient was a 46-year-old Japanese woman. She was diagnosed at the age of 33 years. Deferoxamine was administrated for 6 months but was discontinued due to adverse effects. On admission at the age of 46, psychomotor excitement was acute in onset. The extrapyramidal symptoms reflected iron deposition in the basal ganglia and substantia nigra in the midbrain. Ataxia and a wide-based gate reflected iron deposition in the dentate nuclei of the cerebellum. An antibiotic, minocycline at 150 mg/day successfully ameliorated the clinical symptoms.Minocycline, a second generation tetracycline, has a direct radical scavenging property due to its chemical structure. It has been reported that minocycline is similar to deferoxamine in its ability to chelate iron. Minocycline is also involved in preventing the upregulation of proinflammatory cytokines. The iron-chelating, antioxidant, and anti-inflammatory effects of minocycline were involved in this case. PMID:27175663

  11. Aceruloplasminemia With Psychomotor Excitement and Neurological Sign Was Improved by Minocycline (Case Report)

    PubMed Central

    Hayashida, Maiko; Hashioka, Sadayuki; Miki, Hiroyuki; Nagahama, Michiharu; Wake, Rei; Miyaoka, Tsuyoshi; Horiguchi, Jun

    2016-01-01

    Abstract Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin gene. Its prevalence is 1 in 2,000,000 people in Japan. This is a disorder of neurodegeneration with iron accumulation in the brain revealed by MRI. The iron overload induces oxidative stress and generation of reactive oxygen species, which triggers a cascade of pathological events that lead to neuronal death. Intravenous administration of an iron chelator, deferoxamine has been proposed as a method of inhibiting the accumulation of iron. The patient was a 46-year-old Japanese woman. She was diagnosed at the age of 33 years. Deferoxamine was administrated for 6 months but was discontinued due to adverse effects. On admission at the age of 46, psychomotor excitement was acute in onset. The extrapyramidal symptoms reflected iron deposition in the basal ganglia and substantia nigra in the midbrain. Ataxia and a wide-based gate reflected iron deposition in the dentate nuclei of the cerebellum. An antibiotic, minocycline at 150 mg/day successfully ameliorated the clinical symptoms. Minocycline, a second generation tetracycline, has a direct radical scavenging property due to its chemical structure. It has been reported that minocycline is similar to deferoxamine in its ability to chelate iron. Minocycline is also involved in preventing the upregulation of proinflammatory cytokines. The iron-chelating, antioxidant, and anti-inflammatory effects of minocycline were involved in this case. PMID:27175663

  12. 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. PMID:21424555

  13. [Prophylactic measures and acute treatment of migraine].

    PubMed

    Göbel, H; Heinze, A; Heinze-Kuhn, K

    2006-11-01

    The treatment of migraine consists of the acute treatment of the migraine attack and prophylactic measures for either pharmacological or non-pharmacological management. Since the retreat of the ergotamines one can only choose between one of the well-established analgesics and one of seven triptans for the treatment of the migraine attack. Although neither a new triptan nor an innovative new application form has been introduced, the year 2006 will be remembered as the year when the first triptan (naratriptan) was released as a prescription-free over-the-counter drug and when the first sumatriptan generics were marketed in Germany. In addition to the beta-blockers metoprolol and propranolol and the calcium antagonist flunarizine two antiepileptic drugs, topiramate and valproic acid, have been rated as first-line prophylactic drugs in Germany. Due to an extensive and successful study program topiramate has been officially approved in Germany. PMID:17048020

  14. Beta blocker eye drops for treatment of acute migraine.

    PubMed

    Migliazzo, Carl V; Hagan, John C

    2014-01-01

    We report seven cases of successful treatment of acute migraine symptoms using beta blocker eye drops. The literature on beta blockers for acute migraine is reviewed. Oral beta blocker medication is not effective for acute migraine treatment. This is likely due to a relatively slow rate of achieving therapeutic plasma levels when taken orally. Topical beta blocker eye drops achieve therapeutic plasma levels within minutes of ocular administration which may explain their apparent effectiveness in relief of acute migraine symptoms. PMID:25211851

  15. 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. PMID:26463975

  16. 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

  17. Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells.

    PubMed

    Ko, Jen-Chung; Wang, Tai-Jing; Chang, Po-Yuan; Syu, Jhan-Jhang; Chen, Jyh-Cheng; Chen, Chien-Yu; Jian, Yun-Ting; Jian, Yi-Jun; Zheng, Hao-Yu; Chen, Wen-Ching; Lin, Yun-Wei

    2015-10-01

    Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. Our previous studies have shown that the MKK1/2-ERK1/2 signal pathway maintains the expression of Rad51 in NSCLC cells. In this study, minocycline treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1975. Treatment with minocycline decreased Rad51 mRNA and protein levels through MKK1/2-ERK1/2 inactivation. Furthermore, expression of constitutively active MKK1 (MKK1-CA) vectors significantly rescued the decreased Rad51 protein and mRNA levels in minocycline-treated NSCLC cells. However, combined treatment with MKK1/2 inhibitor U0126 and minocycline further decreased the Rad51 expression and cell viability of NSCLC cells. Knocking down Rad51 expression by transfection with small interfering RNA of Rad51 enhanced the cytotoxicity and cell growth inhibition of minocycline. Mitomycin C (MMC) is typically used as a first or second line regimen to treat NSCLC. Compared to a single agent alone, MMC combined with minocycline resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-ERK1/2, and reduced Rad51 protein levels. Overexpression of MKK1-CA or Flag-tagged Rad51 could reverse the minocycline and MMC-induced synergistic cytotoxicity. These findings may have implications for the rational design of future drug regimens incorporating minocycline and MMC for the treatment of NSCLC. PMID:26212550

  18. 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

  19. Lipopolysaccharide-Induced Apoptosis of Astrocytes: Therapeutic Intervention by Minocycline.

    PubMed

    Sharma, Arpita; Patro, Nisha; Patro, Ishan K

    2016-05-01

    Astrocytes are most abundant glial cell type in the brain and play a main defensive role in central nervous system against glutamate-induced toxicity by virtue of numerous transporters residing in their membranes and an astrocyte-specific enzyme glutamine synthetase (GS). In view of that, a dysregulation in the astrocytic activity following an insult may result in glutamate-mediated toxicity accompanied with astrocyte and microglial activation. The present study suggests that the lipopolysaccharide (LPS)-induced inflammation results in significant astrocytic apoptosis compared to other cell types in hippocampus and minocycline could not efficiently restrict the glutamate-mediated toxicity and apoptosis of astrocytes. Upon LPS exposure 76 % astrocytes undergo degeneration followed by 44 % oligodendrocytes, 26 % neurons and 10 % microglia. The pronounced astrocytic apoptosis resulted from the LPS-induced glutamate excitotoxicity leading to their hyperactivation as evident from their hypertrophied morphology, glutamate transporter 1 upregulation and downregulation of GS. Therapeutic minocycline treatment to LPS-infused rats efficiently restricted the inflammatory response and degeneration of other cell types but could not significantly combat with the apoptosis of astrocytes. Our study demonstrates a novel finding on cellular degeneration in the hippocampus revealing more of astrocytic death and suggests a more careful consideration on the protective efficacy of minocycline. PMID:26188416

  20. Lingual hyperpigmentation associated with minocycline therapy.

    PubMed

    Meyerson, M A; Cohen, P R; Hymes, S R

    1995-02-01

    Minocycline can cause hyperpigmentation of the conjunctiva, oral mucosa, and skin. Pigmentation of the oral mucosa may also be associated with a variety of endogenous or exogenous factors. Lingual pigmentation may be seen in Addison's disease, amalgam tatoo, malignant melanoma, Peutz-Jegher's syndrome, and other diseases. Two women who had isolated pigmentation of the tongue while taking minocycline are described; no other drug-induced pigmentation of their oral mucosa or skin occurred. Minocycline-induced pigmentation should be added to the differential diagnosis of isolated lingual hyperpigmentation. PMID:7614181

  1. 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. PMID:26698398

  2. 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. PMID:25810318

  3. 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

  4. 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. PMID:24831089

  5. Treatment of acute opioid withdrawal with ibogaine.

    PubMed

    Alper, K R; Lotsof, H S; Frenken, G M; Luciano, D J; Bastiaans, J

    1999-01-01

    Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty-three cases of treatments for the indication of opioid detoxification performed in non-medical settings under open label conditions are summarized involving an average daily use of heroin of .64 +/- .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72-hour period of posttreatment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting. PMID:10506904

  6. Treatment of acute bronchospasm in urban populations.

    PubMed

    Gaines, Beverly M

    2005-12-01

    Many urban patients, including minority groups and children, continue to live in poor urban settings. Poor urban environments provide a complex mix of stressors that can exacerbate asthma and increase exacerbations. Although care is available, many minority patients have English language and communication barriers, facts that impede their access to providers and care facilities. Medications for asthma are available to these patients, and strategies to minimize stressors are in place, but implementation and delivery in an urban setting can be a problem. Asthma management strategies coupled with new formulations of asthma medications, such as levalbuterol, can significantly reduce asthma symptoms during acute bronchospasm. In addition to offering the optimal treatment for asthma, broader strategies for reducing minority disparities are required if significant inroads are to be made in addressing problems faced by urban patients. PMID:19667713

  7. 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. PMID:26551768

  8. Treatment of Sporadic Acute Puerperal Mastitis

    PubMed Central

    Barton, John R.

    1996-01-01

    Objective: The purposes of this study were to compare the efficacy of amoxicillin and cephradine for the treatment of sporadic acute puerperal mastitis (SAPM) and to evaluate the microbiology and clinical parameters of this infection. Methods: We conducted a prospective, randomized, single-blinded study comparing amoxicillin, 500 mg orally q 8 h for 7 days, and cephradine, 500 mg orally q 6 h for 7 days. The diagnostic criteria for SAPM included a temperature of ≥37.56℃ (≥99.6℉) and erythema and tenderness of the breast(s). Results: Twenty-seven consecutive outpatients with SAPM were evaluated for admission to the study, and 25 of these were enrolled. The mean temperature at enrollment was 38.17℃ (100.7℉), with a mean WBC count of 11,440/μl. The most frequent bacterial isolates from expressed milk were Staphylococcus aureus (7), staphylococcal species (coagulase negative) (8), and α-hemolytic streptococci (4). There were no significant differences between the 2 antibiotic regimens in cure rate, mean days to resolution of symptoms, or recurrence within 30 days. Both of the treatment failures and 1 of the 3 recurrences within 30 days were amoxicillin-treated patients whose cultures grew S. aureus. Conclusions: Oral amoxicillin and cephradine appear equally effective in the treatment of SAPM. Staphylococci were the most frequent isolates from the milk of women with mastitis. PMID:18476075

  9. [Pseudotumor cerebri secondary to consumption of minocycline in a pediatric patient].

    PubMed

    González Gili, Lucas O; Buffone, Ignacio R; Carrara, Laura E; Coto, María B; Fortunatti, Eliana A; Dejtera, Mabel; García Elliot, María F; Giacone, Alejandra; Luncio, Anabella C; Masnicoff, Sebastián D; Oviedo Crosta, María B; Parroua, Marianela; Romano, Mariana

    2016-04-01

    Pseudotumor cerebri is a syndrome characterized by an elevated intracranial pressure greater than 20 cmH2O with ventricles and cerebrospinal fluid of normal characteristics. Consumption of minocycline have been described among the causes associated with this syndrome. We present a 13-year old female patient with a history of acne treated with minocycline who began with severe headache, diplopia and blurred vision. The diagnosis of pseudotumor cerebri was made, indicating the immediate antibiotic suspension and the beginning of the treatment with acetazolamide. Although the pathogenesis of pseudotumor cerebri is not fully known, an association with minocycline has been observed. This antibiotic is often used by health professionals for the management of acne, so it is important to consider its complications before being prescribed. PMID:27079408

  10. Pterostilbene as treatment for severe acute pancreatitis.

    PubMed

    Lin, Y J; Ding, Y; Wu, J; Ning, B T

    2016-01-01

    Acute pancreatitis (AP) has a fast onset and progression, which lead to an unfavorable prognosis. Therefore, the development of novel drugs for its treatment is critical. As a homologous derivative of resveratrol, pterostilbene exerts a variety of effects including anti-inflammatory, antioxidant, and antitumor effects. This study investigated the potential of pterostilbene for treatment of severe AP (SAP) and related mechanisms. Effects of pterostilbene were evaluated in a Wistar rat model of AP. Serum levels of amylase (AMY), creatinine (Cr), and alanine aminotransferase (ALT) were quantified. Furthermore, serum levels of tumor necrosis factor (TNF)-a and interleukin (IL)-1b were quantified using enzyme-linked immunosorbent assay. Nuclear factor (NF)-kB expression in pancreatic tissues was quantified by real-time PCR and western blotting. The production of reactive oxygen species (ROS) was determined using a spectrometer, while superoxide dismutase (SOD) activity was assayed. In the AP rat model, the expression of inflammatory markers TNF-a and IL-1b, expression of NF-kB, and serum indices (AMY, Cr, and ALT) increased compared to the corresponding levels in the control group (P < 0.05). Pterostilbene reduced serum levels of TNF-a and IL-1b; decreased NF-kB gene expression, serum indices, and ROS generation; and increased SOD activity in a dose-dependent manner. In conclusion, pterostilbene can alleviate SAP-induced tissue damage by decreasing the inflammatory response and by promoting antioxidation leading to the protection of pancreatic tissues. PMID:27525946

  11. Endovascular treatment of acute ischemic stroke.

    PubMed

    Leslie-Mazwi, Thabele; Rabinov, James; Hirsch, Joshua A

    2016-01-01

    Endovascular thrombectomy is an effective treatment for major acute ischemic stroke syndromes caused by major anterior circulation artery occlusions (commonly referred to as large vessel occlusion) and is superior to intravenous thrombolysis and medical management. Treatment should occur as quickly as is reasonably possible. All patients with moderate to severe symptoms (National Institutes of Health stroke scale >8) and a treatable occlusion should be considered. The use of neuroimaging is critical to exclude hemorrhage and large ischemic cores. Very shortly after stroke onset (<3 hours) computed tomography (CT) and CT angiography provide sufficient information to proceed; diffusion magnetic resonance imaging (MRI) is less reliable during this early stage. After 3 hours from onset diffusion MRI is the most reliable method to define ischemic core size and should be used in centers that can offer it rapidly. Recanalization is highly effective with a stentriever or using a direct aspiration technique, with the patient awake or under conscious sedation rather than general anesthesia, if it may be performed safely. After thrombectomy the patient should be admitted to an intensive care setting and inpatient rehabilitation undertaken as soon as feasible. Patient outcomes should be assessed at 3 months, preferably using the modified Rankin score. PMID:27430469

  12. Empirical treatment of acute cystitis in women.

    PubMed

    Nicolle, Lindsay E

    2003-07-01

    Empirical antimicrobial treatment for acute cystitis in women requires continuing reassessment as the antimicrobial susceptibility of community isolates of Escherichia coli evolves. Current recommendations for 3 days trimethoprim or trimethoprim/sulphamethoxazole are compromised by increasing resistance of community E. coli to these agents. Fluoroquinolones are an alternate 3-day therapy, but increasing resistance is being reported from some countries, and widespread community use may promote resistance, limiting effectiveness of these agents for more serious infections. Alternate regimens supported by recent clinical trials suggest pivmecillinam given twice daily for 7 days is as effective as 3 days of quinolone therapy, while microbiological cure is 80% with 3 days therapy twice daily, and 90% with 3 days therapy thrice daily. Nitrofurantoin given for 7 days has a cure rate of 80-85%. Fosfomycin trometamol as a single dose has cure rates of 75-85%. All these agents are effective, but a compromise in efficacy or duration of therapy compared with current 3-day regimens may have to be considered. PMID:12842322

  13. 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

  14. [Intubation treatment of acute laryngeal obstruction: a case report].

    PubMed

    Guo, Xingguang; Liu, Shibo; Li, Huilian

    2015-11-01

    Acute laryngeal obstruction is one of the most common diseases in Department of ENT, and it can cause suffocation without prompt treatment. Methods by using Nasopharyngofiberoscope guided tracheal intubation treatment of a case of acute laryngeal obstruction patients in a timely manner. This method is well tolerated, less trauma, high success rate, in the shortest time to improve the patient's ventilation, for the next step of the treatment to win the time. PMID:26911075

  15. Hyperplastic polyps following treatment of acute gastric ulcers.

    PubMed

    Tanaka, J; Fujimoto, K; Iwakiri, R; Koyama, T; Sakata, H; Ohyama, T; Mizuguchi, M; Tokunaga, O

    1994-06-01

    Although hyperplastic polyps are the most common polyps of the stomach, the etiology of these polyps is not completely understood. We report a 61-year-old woman who developed gastric hyperplastic polyps following acute gastric lesions. She was admitted for endoscopic injection sclerotherapy of esophageal varices. After the end of sclerotherapy, acute gastric lesions developed. For treatment of the lesions, omeprazole was used for 8 weeks followed by famotidine for 8 weeks. At the end of the treatment, she developed multiple gastric hyperplastic polyps, suggesting that acute gastric lesions and/or treatment of the gastric lesions are related to the development of hyperplastic polyps in the stomach. PMID:7919626

  16. Protective effect of minocycline, a semi-synthetic second-generation tetracycline against 3-nitropropionic acid (3-NP)-induced neurotoxicity.

    PubMed

    Ahuja, Manuj; Bishnoi, Mahendra; Chopra, Kanwaljit

    2008-02-28

    3-Nitropropionic acid (3-NP) is an irreversible inhibitor of the electron transport enzyme succinate dehydrogenase, a mitochondrial Complex II enzyme. Minocycline is a semi-synthetic second-generation tetracycline with neuroprotective activity and has the capability to effectively cross the blood-brain barrier. We investigated the effects of minocycline on behavioral, biochemical, inflammation related and neurochemical alterations induced by the sub-chronic administration of 3-nitropropionic acid to rats. Chronic pre-administration of minocycline (50 and 100mg/kg) dose dependently prevented 3-NP-induced dysfunction behavioral (hypoactivity, memory retention, locomotor and rota-rod activity). In addition, 3-NP produced a marked increase in lipid peroxidation levels whereas decreased the activities of catalase and succinate dehydrogenase. In contrast, pretreatment of 3-NP injected rats with minocycline resulted in the attenuation of all these alterations. A marked increase in an inflammatory cytokine TNF-alpha by 3-NP was also decreased by minocycline treatment. Neurochemically, the administration of 3-NP significantly decreased the levels of catecholamines in the brain homogenates (dopamine, norepinephrine and serotonin) which were reversed by pretreatment of minocycline. The present finding explains the neuroprotective effect of minocycline against 3-NP toxicity by virtue of its antioxidant and anti-inflammatory activity. PMID:18164115

  17. [Thrombolytic treatment of acute myocardial infarct. 1].

    PubMed

    Soares-Costa, J T; Soares-Costa, T J; Gabriel, H M

    1998-05-01

    I-Rationale of thrombolytic therapy in acute myocardial infarction (AMI). II-Thrombolytic drugs. III-Effects of thrombolytic therapy on mortality. IV-Studies comparing the effects of various thrombolytic agents on mortality. PMID:9951051

  18. Minocycline enhances MPTP toxicity to dopaminergic neurons.

    PubMed

    Yang, Lichuan; Sugama, Shuei; Chirichigno, Jason W; Gregorio, Jason; Lorenzl, Stefan; Shin, Dong H; Browne, Susan E; Shimizu, Yoshinori; Joh, Tong H; Beal, M Flint; Albers, David S

    2003-10-15

    Minocycline has been shown previously to have beneficial effects against ischemia in rats as well as neuroprotective properties against excitotoxic damage in vitro, nigral cell loss via 6-hydroxydopamine, and to prolong the life-span of transgenic mouse models of Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). We investigated whether minocycline would protect against toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that selectively destroys nigrostriatal dopaminergic (DA) neurons and produces a clinical state similar to Parkinson's disease (PD) in rodents and primates. We found that although minocycline inhibited microglial activation, it significantly exacerbated MPTP-induced damage to DA neurons. We present evidence suggesting that this effect may be due to inhibition of DA and 1-methyl-4-phenylpridium (MPP+) uptake into striatal vesicles. PMID:14515357

  19. Acute Lymphoblastic Leukemia (ALL) Treatment in Adults (Beyond the Basics)

    MedlinePlus

    ... 2016 UpToDate, Inc. Patient information: Acute lymphoblastic leukemia (ALL) treatment in adults (Beyond the Basics) Author Richard ... the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of ...

  20. Acute dental pain, Part II: Diagnosis and emergency treatment.

    PubMed

    Antonelli, J R

    1990-09-01

    Part II of this two-part series differentiates and explores endodontic-related emergencies with reversible and irreversible pulpitis. Indications and contra-indications for vital pulp therapy are explained, and treatment is outlined. The inflammatory process involved in irreversible pulpal disease is summarized, and the clinical signs, symptoms, and treatment of irreversible pulpitis (with and without acute periradicular involvement, with pulp necrosis, and acute periradicular abscess with and without cellulitis) are discussed. PMID:2097056

  1. [Galvanic current in the conservative treatment of acute pancreatitis].

    PubMed

    Alekseenko, A V; Iftodiĭ, A G; Stoliar, V F

    1990-10-01

    Experiments were conducted on 42 adult dogs with a model of acute pancreatitis to study the degree of antibiotic storage in the pancreatic tissue in different variants of intralesional+ electrophoresis. Optimum concentration of the antibiotic was produced in transverse galvanization of the zone of the pancreas. Clinical observations over 63 patients with various forms of acute pancreatitis bear evidence that the method raises the efficacy of nonoperative treatment in the oedematous stage of the process and reduces the duration of treatment. PMID:2283730

  2. [Acute pain in children and its treatment].

    PubMed

    Dalens, B

    1991-01-01

    Pain in paediatrics has long been underestimated. The numerous scientific studies carried out during the last decade show that its existence can no longer be doubted: in fact, pain already exists during the neonatal period, and probably throughout the last trimester of gestation as well. Pain pathways mature during the embryonic period and peripheral receptors develop between the 7th and 20th week. A-delta and C fibers, as well as spinal roots and nerves, are completely differentiated before the end of the second month. The development of specific neurotransmitters and thalamic and cortical dendritic branching occurs later on; it is well enough developed to allow perception of painful stimuli (slow or protopathic component) from the beginning of the foetal period onwards. The discriminative rapid component develops in parallel to myelinisation, and the psycho-affective component, which requires a long and complex learning process, will not be fully operative until the end of puberty. Assessing pain, already a difficult task in the adult, is all the more so in children because of lesser verbal communicative capabilities, difficulty in handling abstract concepts, lack of experience of painful stimuli to make comparisons, and ignorance of their body image. In the very young child, diagnosing pain relies on suggestive circumstances, and an altered behaviour, knowing that no one symptom in pathognomonic. As the child grows up, methods for self-assessment of pain become usable, such as coloured scales and simplified verbal scales. However, behavioural tests remain the mainstay until the prepubertal period. The treatment of acute pain requires a reasoned approach which takes into account the state of the child, that of the aetiological investigations, the likely course of the lesions, as well as the patient's analgesic requirements. Therapeutic means do not differ from those for adult patients; however, the differences of distribution of body water, the small

  3. Colon Cancer After Acute Diverticulitis Treatment

    PubMed Central

    Oh, Kwang Hoon; Kim, Eun Jung; Lee, Je Hoon; Choi, Kyu Un; Han, Myung Sik; Ahn, Jae Hong; Cheon, Gab Jin

    2013-01-01

    Diverticulitis is the most common clinical complication of diverticular disease, affecting 10-25% of the patients with diverticula. The prevalences of diverticulitis and colon cancer tend to increase with age and are higher in industrialized countries. Consequently, diverticulitis and colon cancer have been reported to have similar epidemiological characteristics. However, the relationship between these diseases remains controversial, as is the performance of routine colonoscopy after an episode of diverticulitis to exclude colon cancer. Recently, we experienced three cases of colon cancer after treating acute diverticulitis, based on which we suggest the importance of follow-up colonoscopy after acute diverticulitis. PMID:24032118

  4. Imipenem/cilastatin-induced acute eosinophilic pneumonia.

    PubMed

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

    2016-01-01

    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. PMID:26944380

  5. 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

  6. A novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline inhibits nociception and oedema in mice

    PubMed Central

    Bastos, L F S; Angusti, A; Vilaça, M C; Merlo, L A; Nascimento, E B; Rocha, L T S; Godin, A M; Solano, A G R; Jarussophon, S; Nunan, E A; Konishi, Y; Coelho, M M

    2008-01-01

    Background and purpose: Many in vitro and fewer in vivo studies have shown that tetracyclines present anti-inflammatory activity. We investigated if a novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline, 12S-hydroxy-1,12-pyrazolinominocycline (PMIN), also induced antinociceptive and anti-inflammatory effects. Experimental approach: Antibacterial effects against a minocycline-sensitive Staphylococcus aureus strain were evaluated by applying a cylinder-plate agar diffusion technique. Antibacterial effects of diluted serum from mice pre-treated with minocycline or PMIN were also evaluated. Ca2+ binding activity was assessed by spectrophotometry. Formalin-induced nociceptive responses and carrageenan-induced paw oedema were evaluated in mice. The rota-rod apparatus was used to evaluate motor coordination. Key results: Minocycline, but not PMIN, inhibited bacterial growth. Serum from mice treated with minocycline, but not with PMIN, also induced such an effect. The UV absorption spectrum of solutions of minocycline, but not those of PMIN, was markedly changed in the presence of Ca2+. Minocycline or PMIN inhibited both phases of formalin-induced nociception and carrageenan-induced paw oedema. It is unlikely that antinociception resulted from lack of motor coordination, as tetracycline did not impair the performance of mice on the rotating rod. Conclusions and implications: These results indicate that inhibition of nociception and oedema by tetracyclines is neither necessarily linked to antibacterial nor to Ca2+chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the treatment of painful and inflammatory diseases, as its lack of antibacterial and Ca2+chelating activities might confer greater safety over conventional tetracyclines. PMID:18660827

  7. Assessment of Minocycline and Polymyxin B Combination against Acinetobacter baumannii

    PubMed Central

    Bowers, Dana R.; Cao, Henry; Zhou, Jian; Ledesma, Kimberly R.; Sun, Dongxu; Lomovskaya, Olga

    2015-01-01

    Antimicrobial resistance among Acinetobacter baumannii is increasing worldwide, often necessitating combination therapy. The clinical utility of using minocycline with polymyxin B is not well established. In this study, we investigated the activity of minocycline and polymyxin B against 1 laboratory isolate and 3 clinical isolates of A. baumannii. Minocycline susceptibility testing was performed with and without an efflux pump inhibitor, phenylalanine-arginine β-naphthylamide (PAβN). The intracellular minocycline concentration was determined with and without polymyxin B (0.5 μg/ml). Time-kill studies were performed over 24 h using approximately 106 CFU/ml of each strain with clinically relevant minocycline concentrations (2 μg/ml and 8 μg/ml), with and without polymyxin B (0.5 μg/ml). The in vivo efficacy of the combination was assessed in a neutropenic murine pneumonia model. Infected animals were administered minocycline (50 mg/kg), polymyxin B (10 mg/kg), or both to achieve clinically equivalent exposures in humans. A reduction in the minocycline MIC (≥4×) was observed in the presence of PAβN. The intracellular concentration and in vitro bactericidal effect of minocycline were both enhanced by polymyxin B. With 2 minocycline-susceptible strains, the bacterial burden in lung tissue at 24 h was considerably reduced by the combination compared to monotherapy with minocycline or polymyxin B. In addition, the combination prolonged survival of animals infected with a minocycline-susceptible strain. Polymyxin B increased the intracellular concentration of minocycline in bacterial cells and enhanced the bactericidal activity of minocycline, presumably due to efflux pump disruption. The clinical utility of this combination should be further investigated. PMID:25712362

  8. Chronic Alcohol Intoxication and Cortical Ischemia: Study of Their Comorbidity and the Protective Effects of Minocycline

    PubMed Central

    Fernandes, Luanna Melo Pereira; Gomes-Leal, Walace; Lima, Rafael Rodrigues; Prediger, Rui Daniel; Crespo-López, Maria Elena

    2016-01-01

    Chronic alcohol intoxication (CAI) increases both morbidity and mortality of stroke patients. Despite the high prevalence of CAI and ischemic stroke, studies addressing their comorbidity and/or protective alternatives remain scarce. Thus, the influence of CAI on both stroke outcome and minocycline treatment (recognized for its neuroprotective effect) was investigated. Female Wistar rats (35 days old) were treated with water or ethanol (6.5 g/kg/day, 22.5% w/v) for 55 days. Then, focal ischemia was induced by endothelin-1 in the motor cortex. Two hours later, four doses of 50 mg/kg of minocycline every 12 hours followed by five doses of 25 mg/kg every 24 hours were administered. Behavioral performance (open field and rotarod tests) and immunohistochemical (cellular density, neuronal death, and astrocytic activation) and biochemical (lipid peroxidation and nitrite levels) analyses were performed. CAI increased motor disruption, nitrite and lipid peroxidation levels, and neuronal loss caused by ischemia, whereas it reduced the astrogliosis. Minocycline was effective in preventing the motor and tissue damage caused by stroke. However, these effects were attenuated when CAI preceded stroke. Our data suggest that CAI beginning in adolescence contributes to a worse outcome in ischemic stroke survivors and reduces the benefits of minocycline, possibly requiring adjustments in therapy. PMID:27418952

  9. Macrophages-mediated neurotoxic effects of intra-nigral manganese administration are attenuated by minocycline.

    PubMed

    Ponzoni, Silvia

    2012-01-01

    The present study was designed to address the role of macrophages in Mn-induced neurotoxicity and to test the hypothesis that minocycline, a tetracycline derivative, attenuates the biochemical and morphological sequelae of Mn. Mn was unilaterally microinjected into rat nigra followed by systemic minocycline or saline administration 24h later, daily for 3 days. At 72h after the intranigral Mn microinjection, tyrosine hydroxylase immunostaining (TH-IS) was evaluated in the striatum, along with the number of macrophages (as indicated by CD11b immunostaining) in the substantia nigra. Mn significantly reduced striatal TH-IS, and causes an increased macrophage number at the lesion site when compared with the control group. The effects of Mn on striatal TH-IS and the number of macrophages at the lesion site were concentration dependent. Consistent with the stated hypothesis, minocycline significantly reduced the macrophage number in the lesion site and minimized the TH-IS striatal loss induced by Mn. These results indicate that an inflammatory response mediated by macrophages is induced by intranigral Mn microinjection, which is fully attenuated by minocycline treatment, suggesting that suppression of macrophage infiltration provides neuroprotection to dopaminergic neurons. PMID:22085690

  10. Hypoxia-induced neuroinflammatory white-matter injury reduced by minocycline in SHR/SP

    PubMed Central

    Jalal, Fakhreya Y; Yang, Yi; Thompson, Jeffrey F; Roitbak, Tamara; Rosenberg, Gary A

    2015-01-01

    Hypertensive small vessel disease is a major cause of vascular cognitive impairment (VCI). Spontaneously hypertensive/stroke prone rats (SHR/SP) with unilateral carotid artery occlusion (UCAO) and a Japanese permissive diet (JPD) have white-matter (WM) damage similar to that seen in VCI. We hypothesized that WM injury was due to hypoxia-mediated, blood–brain barrier (BBB) disruption. Twelve-week-old SHR/SP had UCAO/JPD and were studied with immunohistochemistry, biochemistry, multimodal magnetic resonance imaging (MRI), and Morris water maze (MWM) testing. One week after UCAO/JPD, WM showed a significant increase in hypoxia inducible factor-1α (HIF-1α), which increased further by 3 weeks. Prolyl hydroxylase-2 (PHD2) expression decreased at 1 and 3 weeks. Infiltrating T cells and neutrophils appeared around endothelial cells from 1 to 3 weeks after UCAO/JPD, and matrix metalloproteinase-9 (MMP-9) colocalized with inflammatory cells. At 3 weeks, WM immunostained for IgG, indicating BBB leakage. Minocycline (50 mg/kg intraperitoeally) was given every other day from weeks 12 to 20. Multimodal MRI showed that treatment with minocycline significantly reduced lesion size and improved cerebral blood flow. Minocycline improved performance in the MWM and prolonged survival. We propose that BBB disruption occurred secondary to hypoxia, which induced an MMP-9-mediated infiltration of leukocytes. Minocycline significantly reduced WM damage, improved behavior, and prolonged life. PMID:25712499

  11. Hypoxia-induced neuroinflammatory white-matter injury reduced by minocycline in SHR/SP.

    PubMed

    Jalal, Fakhreya Y; Yang, Yi; Thompson, Jeffrey F; Roitbak, Tamara; Rosenberg, Gary A

    2015-07-01

    Hypertensive small vessel disease is a major cause of vascular cognitive impairment (VCI). Spontaneously hypertensive/stroke prone rats (SHR/SP) with unilateral carotid artery occlusion (UCAO) and a Japanese permissive diet (JPD) have white-matter (WM) damage similar to that seen in VCI. We hypothesized that WM injury was due to hypoxia-mediated, blood-brain barrier (BBB) disruption. Twelve-week-old SHR/SP had UCAO/JPD and were studied with immunohistochemistry, biochemistry, multimodal magnetic resonance imaging (MRI), and Morris water maze (MWM) testing. One week after UCAO/JPD, WM showed a significant increase in hypoxia inducible factor-1α (HIF-1α), which increased further by 3 weeks. Prolyl hydroxylase-2 (PHD2) expression decreased at 1 and 3 weeks. Infiltrating T cells and neutrophils appeared around endothelial cells from 1 to 3 weeks after UCAO/JPD, and matrix metalloproteinase-9 (MMP-9) colocalized with inflammatory cells. At 3 weeks, WM immunostained for IgG, indicating BBB leakage. Minocycline (50 mg/kg intraperitoneally) was given every other day from weeks 12 to 20. Multimodal MRI showed that treatment with minocycline significantly reduced lesion size and improved cerebral blood flow. Minocycline improved performance in the MWM and prolonged survival. We propose that BBB disruption occurred secondary to hypoxia, which induced an MMP-9-mediated infiltration of leukocytes. Minocycline significantly reduced WM damage, improved behavior, and prolonged life. PMID:25712499

  12. A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons.

    PubMed

    Orio, Laura; Llopis, Noemi; Torres, Elisa; Izco, Maria; O'Shea, Esther; Colado, M Isabel

    2010-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1beta). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFkappaB binding activity, 3 h later for the determination of IL-1beta, 24 h later for the determination of microglial activation or 7 days later for the determination of [(3)H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFkappaB activation, IL-1beta release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFkappaB activation, IL-1beta release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFkappaB activation, IL-1beta release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFkappaB activation possibly through a reduction in IL-1beta signalling. PMID:19777321

  13. Extracorporeal photopheresis in prevention and treatment of acute GVHD.

    PubMed

    Kitko, Carrie L; Levine, John E

    2015-04-01

    Acute graft versus host disease (GVHD), a common complication after allogeneic hematopoietic cell transplantation (HCT), occurs in as many as 70% of recipients of this life saving treatment. Front line therapy for GVHD with corticosteroids will fail in up to 40% of patients, which leads to high morbidity and mortality. Traditional prevention and treatment strategies have focused on reducing alloreactivity, typically with therapy to reduce cytotoxic T-cell function. Emerging evidence exists that promotion of regularly T-cell function, through treatments such as extracorporeal photopheresis, is effective for GVHD treatment and has potential for prevention as well. This review will focus on literature reporting the success of ECP for steroid refractory acute GVHD and the potential for delivery of ECP in the early pre and post-transplant periods that shows promise as a less immunosuppressive strategy to reduce rates of acute GVHD. PMID:25748231

  14. What do patients want from acute migraine treatment?

    PubMed

    Gallagher, Rm

    2004-01-01

    Clinical observations have shown that migraine is a progressive disorder, both within an acute attack, and within the disease itself. Rates of diagnosis for migraine have increased in the last decade, but more than half of migraineurs remain undiagnosed. Patient expectations of migraine therapies have also increased (patients require rapid and sustained pain relief with a treatment that has good tolerability), and can differ greatly from those of physicians. Management decisions should be made with these expectations in mind, to enhance patient outcomes and compliance with treatment. Improved understanding of acute migraine attack pathophysiology has led to the strategy of early treatment to modify both the progression of the current attack and, potentially, the progression of the disease itself in the individual. The triptans are effective acute migraine therapies. Each agent has its own distinct profile of efficacy and tolerability, enabling individualization of treatment. PMID:15595989

  15. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed. PMID:27018033

  16. 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.…

  17. Treatment of acute silicoproteinosis by whole-lung lavage.

    PubMed

    Stafford, Marshall; Cappa, Anthony; Weyant, Michael; Lara, Abigail; Ellis, James; Weitzel, Nathaen S; Puskas, Ferenc

    2013-06-01

    Acute silicoproteinosis is a rare disease that occurs following a heavy inhalational exposure to silica dusts. Clinically, it resembles pulmonary alveolar proteinosis (PAP); silica exposure is thought to be a cause of secondary PAP. We describe a patient with biopsy-confirmed acute silicoproteinosis whose course was complicated by acute hypoxemic respiratory failure requiring mechanical ventilation. Without clinical improvement despite antibiotic and steroid treatment, the patient was scheduled for whole-lung lavage under general anesthesia. Anesthetic challenges included double-lumen tube placement and single-lung ventilation in a hypoxic patient, facilitating lung lavage, and protecting the contralateral lung from catastrophic spillage. PMID:23632425

  18. Minocycline Attenuates Iron Neurotoxicity in Cortical Cell Cultures

    PubMed Central

    Chen-Roetling, Jing; Chen, Lifen; Regan, Raymond F.

    2009-01-01

    Iron neurotoxicity may contribute to the pathogenesis of intracerebral hemorrhage (ICH). The tetracycline derivative minocycline is protective in ICH models, due putatively to inhibition of microglial activation. Although minocycline also chelates iron, its effect on iron neurotoxicity has not been reported, and was examined in this study. Cortical cultures treated with 10 μM ferrous sulfate for 24h sustained loss of most neurons and an increase in malondialdehyde. Minocycline prevented this injury, with near-complete protection at 30 μM. Two other inhibitors of microglial activation, doxycycline and macrophage/microglia inhibitory factor, were ineffective. Oxidation of isolated culture membranes by iron was also inhibited by minocycline. Consistent with prior observations, minocycline chelated iron in a siderophore colorometric assay; at concentrations less than 100 μM, its activity exceeded that of deferoxamine. These results suggest that attenuation of iron neurotoxicity may contribute to the beneficial effect of minocycline in hemorrhagic stroke and other CNS injury models. PMID:19523448

  19. Coadministration of indomethacin and minocycline attenuates established paclitaxel-induced neuropathic thermal hyperalgesia: Involvement of cannabinoid CB1 receptors

    PubMed Central

    Parvathy, Subramanian S.; Masocha, Willias

    2015-01-01

    Taxanes such as paclitaxel, which are chemotherapeutic drugs, cause dose-dependent painful neuropathy in some patients. We investigated whether coadministration of minocycline and indomethacin produces antinociceptive effects in mice with paclitaxel-induced neuropathic thermal hyperalgesia and if the cannabinoid system is involved. Previously, we reported that coadministration of these two drugs results in antinociception against inflammatory pain at doses where either drug alone lack significant activity. In the current study, we observed that treatment of female mice with indomethacin or minocycline alone did not affect established paclitaxel-induced thermal hyperalgesia, whereas coadministration of the two drugs attenuated it. In male mice indomethacin had some antihyperalgesic activity, whilst minocycline did not. Coadministration of the two drugs had supraadditive antihyperalgesic activity in male mice. Administration of a cannabinoid CB1 receptor antagonist AM 251 blocked the antihyperalgesic effects of the combination of minocycline and indomethacin in both male and female mice. In conclusion our results indicate that coadministration of minocycline and indomethacin abrogates established paclitaxel-induced neuropathic thermal hyperalgesia in mice, and the potentiation of the antinociceptive effects of this combination involves the cannabinoid system. PMID:26085115

  20. Coadministration of indomethacin and minocycline attenuates established paclitaxel-induced neuropathic thermal hyperalgesia: Involvement of cannabinoid CB1 receptors.

    PubMed

    Parvathy, Subramanian S; Masocha, Willias

    2015-01-01

    Taxanes such as paclitaxel, which are chemotherapeutic drugs, cause dose-dependent painful neuropathy in some patients. We investigated whether coadministration of minocycline and indomethacin produces antinociceptive effects in mice with paclitaxel-induced neuropathic thermal hyperalgesia and if the cannabinoid system is involved. Previously, we reported that coadministration of these two drugs results in antinociception against inflammatory pain at doses where either drug alone lack significant activity. In the current study, we observed that treatment of female mice with indomethacin or minocycline alone did not affect established paclitaxel-induced thermal hyperalgesia, whereas coadministration of the two drugs attenuated it. In male mice indomethacin had some antihyperalgesic activity, whilst minocycline did not. Coadministration of the two drugs had supraadditive antihyperalgesic activity in male mice. Administration of a cannabinoid CB1 receptor antagonist AM 251 blocked the antihyperalgesic effects of the combination of minocycline and indomethacin in both male and female mice. In conclusion our results indicate that coadministration of minocycline and indomethacin abrogates established paclitaxel-induced neuropathic thermal hyperalgesia in mice, and the potentiation of the antinociceptive effects of this combination involves the cannabinoid system. PMID:26085115

  1. Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV seropositive individuals with cognitive impairment

    PubMed Central

    Sacktor, Ned; Miyahara, Sachiko; Evans, Scott; Schifitto, Giovanni; Cohen, Bruce; Haughey, Norman; Drewes, Julia L.; Graham, David; Zink, M. Christine; Anderson, Caroline; Nath, Avindra; Pardo, Carlos A.; McCarthy, Sean; Hosey, Lara; Clifford, David

    2014-01-01

    Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation, and decreased neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, “Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-associated Cognitive Impairment”, minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, neurotransmitter levels, and inflammation from CSF in participants in A5235. 107 HIV+ individuals received either minocycline 100 mg or placebo orally every 12 hours for 24 weeks. 21 HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers. These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results. PMID:25377444

  2. 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. PMID:26745749

  3. Antipsychotic-like effect of minocycline in a rat model

    PubMed Central

    Dokuyucu, Recep; Kokacya, Hanifi; Inanir, Sema; Copoglu, Umit Sertan; Erbas, Oytun

    2014-01-01

    Objectives: Tetracycline antibiotic drug minocycline has strongly neuroprotective and anti-inflammatory effects. Minocycline has also remarkable brain tissue penetration, is clinically entirely tolerated and properly absorbed when taken orally. In our study, we class with the effects of minocycline and chlorpromazine, a conventional antipsychotic drug, by evaluating the novelty-induced rearing, apomorphine-induced stereotypic behavior, and brain MDA levels in rats. Materials and Methods: Four groups of rat (n = 7) were applied with minocycline (50 and 100 mg/kg, i.p.), chlorpromazine (1 mg/kg, i.p.), or isotonic saline (1 mL/kg, i.p.). One hour later, apomorphine (2 mg/kg, s.c.) was applied to each rat. Result: Our results showed that both doses of minocycline significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. Minocycline also decreased the stereotypy scores in a dose-dependent manner. Conclusion: We concluded that minocycline has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, minocycline, as an anti-oxidant and cytoprotective agent, can be useful in neuroprotection especially on early stages of psychosis or prepsychotic patients with insignificant symptoms. Minocycline is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug. PMID:25419368

  4. Faropenem medoxomil: a treatment option in acute bacterial rhinosinusitis.

    PubMed

    Hadley, James A; Tillotson, Glenn S; Tosiello, Robert; Echols, Roger M

    2006-12-01

    Faropenem medoxomil is the first oral penem in a new class of beta-lactam antibiotics. Faropenem medoxomil has excellent in vitro activity against Streptococcus pneumoniae, Haemophilus influenzae and other key pathogens implicated in acute bacterial rhinosinusitis. Clinical studies have demonstrated that, in the treatment of acute bacterial rhinosinusitis in adults, 7 days of treatment with faropenem medoxomil is as clinically and bacteriologically effective as 10 days of treatment with cefuroxime axetil. One study showed faropenem medoxomil to be superior to cefuroxime axetil. Overall, the safety profile of faropenem medoxomil is similar to that of most comparators. Specifically, the minimal impact of faropenem medoxomil on the gastrointestinal flora leads to less diarrhea and other adverse events than coamoxicillin-clavulanate. Faropenem medoxomil has almost no drug-drug interactions and little requirement for dosage adjustments in the typical acute rhinosinusitis population. PMID:17181408

  5. Comparison of two main treatment modalities for acute ankle sprain

    PubMed Central

    Bilgic, Serkan; Durusu, Murat; Aliyev, Bahtiyar; Akpancar, Serkan; Ersen, Omer; Yasar, S.Mehmet; Ardic, Sukru

    2015-01-01

    Objective: Acute ankle sprains are one of the most common injuries in emergency departments. Immobilization is widely accepted as the basic treatment modality for acute ankle sprains; however, immobilization method remains controversial. In this study, we aimed to compare two treatment modalities: splint and elastic bandage for the management of acute ankle sprains. Methods: This prospective study was conducted in the emergency department. Fifty-one consecutive patients who were admitted to the emergency department owing to the complaint of ankle sprain and who were treated with an elastic bandage or a splint were included in the study. After bone injury was ruled out, treatment choice was left to the on-shift physicians’ discretion. The extent of edema was evaluated before and after the treatment by using a small, graduated container filled with warm water. Volume differences were calculated by immersing both lower extremities in a container filled to a constant level. Pain was evaluated using the visual analogue scale. Results: There were 25 patients in the elastic bandage group and 26 patients in the splint group. VAS scores of these groups before and after the treatment were similar. Although edema size before and after the treatment were similar between the groups, edema size reduction was significantly more in the elastic bandage group [p=0,025]. Conclusions: This study showed that treatment of acute ankle sprains with an elastic bandage was more effective than splint in reducing edema. Therefore, an elastic bandage could be preferred over a splint for the treatment of acute ankle sprains. PMID:26870123

  6. Diagnosis and treatment of acute extremity compartment syndrome.

    PubMed

    von Keudell, Arvind G; Weaver, Michael J; Appleton, Paul T; Appelton, Paul T; Bae, Donald S; Dyer, George S M; Heng, Marilyn; Jupiter, Jesse B; Vrahas, Mark S

    2015-09-26

    Acute compartment syndrome of the extremities is well known, but diagnosis can be challenging. Ineffective treatment can have devastating consequences, such as permanent dysaesthesia, ischaemic contractures, muscle dysfunction, loss of limb, and even loss of life. Despite many studies, there is no consensus about the way in which acute extremity compartment syndromes should be diagnosed. Many surgeons suggest continuous monitoring of intracompartmental pressure for all patients who have high-risk extremity injuries, whereas others suggest aggressive surgical intervention if acute compartment syndrome is even suspected. Although surgical fasciotomy might reduce intracompartmental pressure, this procedure also carries the risk of long-term complications. In this paper in The Lancet Series about emergency surgery we summarise the available data on acute extremity compartment syndrome of the upper and lower extremities in adults and children, discuss the underlying pathophysiology, and propose a clinical guideline based on the available data. PMID:26460664

  7. [Treatment of the acute diverticulitis: A systematic review].

    PubMed

    Dréanic, Johann; Sion, Elena; Dhooge, Marion; Dousset, Bertrand; Camus, Marine; Chaussade, Stanislas; Coriat, Romain

    2015-11-01

    Acute diverticulitis is a common disease with increasing incidence. In most of cases, diagnosis is made at an uncomplicated stage offering a curative attempt under medical treatment and use of antibiotics. There is a risk of diverticulitis recurrence. Uncomplicated diverticulitis is opposed to complicated forms (perforation, abscess or fistula). Recent insights in the pathophysiology of diverticulitis, the natural history, and treatments have permitted to identify new treatment strategies. For example, the use of antibiotics tends to decrease; surgery is now less invasive, percutaneous drainage is preferred, peritoneal lavage is encouraged. Treatments of the diverticulitis are constantly evolving. In this review, we remind the pathophysiology and natural history, and summarize new recommendations for the medical and surgical treatment of acute diverticulitis. PMID:26358668

  8. Pivmecillinam for the treatment of acute uncomplicated urinary infection.

    PubMed

    Nicolle, L E

    1999-12-01

    Pivmecillinam is a beta-lactam antimicrobial marketed almost two decades ago. It has been used widely for the treatment of acute cystitis in selected areas of the world, particularly in Scandinavia. With increasing resistance of community Escherichia coli isolates to trimethoprim and trimethoprim/sulphamethoxazole, as previously observed for ampicillin and sulphonamides, reassessment of empiric antimicrobial regimens for acute uncomplicated urinary infection is necessary. Thus, it is timely to revisit the role of pivmecillinam for the treatment of acute cystitis. Clinical studies document the efficacy of this antimicrobial with short course therapy for acute cystitis, and clinical practice in countries where it has been used for many years confirms its efficacy and tolerability. If this agent were more widely used for empiric treatment for acute cystitis, use of antimicrobials such as the quinolones might be avoided. Further trials to define the comparative efficacy of pivmecillinam with other antimicrobials, and further studies of community resistance in E. coli isolates to this agent are needed. PMID:10692756

  9. Pulmonary function after treatment for acute lymphoblastic leukaemia in childhood.

    PubMed Central

    Nysom, K.; Holm, K.; Olsen, J. H.; Hertz, H.; Hesse, B.

    1998-01-01

    The aim of this study was to examine pulmonary function after acute lymphoblastic leukaemia in childhood and identify risk factors for reduced pulmonary function. We studied a population-based cohort of 94 survivors of acute lymphoblastic leukaemia in childhood who were in first remission after treatment without spinal irradiation or bone marrow transplantation. Pulmonary function test results were compared with reference values for our laboratory, based on 348 healthy subjects who had never smoked from a local population study. A median of 8 years after cessation of therapy (range 1-18 years) the participants had a slight, subclinical, restrictive ventilatory insufficiency and reduced transfer factor and transfer coefficient. The changes in lung function were related to younger age at treatment and to more dose-intensive treatment protocols that specified more use of cranial irradiation and higher cumulative doses of anthracyclines, cytosine arabinoside and intravenous cyclophosphamide than previous protocols. We conclude that, 8 years after treatment without bone marrow transplantation or spinal irradiation, survivors of childhood acute lymphoblastic leukaemia in first remission were without pulmonary symptoms but had signs of slight restrictive pulmonary disease including reduced transfer factor. The increased dose intensity of many recent protocols for childhood acute lymphoblastic leukaemia may lead to increased late pulmonary toxicity. PMID:9662245

  10. Epidemiology and Treatment of Acute Promyelocytic Leukemia in Latin America

    PubMed Central

    Rego, E.M.; Jácomo, R.H.

    2011-01-01

    Distinct epidemiological characteristics have been described in Acute Promielocytic Leukemia (APL). Populations from Latin America have a higher incidence of APL and in some geographic areas a distinct distribution of the PML-RARA isoforms is present. Here, we review the main differences in APL epidemilogy in Latin America as well as treatment outcomes. PMID:22110899

  11. Treatment strategies for acute metabolic disorders in neonates

    PubMed Central

    Mohamed, Sarar

    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.

  12. Treatment of acute bronchospasm in elderly patients.

    PubMed

    Berger, William E

    2005-12-01

    Both asthma and chronic obstructive pulmonary disease (COPD) are often underdiagnosed and undertreated among the elderly. Patient compliance with treatments plans and medication schedules are often less than ideal. This paper presents results from clinical studies examining levalbuterol and racemic albuterol use among elderly patients who have asthma or COPD. PMID:19667714

  13. Endovascular Treatment of Acute Thrombosis of Cerebral Veins and Sinuses

    PubMed Central

    Yakovlev, Sergey Borisovich; Bocharov, Aleksei Vasilievich; Mikeladze, Ketevan; Gasparian, Sergey Surenovich; Serova, Natalia Konstantinovna; Shakhnovich, Alexander Romanovich

    2014-01-01

    Summary Acute thrombosis of cerebral veins and sinuses (ATCVS) is a multifactorial disease with grave consequences. Because of its rare occurrence there are no proven treatment guidelines. Sixteen patients with ATCVS were treated. The final diagnosis was confirmed by digital subtraction angiography. Sinus catheterization was performed via transfemoral venous access. Treatment included mechanical manipulation of thrombi and thrombolytic therapy. A regression of clinical symptoms with a concomitant decrease of intracranial hypertension was achieved in all patients. Long-term results were studied in eight patients: none presented clinical signs of intracranial hypertension. Endovascular transvenous recanalization is an effective treatment for acute thrombosis of cerebral veins and sinuses. Along with the local thrombolysis, significant potential in the treatment of this complex pathology lies in the transvenous endovascular techniques of mechanical thrombus extraction, especially in patients with intracranial hemorrhage for whom the use of thrombolytic agents is restricted. PMID:25196622

  14. Acute behavioral interventions and outpatient treatment strategies with suicidal adolescents

    PubMed Central

    O’Brien, Kimberly H. McManama; Singer, Jonathan B.; LeCloux, Mary; Duarté-Vélez, Yovanska; Spirito, Anthony

    2015-01-01

    Despite the prevalence of suicidal thoughts and behaviors among adolescents, there is limited knowledge of effective interventions to use with this population. This paper reviews the findings of studies on behavioral interventions for adolescents who are at acute suicide risk, as well as outpatient treatment and risk management strategies with suicidal adolescents. The importance of addressing comorbid behaviors and enhancing protective factors are discussed. Cultural considerations in working with suicidal adolescents and strategies for conducting culturally competent treatment are explored. PMID:26279646

  15. Acute treatment of anaphylaxis in children

    PubMed Central

    Goldman, Ran D.

    2013-01-01

    Abstract Question A 3-year-old was rushed to my office after eating a friend’s chocolate bar that contained nuts. He immediately developed urticaria on his face and swelling of his lips, and he had a persistent cough. What is the best treatment for a child with anaphylaxis? Should this family receive a prescription for an epinephrine autoinjector device? Answer Intramuscular epinephrine injection is a safe and effective treatment of anaphylaxis in children. Children with systemic allergic reactions should carry epinephrine autoinjectors at all times, and should certainly have one with them at school. In order for epinephrine autoinjectors to be effective, children and their families need to be educated on how to properly use the devices, as well as keep in mind the product’s expiration date. PMID:23851537

  16. Minocycline inhibits PARP-1 expression and decreases apoptosis in diabetic retinopathy

    PubMed Central

    WU, YING; CHEN, YONGDONG; WU, QIANG; JIA, LILI; DU, XINHUA

    2015-01-01

    The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy-associated cellular apoptosis. A total of 40 Sprague Dawley (SD) rats were used as a diabetic retinopathy model following injection with streptozotocin. Among the 34 rats in which the diabetes model was successfully established, 24 rats were divided into two experimental groups: I and II (T1 and T2, respectively), and orally administered with various doses of minocycline. The remaining 10 rats served as the diabetic retinopathy control group. An additional group of 10 healthy SD rats with comparable weight served as normal controls. The rats in T1 and T2 groups were treated daily for eight consecutive weeks with minocycline at a dose of 2.5 mg/kg and 5 mg/kg, respectively. The mRNA expression levels of poly (ADP-ribose) polymerase-1 (PARP-1) were subsequently measured by reverse transcription-quantitative polymerase chain reaction, and the protein expression levels of poly-ADP-ribose were measured by western blot analysis and immunohistochemistry. Retinal morphology was observed following hematoxylin and eosin staining, and retinal cell apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase-3 activity assays. The amplitudes of the electroretinogram (ERG) b-wave and oscillary potentials (OPs) were measured using visual electrophysiology, and compared among the four groups. The results of the present study demonstrated that in the diabetic rats, retinal PARP-1 gene expression was markedly upregulated, the number of apoptotic cells and the activity levels of caspase-3 were increased, and the amplitude of the ERG b-wave and the OPs were markedly lower as compared with the normal rats. Following treatment with minocycline, the abnormal expression of PARP-1 in the retina was inhibited, and cellular apoptosis was decreased. In conclusion, the results of the present study suggest that PARP-1 is involved in the

  17. Hyperpigmentation of the skin associated with minocycline therapy

    SciTech Connect

    Gordon, G.; Sparano, B.M.; Iatropoulos, M.J.

    1985-05-01

    Skin biopsy specimens and discolored fingernails from minocycline-treated patients were examined by light and electron microscopy, histochemistry, and energy-dispersive x-ray analysis. Both hyperpigmented and adjacent normally pigmented skin samples contained pigment-laden macrophages in the dermis, although these cells were more numerous in the hyperpigmented skin samples. Elemental analysis showed that both pigment deposits and stratum corneum of hyperpigmented skin samples contained iron and calcium. Discolored areas of fingernails from a minocycline-treated patient also contained iron and calcium. Both skin and nail discoloration were possibly due to the presence of an iron chelate of minocycline and/or quinoid derivatives of minocycline. The presence of iron-containing pigment in normal as well as hyperpigmented skin may have predisposed to formation of minocycline-associated pigment in these patients.

  18. 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

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

    PubMed

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

    2013-09-18

    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

  20. Minimally Invasive Surgical Treatment of Acute Epidural Hematoma: Case Series

    PubMed Central

    2016-01-01

    Background and Objective. Although minimally invasive surgical treatment of acute epidural hematoma attracts increasing attention, no generalized indications for the surgery have been adopted. This study aimed to evaluate the effects of minimally invasive surgery in acute epidural hematoma with various hematoma volumes. Methods. Minimally invasive puncture and aspiration surgery were performed in 59 cases of acute epidural hematoma with various hematoma volumes (13–145 mL); postoperative follow-up was 3 months. Clinical data, including surgical trauma, surgery time, complications, and outcome of hematoma drainage, recovery, and Barthel index scores, were assessed, as well as treatment outcome. Results. Surgical trauma was minimal and surgery time was short (10–20 minutes); no anesthesia accidents or surgical complications occurred. Two patients died. Drainage was completed within 7 days in the remaining 57 cases. Barthel index scores of ADL were ≤40 (n = 1), 41–60 (n = 1), and >60 (n = 55); scores of 100 were obtained in 48 cases, with no dysfunctions. Conclusion. Satisfactory results can be achieved with minimally invasive surgery in treating acute epidural hematoma with hematoma volumes ranging from 13 to 145 mL. For patients with hematoma volume >50 mL and even cerebral herniation, flexible application of minimally invasive surgery would help improve treatment efficacy. PMID:27144170

  1. Treatment of Acute Promyelocytic Leukemia for Older Patients

    PubMed Central

    Prebet, Thomas; Gore, Steven D.

    2013-01-01

    Acute promyelocytic leukemia (APL) represents a remarkable disease in which leukemogenesis is driven by the PML-RARα oncogene and for which targeted treatment with all-trans retinoic acid (ATRA)–based therapy allows substantial chance of cure. APL is seen in a small subset of older patients, with age representing one of the most important prognostic factors for outcome of treatment. Unlike other acute leukemias, the inferior outcomes for APL in older patients relates less to changes in disease biology and more to increased toxicity of ATRA and chemotherapy combination regimens used to induce hematologic and molecular responses. Risk-adapted strategies that use less-toxic agents, such as arsenic trioxide, allow treatment of older patients, with greater efficiency and better chances of cure. PMID:21393443

  2. Intra-Arterial Treatment Methods in Acute Stroke Therapy

    PubMed Central

    Nguyen, Thanh N.; Babikian, Viken L.; Romero, Rafael; Pikula, Aleksandra; Kase, Carlos S.; Jovin, Tudor G.; Norbash, Alexander M.

    2011-01-01

    Acute revascularization is associated with improved outcomes in ischemic stroke patients. It is unclear which method of intra-arterial intervention, if any, is ideal. Promising approaches in acute stroke treatment are likely a combination of intravenous and endovascular revascularization efforts, combining early treatment initiation with direct clot manipulation and/or PTA/stenting. In this review, we will discuss available thrombolytic therapies and endovascular recanalization techniques, beginning with chemical thrombolytic agents, followed by mechanical devices, and a review of ongoing trials. Further randomized studies comparing medical therapy, intravenous and endovascular treatments are essential, and their implementation will require the wide support and enthusiasm from the neurologic, neuroradiologic, and neurosurgical stroke communities. PMID:21516256

  3. The acute and preventative treatment of episodic migraine

    PubMed Central

    Miller, Sarah

    2012-01-01

    Episodic migraine is a common debilitating condition with significant worldwide impact. An effective management plan must include acute treatment to relieve the pain and potential disability associated with the attacks and may also include preventative treatments with an aim of decreasing attack frequency and severity in the longer term. Acute treatments must be limited to a maximum of 2-3 days a week to prevent medication overuse headache and focus on simple analgesia, non-steroidal anti-inflammatory drugs and triptans. Preventative treatments are numerous and should be considered when migraine attacks are frequent and or disabling, acute medication is failing, in special circumstances such as hemiplegic migraines or if the patient requests them. All preventative medications must be given at therapeutic doses for at least 6-8 weeks before an adequate trial can be judged ineffective. The most important factor in choosing drugs is the patient and the clinical features of their attack and treatment should be tailored to these. Relative co-morbidities will influence drug choice, as will the side effect profile and the efficacy of the drug. First line preventative drugs include ß-blockers, amitriptyline and anti-epileptic drugs such as topiramate and valproate. Drugs with lower efficacy or poorer side effect profiles include selective serotonin reuptake inhibitors (SSRIs), calcium channel antagonists, gabapentin and herbal medicines. PMID:23024562

  4. 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

  5. Acute low back pain: diagnostics and treatment.

    PubMed

    Becker, F C

    2001-03-01

    How many times have you heard from a patient or groaned yourself "Oh, my aching back?" Innocuous movements such as reaching, stooping, or leaning are halted mid-performance as you sense "something" give, catch, snap, grab, or slide in your lower back. Such subjective complaints may also include sensations of discomfort described as stabbing, sharp, dull, hot/burning, tingling, or numbing. In practice, you will be required to assess these subjective symptoms, effectively document objective data, formulate a diagnosis, and plan appropriate treatment for your patients. Careful attention to history, associated symptoms, and following a systematic approach to back pain can make the rule-in/out differentials less taxing on both the practitioner and the patient. PMID:11329554

  6. Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review

    PubMed Central

    Carris, Nicholas W.; Pardo, Joe; Montero, Jose; Shaeer, Kristy M.

    2015-01-01

    Doxycycline, a commonly prescribed tetracycline, remains on intermittent shortage. We systematically reviewed the literature to assess minocycline as an alternative to doxycycline in select conditions, given doxycycline's continued shortage. We identified 19 studies, 10 of which were published before 2000. Thirteen of the studies were prospective, but only 1 of these studies was randomized. Based on the available data, we found minocycline to be a reasonable substitute for doxycycline in the following scenarios: skin and soft-tissue infections and outpatient treatment of community-acquired pneumonia in young, otherwise healthy patients or in patients with macrolide-resistant Mycoplasma pneumoniae, as well as Lyme disease prophylaxis and select rickettsial disease should doxycycline be unavailable. PMID:26719847

  7. [Tulozin in combined treatment of patients with acute urinary retention].

    PubMed

    Avdoshin, V P; Andriukhin, M I; Mikhaĭlikov, T G; Ol'shanskaia, E V; Khunov, A Z

    2009-01-01

    There is much evidence that tulozin promotes recovery of spontaneous urination, Qmax and is effective in combined treatment of patients with acute retention of urine caused by prostatic adenoma. Tulozin produces positive changes in the lower urinary tract symptoms. Rare occurrence of side effects enables long-term treatment and achievement of good therapeutic response. Tulozin is recommended for patients of younger age, with minimal comorbid pathology, hypotonic with orthostatic reactions, history of side effects in the treatment of other alpha-adrenoblockers, in comorbid hypertention, hypercholesterolemia, retrograde ejaculation, low potention, overactive bladder, prostatitis, after prostatic TUR, transvesical adenomectomy. PMID:19824378

  8. Minocycline Improves Functional Outcomes, Memory Deficits, and Histopathology after Endovascular Perforation-Induced Subarachnoid Hemorrhage in Rats

    PubMed Central

    Sherchan, Prativa; Lekic, Tim; Suzuki, Hidenori; Hasegawa, Yu; Rolland, William; Duris, Kamil; Zhan, Yan; Tang, Jiping

    2011-01-01

    Abstract Subarachnoid hemorrhage (SAH) results in significant long-lasting cognitive dysfunction. Therefore, evaluating acute and long-term outcomes after therapeutic intervention is important for clinical translation. The aim of this study was to use minocycline, a known neuroprotectant agent, to evaluate the long-term benefits in terms of neurobehavior and neuropathology after experimental SAH in rats, and to determine which neurobehavioral test would be effective for long-term evaluation. SAH was induced by endovascular perforation in adult male Sprague-Dawley rats (n=118). The animals were treated with intraperitoneal injection of minocycline (45 mg/kg or 135 mg/kg) or vehicle 1 h after SAH induction. In the short-term, animals were euthanized at 24 and 72 h for evaluation of neurobehavior, brain water content, and matrix metalloproteinase (MMP) activity. In the long-term, neurobehavior was evaluated at days 21–28 post-SAH, and histopathological analysis was done at day 28. High-dose but not low-dose minocycline reduced brain water content at 24 h, and therefore only the high-dose regimen was used for further evaluation, which reduced MMP-9 activity at 24 h. Further, high-dose minocycline improved spatial memory and attenuated neuronal loss in the hippocampus and cortex. The rotarod, T-maze, and water maze tests, but not the inclined plane test, detected neurobehavioral deficits in SAH rats at days 21–28. This study demonstrates that minocycline attenuates long-term functional and morphological outcomes after endovascular perforation-induced SAH. Long-term neurobehavioral assessments using the rotarod, T-maze, and water maze tests could be useful to evaluate the efficacy of therapeutic intervention after experimental SAH. PMID:22013966

  9. 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

  10. 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. PMID:25355373

  11. Rifaximin for the treatment of acute infectious diarrhea.

    PubMed

    Hong, Kyoung Sup; Kim, Joo Sung

    2011-07-01

    Rifaximin is a nonabsorbable rifamycin derivative with an excellent safety profile and a broad spectrum of antimicrobial activity against a variety of enteropathogens causing acute infectious diarrhea. After oral ingestion, its bioavailability is known to be less than 0.4%, and it has a low potential for significant drug interactions. In the treatment of travelers' diarrhea caused by noninvasive diarrheagenic Escherichia coli, it has been demonstrated that rifaximin significantly shortens the duration of diarrhea and has an efficacy similar to that of ciprofloxacin. Moreover, according to two randomized placebo-controlled trials, prophylactic treatment with rifaximin reduced the risk of developing travelers' diarrhea by more than 50% compared with the placebo group. For the treatment of acute diarrhea unrelated to travel, a short course of rifaximin significantly reduced the duration of diarrhea, and its overall efficacy was comparable to that of ciprofloxacin. The discrepancy between the in vitro and in vivoantimicrobial activities of rifaximin, however, and the clinical implication of the rapid appearance of bacterial resistance, must be further elucidated. In conclusion, this gut-selective antibiotic seems to be a promising option for the treatment of acute infectious diarrhea secondary to noninvasive E. coli and also appears to be effective in chemoprophylaxis for travelers' diarrhea. PMID:21765867

  12. Rifaximin for the treatment of acute infectious diarrhea

    PubMed Central

    Hong, Kyoung Sup; Kim, Joo Sung

    2011-01-01

    Rifaximin is a nonabsorbable rifamycin derivative with an excellent safety profile and a broad spectrum of antimicrobial activity against a variety of enteropathogens causing acute infectious diarrhea. After oral ingestion, its bioavailability is known to be less than 0.4%, and it has a low potential for significant drug interactions. In the treatment of travelers’ diarrhea caused by noninvasive diarrheagenic Escherichia coli, it has been demonstrated that rifaximin significantly shortens the duration of diarrhea and has an efficacy similar to that of ciprofloxacin. Moreover, according to two randomized placebo-controlled trials, prophylactic treatment with rifaximin reduced the risk of developing travelers’ diarrhea by more than 50% compared with the placebo group. For the treatment of acute diarrhea unrelated to travel, a short course of rifaximin significantly reduced the duration of diarrhea, and its overall efficacy was comparable to that of ciprofloxacin. The discrepancy between the in vitro and in vivoantimicrobial activities of rifaximin, however, and the clinical implication of the rapid appearance of bacterial resistance, must be further elucidated. In conclusion, this gut-selective antibiotic seems to be a promising option for the treatment of acute infectious diarrhea secondary to noninvasive E. coli and also appears to be effective in chemoprophylaxis for travelers’ diarrhea. PMID:21765867

  13. Minocycline with aspirin: an approach to attenuate diabetic nephropathy in rats.

    PubMed

    Kumar Bhatt, Lokesh; Addepalli, Veeranjaneyulu

    2011-01-01

    Degradation of extracellular matrix (ECM) by enhanced production of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in diabetes leads to nephropathy. Cyclooxygenases (COX) further increase levels of these MMPs. The objective of present study was to inhibit MMP-2 and MMP-9 by combination of minocycline and aspirin to treat diabetic nephropathy. Diabetes was induced in male Wistar rats by streptozotocin (STZ, 55 mg/kg i.p.). Four weeks after diabetes induction, the rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of 4 weeks. At the end of eighth week fluid input, urine output, and renal function tests were carried out for diagnosis of diabetic nephropathy. Renal hypertrophy was measured and histopathology was done to evaluate renal damage. Diabetes produced significant loss of body weight, polyuria, polydipsia, hyperglycemia, and increase in blood pressure. Serum creatinine, urea, and blood urea nitrogen levels were found to be increased significantly in the STZ group diabetic rats. Treatment with combination of minocycline and aspirin significantly prevented the rise in creatinine, urea, and blood urea nitrogen levels and increased creatinine clearance. Image analysis of kidneys revealed that collagen level was significantly decreased in combined treated group when compared with control. Results of present study suggest that MMP-2 and MMP-9 inhibition in presence of COX inhibitor prevents the development of experimental diabetic nephropathy in rats and can be a potential approach for the treatment. PMID:21219209

  14. Minocycline attenuates hypoxia-inducible factor-1α expression correlated with modulation of p53 and AKT/mTOR/p70S6K/4E-BP1 pathway in ovarian cancer: in vitro and in vivo studies

    PubMed Central

    Ataie-Kachoie, Parvin; Pourgholami, Mohammad H; Bahrami-B, Farnaz; Badar, Samina; Morris, David L

    2015-01-01

    Hypoxia-inducible factor (HIF)-1α is the key cellular survival protein under hypoxia, and is associated with tumor progression and angiogenesis. We have recently shown the inhibitory effects of minocycline on ovarian tumor growth correlated with attenuation of vascular endothelial growth factor (VEGF) and herein report a companion laboratory study to test if these effects were the result of HIF-1α inhibition. In vitro, human ovarian carcinoma cell lines (A2780, OVCAR-3 and SKOV-3) were utilized to examine the effect of minocycline on HIF-1 and its upstream pathway components to elucidate the underlying mechanism of action of minocycline. Mice harboring OVCAR-3 xenografts were treated with minocycline to assess the in vivo efficacy of minocycline in the context of HIF-1. Minocycline negatively regulated HIF-1α protein levels in a concentration-dependent manner and induced its degradation by a mechanism that is independent of prolyl-hydroxylation. The inhibition of HIF-1α was found to be associated with up-regulation of endogenous p53, a tumor suppressor with confirmed role in HIF-1α degradation. Further studies demonstrated that the effect of minocycline was not restricted to proteasomal degradation and that it also caused down-regulation of HIF-1α translation by suppressing the AKT/mTOR/p70S6K/4E-BP1 signaling pathway. Minocycline treatment of mice bearing established ovarian tumors, led to suppression of HIF-1α accompanied by up-regulation of p53 protein levels and inactivation of AKT/mTOR/p70S6K/4E-BP1 pathway. These data reveal the therapeutic potential of minocycline in ovarian cancer as an agent that targets the pro-oncogenic factor HIF-1α through multiple mechanisms. PMID:25973298

  15. Idiopathic thrombocytopenic purpura following successful treatment of acute lymphoblastic leukemia.

    PubMed

    Tannir, N M; Kantarjian, H

    2001-03-01

    Thrombocytopenia is common in patients with acute lymphocytic leukemia (ALL) at diagnosis. It is a universal side effect of dose-intensive regimens employed in the treatment of adult ALL. In patients with ALL who achieve remission, thrombocytopenia frequently indicates relapse. We report three adult patients successfully treated for ALL who developed thrombocytopenia and were found to have immune-mediated thrombocytopenia (ITP). Possible pathophysiologic mechanisms underlying the association of ALL and ITP are discussed. PMID:11342378

  16. Acute pancreatitis as a complication of childhood cancer treatment.

    PubMed

    Stefanović, Milica; Jazbec, Janez; Lindgren, Fredrik; Bulajić, Milutin; Löhr, Matthias

    2016-05-01

    Acute pancreatitis (AP) is now well recognized as a possible complication of childhood cancer treatment, interrupting the chemotherapy regimen, and requiring prolonged hospitalization, possibly with intensive care and surgical intervention, thereby compromising the effect of chemotherapy and the remission of the underlying malignant disease. This review summarizes the current literature and presents the various etiological factors for AP during chemotherapy as well as modern trends in the diagnosis and therapy of AP in children. PMID:26872431

  17. Acute and long-term treatment of mania.

    PubMed

    Vieta, Eduard; Sanchez-Moreno, Jose

    2008-01-01

    The treatment of mania starts with a correct diagnosis and elementary measures to prevent risks for the patient, relatives, and others. Sometimes, compulsory admission and treatment may be required for a few days. Patients with psychotic or mixed mania may be more difficult to treat. At the present time, there is solid evidence supporting the use of lithium, the anticonvulsants valproate and carbamazepine, and the antipsychotics chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment-refractory cases. However, in clinical practice, combination therapy is the rule rather than the exception. The treatment of acute mania deserves a long-term view, and the evidence base for some treatments may be stronger than for others. When taking decisions about treatment, tolerability should also be a major concern, as differences in safety and tolerability may exceed differences in efficacy for most compounds. Psychoeducation of patients and caregivers is a powerful tool that should be used in combination with medication for optimal long-term outcome. Functional recovery should be the ultimate goal. PMID:18689287

  18. 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

  19. Acute diverticulitis. Comparison of treatment in immunocompromised and nonimmunocompromised patients.

    PubMed

    Perkins, J D; Shield, C F; Chang, F C; Farha, G J

    1984-12-01

    The clinical course and required treatment of diverticulitis were reviewed in 76 nonimmunocompromised patients and 10 immunocompromised patients. The immunocompromised patients presented with either minimal or no symptoms and findings. Therefore, to make the diagnosis of acute diverticulitis in this group, a high index of suspicion must be maintained. The required treatment varied considerably between the two groups. In 45 nonimmunocompromised patients (76 percent), medical therapy was successful. Medical treatment failed in the other 14 patients (24 percent). However, the compromised group had no patients in whom medical therapy was successful (100 percent failure rate). Thirty-one of the nonimmunocompromised patients (41 percent) required an operation, whereas 100 percent of the immunocompromised patients with acute diverticulitis required an operation. By relating postoperative complications, we were unable to determine the initial operative procedure of choice in the nonimmunocompromised group; however, in the immunocompromised group, colostomy and resection had fewer surgical complications than colostomy and drainage. The immunocompromised patient with acute diverticulitis requires operation. We believe the operation of choice is colostomy and resection of the involved segment. PMID:6507744

  20. Oral almotriptan: practical uses in the acute treatment of migraine.

    PubMed

    Dowson, Andrew J

    2004-05-01

    Almotriptan (Almogran, Lundbeck; Almirall Prodesfarma; Axert, Ortho-McNeil) is a novel 5-HT(1B/1D) receptor agonist (triptan) that is widely available on prescription for the acute treatment of migraine. Almotriptan has pharmacodynamic and pharmacokinetic profiles that make it suitable for use in this indication. It is a potent agonist at 5-HT(1B), (1D) and (1F) receptors, while having a low affinity for other 5-HT receptors. It is also a potent inhibitor of neurogenic inflammation. Almotriptan has a high oral bioavailability, is absorbed rapidly, has a relatively short plasma half-life and its route of elimination presents few potential problems. Placebo-controlled dose-finding studies have demonstrated that almotriptan tablets are effective and well-tolerated in the acute treatment of migraine, with a 12.5 mg dose providing the best balance between efficacy and tolerability. Large placebo-controlled studies show that the efficacy of oral almotriptan is comparable with that of the other oral triptans. In direct comparator-controlled studies, almotriptan was as effective as sumatriptan 50 and 100 mg but had a superior tolerability profile. Furthermore, the efficacy and tolerability of almotriptan is sustained in the long term following open-label administration. Meta-analyses and post hoc analyses of clinical data confirm these findings. In conclusion, almotriptan 12.5 mg is a good therapeutic choice for the symptomatic treatment of acute migraine attacks. PMID:15853532

  1. Minocycline provides protection against beta-amyloid(25-35)-induced alterations of the somatostatin signaling pathway in the rat temporal cortex.

    PubMed

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

    2008-07-17

    Minocycline is a semi-synthetic second-generation tetracycline known to improve cognition in amyloid precursor protein transgenic mice. Whether it can protect the somatostatin (SRIF) receptor-effector system, also involved in learning and memory, from alterations induced by chronic i.c.v. infusion of beta-amyloid peptide (Abeta)(25-35) is presently unknown. Hence, in the present study, we tested the effects of minocycline on the SRIF signaling pathway in the rat temporal cortex. To this end, male Wistar rats were injected with minocycline (45 mg/kg body weight) i.p. twice on the first day of treatment. On the following day and during 14 days, Abeta(25-35) was administered i.c.v. via an osmotic minipump connected to a cannula implanted in the left lateral ventricle (300 pmol/day). Minocycline (22.5 mg/kg, i.p.) was injected once again the last 2 days of the Abeta(25-35) infusion. The animals were killed by decapitation 24 h after the last drug injection. Our results show that minocycline prevents the decrease in SRIF receptor density and somatostatin receptor (sst) 2 expression and the attenuated capacity of SRIF to inhibit adenylyl cyclase (AC) activity, alterations present in the temporal cortex of Abeta(25-35)-treated rats. Furthermore, minocycline blocks the Abeta(25-35)-induced decrease in phosphorylated cyclic AMP (cAMP) response element binding protein (p-CREB) content and G-protein-coupled receptor kinase 2 (GRK) protein expression in this brain area. Altogether, the present data demonstrate that minocycline in vivo provides protection against Abeta-induced impairment of the SRIF signal transduction pathway in the rat temporal cortex and suggest that it may have a potential as a therapeutic agent in human Alzheimer's disease, although further studies are warranted. PMID:18555616

  2. Minocycline prevents morphine-induced apoptosis in rat cerebral cortex and lumbar spinal cord: a possible mechanism for attenuating morphine tolerance.

    PubMed

    Hassanzadeh, Kambiz; Habibi-asl, Bohlool; Farajnia, Safar; Roshangar, Leila

    2011-05-01

    Tolerance to the chronic administration of opioids such as morphine reduces the utility of these drugs in pain management. Despite significant investigation, the precise cellular mechanisms underlying opioid tolerance and dependence remain elusive. It has been indicated that tolerance to the analgesic effect of morphine is associated with apoptosis in the central nervous system. The aim of this study was to examine the effects of the intracerebroventricular (icv) administration of minocycline (a second-generation tetracycline) on morphine-induced apoptosis in the cerebral cortex and lumbar spinal cord of rats after morphine-induced tolerance. Different groups of rats received either morphine (ip) and distilled water (icv) or morphine and different doses of minocycline (icv) or minocycline alone once per day. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to analyze apoptosis. The anti-apoptotic factors, Bcl-2 and HSP 70 and the pro-apoptotic element caspase-3 were evaluated by immunoblotting. The results indicated that minocycline attenuated the number of apoptotic cells in both the cerebral cortex and lumbar spinal cord. Immunoblotting findings showed that the amounts of anti-apoptotic agents (Bcl-2 and HSP 70) were greater in the treatment groups than in the controls in both regions. Although minocycline did not change the level of caspase-3 at the doses used with morphine but the minocycline treated rats showed a significantly lower increase in caspase-3 activity than did in the control. In conclusion, minocycline decreased the number of TUNEL-positive cells and increased the amount of anti-apoptotic factors (Bcl-2 and HSP 70), but did not change the caspase-3 content. PMID:20711699

  3. Comparison of the Effect of Minocycline and Simvastatin on Functional Recovery and Gene Expression in a Rat Traumatic Brain Injury Model

    PubMed Central

    Vonder Haar, Cole; Elmore, Brandy E.; Moore, Lynn H.; Wright, Amanda M.; Kantor, Eric D.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Hoane, Michael R.

    2014-01-01

    Abstract The goal of this study was to compare the effects of minocycline and simvastatin on functional recovery and brain gene expression after a cortical contusion impact (CCI) injury. Dosage regimens were designed to provide serum concentrations in a rat model in the range obtained with clinically approved doses; minocycline 60 mg/kg q12h and simvastatin 10 mg/kg q12h for 72 h. Functional recovery was assessed using motor and spatial learning tasks and neuropathological measurements. Microarray-based transcriptional profiling was used to determine the effect on gene expression at 24 h, 72 h, and 7 days post-CCI. Gene Ontology analysis (GOA) was used to evaluate the effect on relevant biological pathways. Both minocycline and simvastatin improved fine motor function, but not gross motor or cognitive function. Minocycline modestly decreased lesion size with no effect of simvastatin. At 24 h post-CCI, GOA identified a significant effect of minocycline on chemotaxis, blood circulation, immune response, and cell to cell signaling pathways. Inflammatory pathways were affected by minocycline only at the 72 h time point. There was a minimal effect of simvastatin on gene expression 24 h after injury, with increasing effects at 72 h and 7 days. GOA identified a significant effect of simvastatin on inflammatory response at 72 h and 7 days. In conclusion, treatment with minocycline and simvastatin resulted in significant effects on gene expression in the brain reflecting adequate brain penetration without producing significant neurorestorative effects. PMID:24308531

  4. Safe intravenous thrombolysis in acute stroke despite treatment with rivaroxaban.

    PubMed

    Bornkamm, Katharina; Harloff, Andreas

    2014-11-01

    Data regarding intravenous thrombolysis in stroke patients receiving new oral anticoagulant drugs (nOAC) is sparse. In the near future, however, an increasing number of patients with atrial fibrillation will suffer recurrent stroke despite treatment with nOAC. This will cause a significant therapeutic dilemma as thrombolysis is contraindicated under such circumstances. We describe an 81-year-old patient presenting with acute ischemic stroke who was successfully treated with intravenous thrombolysis despite ongoing treatment with rivaroxaban. Our case report indicates that thrombolysis under nOAC may be safe under certain conditions and emphasizes the importance of establishing and performing specific anticoagulation tests for nOAC. PMID:24938385

  5. 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. PMID:26488033

  6. Treatment of Neuromyelitis Optica Spectrum Disorder: Acute, Preventive, and Symptomatic

    PubMed Central

    Kessler, Remi A.; Mealy, Maureen A.; Levy, Michael

    2016-01-01

    Opinion statement Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that primarily attacks the optic nerves and spinal cord leading to blindness and paralysis. The spectrum of the disease has expanded based on the specificity of the autoimmune response to the aquaporin-4 water channel on astrocytes. With wider recognition of NMOSD, a standard of care for treatment of this condition has condition based on a growing series of retrospective and prospective studies. This review covers the present state of the field in the treatment of acute relapses, preventive approaches, and therapies for symptoms of NMOSD. PMID:26705758

  7. Is Minocycline an Antiviral Agent? A Review of Current Literature.

    PubMed

    Nagarakanti, Sandhya; Bishburg, Eliahu

    2016-01-01

    Minocycline is a second-generation semi-synthetic derivative of tetracycline and has well-known anti-bacterial effects. The drug possesses anti-inflammatory, anti-oxidant, anti-apoptotic and immunomodulatory effects. The drug is widely used in bacterial infections and non-infectious conditions such as acne, dermatitis, periodontitis and neurodegenerative conditions. Minocycline was shown to have antiviral activity in vitro and also against different viruses in some animal models. Some studies have been done on human patients infected with Human Immunodeficiency Virus. We have review the available data regarding minocycline activity as an antiviral agent. PMID:26177421

  8. Minocycline potentiates the anti-hyperalgesic effect of ceftriaxone in CCI-induced neuropathic pain in rats

    PubMed Central

    Amin, B.; Hajhashemi, V.; Hosseinzadeh, H.

    2015-01-01

    Glutamate neurotoxicity and pro-inflammatory cytokines have an important role in the central sensitization of neuropathic pain. The purpose of the present study was to evaluate anti-hyperalgesic effect of repeated administration of ceftriaxone, which selectively activates and increases the expression of glutamate transporter, as well as minocycline, a selective inhibitor of microglia activation, either alone or together in Wistar rats subjected to the chronic constriction injury (CCI) of sciatic nerve. Ceftriaxone (100, 150 and 200 mg/kg) and minocycline (25, 50 and 100 mg/kg) were administered intraperitoneally from the day of surgery for seven consecutive days. Thermal hyperalgesia was assessed by focal radiant heat source on the hind paw of animals one day before surgery and on 3, 5, 7, 10 and 14 days following that. Ceftriaxone dose dependently, attenuated thermal hyperalgesia in animals. None of the administered doses of minocycline affected the CCI induced-thermal hyperalgesia in neuropathic animals. A fixed dose of minocycline (50 mg/kg) combined with three different doses of ceftriaxone administered for 7 consecutive days yielded a potentiating effect in the enhancing latency time to noxious thermal stimulus remaining until the 14th day post-surgery. The results suggest that modulation of microglia activity could have a supportive role in the improvement of CCI-induced thermal hyperalgesia and combination of such classes of drugs which have no antibiotic effects could be a new and promising therapeutic strategy for treatment. PMID:26430455

  9. Vasodilator treatment for acute and chronic heart failure.

    PubMed Central

    Chatterjee, K; Parmley, W W

    1977-01-01

    The current status of the use of vasodilator drugs in the treatment of acute and chronic heart failure has been reviewed. It is apparent that vasodilator treatment can be used effectively in some patients with heart failure with a beneficial haemodynamics response, and that vasodilator agents are likely to find an important place in the management of such patients. Vasodilator treatment may be associated with complications and must be used with care. Though several nonparenteral vasodilator agents have been investigated, no ideal drug is yet available for the treatment of chronic heart failure. Nevertheless, it is probable that suitable drugs will emerge and find an important place in the management of such patients. Images PMID:884021

  10. Treatment of Orbital Complications Following Acute Rhinosinusitis in Children

    PubMed Central

    Wan, Yuzhu; Shi, Guanggang; Wang, Haibo

    2016-01-01

    Background: The orbital complications account for about 80% of all complications secondary to acute rhinosinusitis. If the treatment is not correct and in time, orbital complications could progress rapidly, leading to optic neuritis, cavernous sinus thrombophlebitis or life-threatening intracranial complications. Aims: To evaluate the therapeutic efficacy of conservative therapy for the patients with orbital cellulitis and endoscopic sinus surgery (ESS) performed on patients with subperiosteal abscess (SPA) secondary to acute rhinosinusitis in children. Study Design: Retrospective cross-sectional study. Methods: The retrospective study included 31 pediatric patients with orbital complications secondary to acute rhinosinusitis. In all cases, intensive treatment was initiated with a combination of oral or intravenous antibiotics, glucocorticoid and gelomyrtol forte after admission. ESS was performed if an improvement in the condition of patients did not occur after 48 hours. However, the patients with orbital SPA, motility disorders of eyeball or decreased vision received ESS immediately within 24 hours. Results: Sixteen patients were cured by conservative therapy and 15 patients by ESS. All of the signs and symptoms disappeared after conservative therapy or ESS. There were no recurrences within the follow-up period of 1 to 8 years. Conclusion: Conservative therapy is an effective method for patients with inflammatory edema and most cases of orbital cellulitis in children. SPA can be cured by ESS. PMID:27606135

  11. Treatment of acute limb ischemia with focus on endovascular techniques.

    PubMed

    Zeller, T; Tepe, G

    2009-05-01

    Acute limb ischemia is still the most frequent cause of major limb loss. Timely and fast revascularization is the key for limb salvage and patient survival. Large randomized trials showed equivalency of surgical and endovascular revascularization by means of local lysis with urokinase (TOPAS, STILE). New lytic agents and their modified application such as via a pulse spray catheter or combined with an ultrasound catheter and the combination with glycoprotein IIb/IIIa receptor antagonists have increased the efficacy and speed of thrombolysis. Recently, mechanical thrombectomy devices have become more widespread because intervention time and bleeding complications can be reduced. This review article summarizes the clinical presentation of and the treatment options for acute arterial occlusive disease caused either by embolism or local thrombosis. PMID:19588300

  12. Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury.

    PubMed

    Papa, Simonetta; Caron, Ilaria; Erba, Eugenio; Panini, Nicolò; De Paola, Massimiliano; Mariani, Alessandro; Colombo, Claudio; Ferrari, Raffaele; Pozzer, Diego; Zanier, Elisa R; Pischiutta, Francesca; Lucchetti, Jacopo; Bassi, Andrea; Valentini, Gianluca; Simonutti, Giulio; Rossi, Filippo; Moscatelli, Davide; Forloni, Gianluigi; Veglianese, Pietro

    2016-01-01

    Many efforts have been performed in order to understand the role of recruited macrophages in the progression of spinal cord injury (SCI). Different studies revealed a pleiotropic effect played by these cells associated to distinct phenotypes (M1 and M2), showing a predictable spatial and temporal distribution in the injured site after SCI. Differently, the role of activated microglia in injury progression has been poorly investigated, mainly because of the challenges to target and selectively modulate them in situ. A delivery nanovector tool (poly-ε-caprolactone-based nanoparticles) able to selectively treat/target microglia has been developed and used here to clarify the temporal and spatial involvement of the pro-inflammatory response associated to microglial cells in SCI. We show that a treatment with nanoparticles loaded with minocycline, the latter a well-known anti-inflammatory drug, when administered acutely in a SCI mouse model is able to efficiently modulate the resident microglial cells reducing the pro-inflammatory response, maintaining a pro-regenerative milieu and ameliorating the behavioral outcome up to 63 days post injury. Furthermore, by using this selective delivery tool we demonstrate a mechanistic link between early microglia activation and M1 macrophages recruitment to the injured site via CCL2 chemokine, revealing a detrimental contribution of pro-inflammatory macrophages to injury progression after SCI. PMID:26474039

  13. [Treatment of acute myocardial infarction--an elucidative report].

    PubMed

    Madsen, E B; Godtfredsen, J; Hansen, J F; Jensen, G; Nielsen, B L; Nielsen, P E; Nielsen, T T; Pedersen, A; Rømer, F; Sandøe, E

    1989-06-01

    The present-day optimal treatment of patients with acute myocardial infarction (AMI) is reviewed. The prehospital phase should be as brief as possible. Emergency observation and treatment in hospital should be initiated without delay. Schematic stages for mobilization have been discarded and free mobilization is recommended. Routine acute intervention with thrombolysis is recommended for patients in whom symptoms have been present for 6-12 hours and treatment with Aspirin is recommended. Beta-blocking agents are recommended for patients with increased risk after discharge. Treatment of ventricular and supraventricular arrhythmias, block and cardiac failure are reviewed in detail. Patients without complications should be monitored for three to five days and may be discharged after seven to ten days. Exercise ECG should be carried out at discharge to assess the working capacity, ischaemia and subjective reaction. The importance of good patient information is emphasized. Cessation of smoking, control of lipids and blood pressure are important as secondary interventions. As far as possible, outpatient control should be offered after discharge. The criteria for referral to specialized cardiological departments are established both for emergency and elective referral. Patients under the age of 70 years with high risk for repeated AMI or death after discharge (with residual ischaemia) should possibly be referred for coronary arteriography. PMID:2567543

  14. Magnetic resonance imaging in acute ischemic stroke treatment.

    PubMed

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven; Kang, Dong-Wha

    2014-09-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872

  15. Magnetic Resonance Imaging in Acute Ischemic Stroke Treatment

    PubMed Central

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven

    2014-01-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872

  16. Comparative Susceptibility of Anaerobic Bacteria to Minocycline, Doxycycline, and Tetracycline

    PubMed Central

    Chow, Anthony W.; Patten, Valerie; Guze, Lucien B.

    1975-01-01

    The comparative susceptibility of 622 recent clinical isolates of anaerobic bacteria to minocycline, doxycycline, and tetracycline was determined by an agar-dilution technique. In addition to Bacteroides fragilis, a variety of other anaerobic bacteria was resistant to achievable blood concentrations of tetracycline (55% inhibited by 6.25 μg/ml) and doxycycline (58% inhibited by 2.5 μg/ml). In contrast, minocycline was significantly more active (P < 0.05) than both doxycycline and tetracycline, and 70% of strains were inhibited by achievable blood concentrations of this antibiotic (2.5 μg/ml). The enhanced activity of minocycline was particularly striking for Peptococcus asaccharolyticus, P. magnus, P. prevotii, Peptostreptococcus anaerobius, and Bacteroides melaninogenicus. Further evaluation of the clinical efficacy of minocycline against anaerobic infections is indicated. PMID:1137358

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

    PubMed

    Sharma, Raman; Al Jayoussi, Ghaith; 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

  18. 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

  19. Economic evaluation of treatment for acute lymphoblastic leukaemia in childhood.

    PubMed

    Rae, C; Furlong, W; Jankovic, M; Moghrabi, Albert; Naqvi, A; Sala, A; Samson, Y; DePauw, S; Feeny, D; Barr, R

    2014-11-01

    Berlin-Frankfurt-Munster (BFM) and Dana-Farber Cancer Institute (DFCI) consortia's treatment strategies for acute lymphoblastic leukaemia (ALL) in children are widely used. We compared the health effects and monetary costs of hospital treatments for these two strategies. Parents of children treated at seven centres in Canada, Italy and the USA completed health-related quality of life (HRQL) assessments during four active treatment phases and at 2 years after treatment. Mean HRQL scores were used to calculate quality-adjusted life years (QALYs) for a period of 5 years following diagnosis. Total costs of treatment were determined from variables in administrative databases in a universally accessible and publicly funded healthcare system. Valid HRQL assessments (n = 1200) were collected for 307 BFM and 317 DFCI patients, with costs measured for 66 BFM and 28 DFCI patients. QALYs per patient were <1.0% greater for BFM than DFCI. Median HRQL scores revealed no difference in QALYs. The difference in mean total costs for BFM (US$88 480) and DFCI (US$93 026) was not significant (P = 0.600). This study provides no evidence of superiority for one treatment strategy over the other. Current BFM or DFCI strategies should represent conventional management for the next economic evaluation of treatments for ALL in childhood. PMID:24393150

  20. Acute treatment of migraine and the role of triptans.

    PubMed

    Freitag, F G

    2001-03-01

    The use of triptans has improved the ability to treat migraine successfully compared with older treatments. Speed of relief, consistency of effect, and good tolerability have been the hallmarks of these agents. All of the currently available triptans have comparable efficacy and tolerability. Variables between the agents may lead to one agent or dose form being preferred over another in various clinical scenarios. The triptans that are forthcoming may improve on these options through enhanced efficacy rates, tolerability, and headache recurrence rates. There exist increasing options for migraine treatment that may further improve the clinical effects of the older and newer triptans through early treatment of migraine at the stages of mild migraine pain, or even during the prodromal phase of the attack. Additionally, recent work suggests that mini-prophylaxis of migraine at the menses is a highly successful treatment option with the triptans. In this age of managed care, providing cost-effective treatment of headache will take on increasing importance. Techniques such as stratification of acute treatments may enhance cost-effective care, whereas ready availability of the triptans may lead to significant improvements in utilization of parameters such as office visits, emergency room treatment, and even hospitalization. PMID:11898508

  1. Prospects for the temporary treatment of acute liver failure.

    PubMed

    Stockmann, Hein B A C; IJzermans, Jan N M

    2002-02-01

    At present, the most successful treatment of acute liver failure is orthotopic liver transplantation, with survival rates ranging from 70% to 85%. However, mortality rates for liver failure remain high because of the shortage of available donor organs. Therefore, there has been renewed interest in temporary treatment methods for patients with acute liver failure to either allow liver regeneration or await liver transplantation. It is thought that the function of the liver can only be replaced with the biological substrate, e.g. liver cells or a whole liver specimen, which requires the availability of liver tissue from xenogeneic or human sources. In this review, existing temporary liver support techniques are summarized and the potential hazards are described. These include the immunological implications of these techniques, e.g. the host versus graft reaction, which may influence the effectivity of the support system, and in the long run may sensitize the patient to subsequent allogeneic transplantation. The graft versus host reaction is also considered. At present, one of the major concerns is the threat of pig-to-human transmission of activated endogenous retrovirus present in the pig genome. An overview is given of literature concerning the transmission of retrovirus particles in vitro and in vivo. Finally, new solutions for the development of ex vivo systems for temporary treatment of patients with acute liver failure are discussed. These include the use of new immortalized human cell lines and human fetal hepatocytes, and the possibility of isolating, expanding and genetically manipulating stem cells in order to have stable differentiated and committed cells. PMID:11981346

  2. WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis.

    PubMed

    Di Saverio, Salomone; Birindelli, Arianna; Kelly, Micheal D; Catena, Fausto; Weber, Dieter G; Sartelli, Massimo; Sugrue, Michael; De Moya, Mark; Gomes, Carlos Augusto; Bhangu, Aneel; Agresta, Ferdinando; Moore, Ernest E; Soreide, Kjetil; Griffiths, Ewen; De Castro, Steve; Kashuk, Jeffry; Kluger, Yoram; Leppaniemi, Ari; Ansaloni, Luca; Andersson, Manne; Coccolini, Federico; Coimbra, Raul; Gurusamy, Kurinchi S; Campanile, Fabio Cesare; Biffl, Walter; Chiara, Osvaldo; Moore, Fred; Peitzman, Andrew B; Fraga, Gustavo P; Costa, David; Maier, Ronald V; Rizoli, Sandro; Balogh, Zsolt J; Bendinelli, Cino; Cirocchi, Roberto; Tonini, Valeria; Piccinini, Alice; Tugnoli, Gregorio; Jovine, Elio; Persiani, Roberto; Biondi, Antonio; Scalea, Thomas; Stahel, Philip; Ivatury, Rao; Velmahos, George; Andersson, Roland

    2016-01-01

    Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics. PMID:27437029

  3. Treatment of acute thoracic aortic syndromes using endovascular techniques

    PubMed Central

    Uğuz, Emrah; Canyiğit, Murat; Hıdıroğlu, Mete; Şener, Erol

    2016-01-01

    PURPOSE Acute thoracic aortic syndrome (ATAS) is a novel term to define emergency aortic conditions with common clinical features and challenges. Traditional management of ATAS includes surgical replacement of the aorta and is correlated with high perioperative mortality and morbidity. We aimed to evaluate our experience and outcomes in patients presenting with ATAS, managed by endovascular techniques. METHODS This cohort consisted of 31 consecutive patients (24 males; mean age, 57.5±13.81 years; range, 19–84 years) with acute thoracic aortic pathologies who underwent endovascular repair between January 2011 and January 2015. The study was designed as a retrospective analysis of prospectively maintained data. RESULTS Complicated acute type-B aortic dissection was the most common pathology (35.5%). All aortic stent-grafts (n=37) and dissection stents (n=9) were implanted with 100% procedural success. The overall in-hospital mortality was 9.7%. The mean follow-up duration of patients who were alive at 30 days was 25.9±11.49 months (3–53 months). So far, there have been no late deaths after 30 days. CONCLUSION In the high-risk setting of ATAS, endovascular procedures come forward as novel therapeutic strategies with promising results. Endovascular repair of ATAS can be considered as a first-line treatment alternative under emergency conditions with encouraging results, particularly when conventional surgical repair cannot be implemented due to prohibitive comorbidities. PMID:27113420

  4. 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

  5. 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. PMID:22335313

  6. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes

    PubMed Central

    Graham, Garth

    2016-01-01

    In the USA and internationally, women experience farranging differences with respect to acute coronary syndrome (ACS) and myocardial infarction (MI). Women suffer from more comorbidities than men, such as smoking, obesity, hypertension, diabetes, and poor mental health. They some-times exhibit atypical MI presentation symptoms and are overall less likely to present with chest pain. Women are more likely than men to encounter delays between the onset of symptoms and arrival at the hospital or to guideline treatment. The use of various surgical and pharmacological treatments, including revascularization approaches, also differs. Women, on average, have worse outcomes than men following MI, with more complications, higher mortality rates, and poorer recovery. Internationally, outcomes are similar despite various differences in health care and culture in non-US countries. In this review, we detail differences regarding ACS and MI in women, describing their complex correlations and discussing their possible causes. Educational approaches that are tailored to women might help to reduce the incidence of ACS and MI, as well as outcomes following hospitalization. Although outcomes following acute MI have been improving over the years, women may require special consideration in order to see continued improvement. PMID:26884685

  7. Pharmacological treatment of acute migraine in adolescents and children.

    PubMed

    Wöber-Bingöl, Çiçek

    2013-06-01

    Migraine is a common disease in children and adolescents. The incidence of migraine has increased alarmingly in the general population during recent decades. Migraine causes considerable individual suffering and impaired quality of life. Therefore, appropriate management is essential. In this article, the treatment of acute migraine in children and adolescents will be reviewed. Only a few randomized controlled studies have been published and high placebo rates are a major problem for proving superiority of active drugs. Generally, acetaminophen (paracetamol) and ibuprofen are accepted as drugs of first choice, even though the evidence is poor for the former and limited for latter. Among 14 studies on triptans in adolescents, 9 showed some superiority over placebo with respect to pain relief and pain freedom, and among 6 studies in children, 5 suggest some superiority over placebo. Sumatriptan nasal spray and zolmitriptan nasal spray have been approved for adolescents in Europe; almotriptan has been approved for adolescents in the USA, as has rizatriptan for patients aged 6-17 years. A recent study demonstrated the efficacy of a fixed combination of sumatriptan and naproxen in adolescents with migraine. In conclusion, evidence for the pharmacological treatment of acute migraine in children is very poor and evidence for adolescents is better but still limited. PMID:23575981

  8. An update of current treatments for adult acute myeloid leukemia

    PubMed Central

    Gardin, Claude

    2016-01-01

    Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose intensification and safer allogeneic HSCT procedures, allowing a larger proportion of patients to achieve durable remission. In addition, improved identification of patients at relatively low risk of relapse should limit their undue exposure to the risks of HSCT in first remission. The role of new effective agents, such as purine analogs or gemtuzumab ozogamicin, is still under investigation, whereas promising new targeted agents are under clinical development. In contrast, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. The availability of hypomethylating agents likely represents an encouraging first step for this latter population, and it is hoped will allow for more efficient combinations with novel agents. PMID:26660429

  9. Antibody-based treatment of acute myeloid leukaemia.

    PubMed

    Mulford, Deborah A; Jurcic, Joseph G

    2004-01-01

    Monoclonal antibodies have become an important treatment modality in cancer therapy. Genetically engineered chimaeric and humanised antibodies have demonstrated activity against a variety of tumours. Whereas the humanised anti-CD33 monoclonal antibody HuM195 has only modest activity against overt acute myeloid leukaemia (AML), it can eliminate minimal residual disease detectable by reverse transcription-polymerase chain reaction in acute promyelocytic leukaemia. High-dose radioimmunotherapy with beta-particle-emitting isotopes targeting CD33, CD45 and CD66 can potentially allow intensification of antileukaemic therapy before bone marrow transplantation. Conversely, alpha-particle immunotherapy with isotopes such as bismuth-213 or actinium-225 offers the possibility of selective tumour cell kill while sparing surrounding normal cells. Targeted chemotherapy with the anti-CD33-calicheamicin construct gemtuzumab ozogamicin has produced remissions as a single agent in patients with relapsed AML and appears promising when used in combination with standard chemotherapy in the treatment of newly diagnosed AML. PMID:14680472

  10. Clonazepam oral droplets for the treatment of acute epileptic seizures.

    PubMed

    Sakata, Osamu; Onishi, Hiraku; Machida, Yoshiharu

    2008-12-01

    Oral droplet formulations of clonazepam (CZ) were developed to examine their potentials as an alternative to i.v. administration for the treatment of acute epileptic seizures. Propylene glycol containing 2.5% (wt/wt) CZ with or without 5.0% (wt/wt) oleic acid (OA) was prepared as a solution by heating at 90 degrees C and subsequently lowering the temperature to 30 degrees C. The droplet (20 microL) was administered to the oral cavity between the lower gum and bottom lip before CZ precipitation started. With a droplet of propylene glycol loaded with 2.5% (wt/wt) CZ and 5.0% (wt/wt) OA, the plasma concentration reached 20 ng/mL (minimal effective concentration) within 10 min and was maintained between 20 and 60 ng/mL, less than a toxic level, for a period of 60 min. For a droplet of propylene glycol loaded only with CZ at 2.5% (wt/wt), it took more than 15 min for the plasma concentration to reach 20 ng/mL. It is suggested that a droplet of CZ/OA/propylene glycol (2.5:5.0:92.5, wt/wt) might be useful as an alternative to i.v. injection of CZ for the treatment of acute epileptic seizures. PMID:18720141

  11. Prognosis and treatment of patients with acute alcoholic hepatitis.

    PubMed

    Papastergiou, Vassilios; Burroughs, Andrew K; Tsochatzis, Emmanuel A

    2014-07-01

    Despite alcoholic hepatitis (AH) is the most acute manifestation of alcohol-related liver disease, its treatment remains controversial. Corticosteroids, given either as monotherapy or together with N-acetylecysteine, have been associated with a moderate short-term survival benefit in patients with severe disease. The Maddrey's discriminant function; Glasgow alcoholic hepatitis score; age, bilirubin, INR and creatinine score; and the Model for end-stage liver disease have been proposed for stratifying prognosis in AH enabling selection of the patients to treat. Definition of treatment non-responders using the Lille model after 7 days of therapy may prevent a detrimental impact of prolonged corticosteroids. Pentoxifylline is an effective alternative reducing the occurrence of hepatorenal syndrome. Emerging evidence supports use of liver transplantation in a strictly selected subset of corticosteroid non-responders. PMID:24716632

  12. [RESULTS OF AN ACUTE THROMBOSIS OF HEMORRHOIDAL NODES TREATMENT].

    PubMed

    Akhmedova, E V

    2015-09-01

    The results of treatment of 182 patients, suffering an acute thrombosis of hemorrhoidal nodes of various severity, were studied. In 93 (51.1%) patients (main group) an active surgical tactics was applied. There were conducted urgent, early and postponed operations. In 89 (48.9%) patients (control group) a conservative-expectant tactic was applied. The patients were operated on in terms of 9 - 10 days after admission to hospital. The terms of operation and the method of hemorrhoidectomy were choosed without taking into account the disease severity. Complications in the main group have occurred in 27 (29%) patients, their stationary treatment have lasted 7 - 11 days. In a control group complications were revealed in 27 (30.3%) patients, their stationary stay have lasted from 9 to 28 days. PMID:26817088

  13. Acute methyl salicylate toxicity complicating herbal skin treatment for psoriasis.

    PubMed

    Bell, Anthony J; Duggin, Geoffrey

    2002-06-01

    We present an interesting case of salicylism arising from the use of methyl salicylate as part of a herbal skin cream for the treatment of psoriasis. A 40-year-old man became quite suddenly and acutely unwell after receiving treatment from an unregistered naturopath. Methyl salicylate (Oil of Wintergreen) is widely available in many over the counter topical analgesic preparations and Chinese medicated oils. Transcutaneous absorption of the methyl salicylate was enhanced in this case due to the abnormal areas of skin and use of an occlusive dressing. The presence of tinnitus, vomiting, tachypnoea and typical acid/base disturbance allowed a diagnosis of salicylate toxicity to be made. Our patient had decontaminated his skin prior to presentation, limiting the extent of toxicity and was successfully treated with rehydration and establishment of good urine flow. PMID:12147116

  14. Sinus Node Dysfunction After Acute Lithium Treatment at Therapeutic Levels

    PubMed Central

    Nakatsu, Keigo; Nagamine, Takahiko

    2015-01-01

    Lithium carbonate (lithium) has been used extensively for the treatment of a variety of psychiatric conditions. It requires close monitoring of serum concentration due to its narrow therapeutic window. Cardiac toxicity range from asymptomatic electrocardiographic changes to fatal arrhythmias may occur even at the therapeutic levels. We report a case of psychiatric inpatient who developed asymptomatic severe bradycardia most likely related to sinus node dysfunction due to acute lithium treatment at therapeutic level. After withdrawal of lithium, a time sequential improvement of severe bradycardia examined by repeated electrocardiogram, including Holter monitoring, suggested a relationship between the lithium toxicity and sinus node dysfunction. Other factors such as baseline sinus bradycardia and lower limit of normal thyroid function might be associated with severe bradycardia. This case emphasizes the need, when prescribing lithium, for clinicians to regularly monitor their patients’ electrocardiogram and serum lithium levels to prevent serious or fatal complications, such as cardiac arrest. PMID:27222761

  15. Biology and treatment of adult acute lymphoblastic leukemia.

    PubMed Central

    Levitt, L; Lin, R

    1996-01-01

    The molecular analysis of acute lymphoblastic leukemia (ALL) has provided exciting insights into the pathogenesis of this disease. This disease is heterogenous and can be subtyped based on chromosomal, immunophenotypic, and structural criteria. The varying prognostic implications of different ALL subtypes markedly influence the treatment decisions in adults. Many patients with T-cell ALL can be cured with chemotherapy alone. In contrast, patients with early B-lineage ALL with certain chromosomal abnormalities, especially the Philadelphia chromosome, do not have durable responses to chemotherapy and should receive a bone marrow transplantation if an HLA-matched donor is available. Recent reports have shown improved results for adults with B-cell ALL (Burkitt's) after intensive alternating cycles of chemotherapy containing high doses of methotrexate and cyclophosphamide. Future clinical and laboratory investigation should lead to the development of novel and possibly more effective treatments specifically tailored for different subsets of ALL. PMID:8775728

  16. 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. PMID:25169208

  17. Emerging New Approaches for the Treatment of Acute Promyelocytic Leukemia

    PubMed Central

    Park, Jae; Jurcic, Joseph G.; Rosenblat, Todd; Tallman, Martin S.

    2011-01-01

    The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined with anthracycline-based chemotherapy has revolutionized the prognosis of acute promyelocytic leukemia (APL) with more than 90% complete response rates and cure rates of approximately 80%. The subsequent advent of arsenic trioxide (ATO) in 1990s and progress in the treatment of APL have changed its course from a highly fatal to a highly curable disease. Despite the dramatic improvement in clinical outcome of APL, treatment failure still occurs due most often to early death. Relapse has become increasingly less frequent, most commonly occurring in patients with high-risk disease. A major focus of research for the past decade has been to develop risk-adapted and rationally targeted nonchemotherapy treatment strategies to reduce treatment-related morbidity and mortality to low- and intermediate-risk or older patients while targeting more intensive or alternative therapy to those patients at most risk of relapse. In this review, emerging new approaches to APL treatment with special emhasis on strategies to reduce early deaths, risk-adapted therapy during induction, consolidation and maintenance, as well as an overview of current and future clinical trials in APL will be discussed. PMID:23556100

  18. [The new possibility for the treatment of acute cough].

    PubMed

    Klyachkina, I L

    2015-01-01

    ) can be recommended for the inclusion in the combined treatment of the patients presenting with acute and chronic diseases accompanied by the excretion of viscous and difficult-of-discharge bronchial mucus (such as acute and chronic bronchitis, pneumonia, chronic obstructive pulmonary disease, bronchial asthma with difficulty in sputum discharge, and bronchoectatic disease). PMID:26525480

  19. 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…

  20. Minocycline-Induced Cutaneous Hyperpigmentation in an Orthopedic Patient Population

    PubMed Central

    Hanada, Yuri; Berbari, Elie F.; Steckelberg, James M.

    2016-01-01

    Background. The objectives of this study were to estimate the incidence and evaluate risk factors for development of minocycline-induced cutaneous hyperpigmentation in patients with orthopedic infections. Methods. Patients with orthopedic infections evaluated at Mayo Clinic (Rochester, MN) and treated with minocycline from 1 January 2002 to 31 December 2011 were retrospectively identified. Long-term minocycline suppression was defined as daily minocycline use for at least 3 months. A proportional hazards model was used to evaluate potential risk factors. Results. Of 291 patients receiving long-term minocycline suppression, 54% (156 of 291) developed hyperpigmentation after a mean follow-up of 4.8 years (range, 0.3–13.2 years); 88% involved blue-gray pigmentation of normal skin that appeared most commonly in the lower (75%) and upper extremities (44%). The mean duration of minocycline therapy before hyperpigmentation was 1.5 years (range, 0.1–9 years) with a mean cumulative dosage of 107.3 g (range, 8.6–657 g). Notable risk factors include a history of vitamin D deficiency (relative risk [RR], 6.29; 95% confidence interval [CI], 1.91–15.27; P = .0052), presence of a shoulder prosthesis (RR, 3.2; 95% CI, 1.23–6.56; P = .0062), noncirrhotic liver pathology (RR, 3.63; 95% CI, 1.11–8.75; P = .0359), and use of a concurrent medication also known to cause hyperpigmentation (RR, 4.75; 95% CI, 1.83–10.1; P = .0029). Conclusions. Hyperpigmentation associated with the use of long-term minocycline suppression in patients with orthopedic infections is common. PMID:26835479

  1. [Consensus document on the diagnosis and treatment of acute tonsillopharyngitis].

    PubMed

    Piñeiro Pérez, R; Hijano Bandera, F; Alvez González, F; Fernández Landaluce, A; Silva Rico, J C; Pérez Cánovas, C; Calvo Rey, C; Cilleruelo Ortega, M J

    2011-11-01

    Acute tonsillopharyngitis is one of the most common childhood diseases. Viruses are the most frequent origin. Group A Streptococcus (Streptococcus pyogenes) is the main bacterial cause. A culture or a rapid antigen-detection test of a throat-swab specimen should only be done on the basis of clinical scores, in order to avoid over-diagnosis of bacterial origin and unnecessary antibiotic prescription. The objectives of treatment are: the reduction of symptoms, reduce the contagious period, and prevent local suppurative and systemic complications. Ideally, only confirmed cases should receive antibiotics. If there is no possibility to perform a rapid antigen-detection test, or in some cases if the result is negative, it is recommended to perform a culture and, if there is high suspicious index, to prescribe antibiotics. Penicillin is the treatment of choice, although amoxicillin is also accepted as the first option. Amoxicillin/clavulanate is not indicated in any case as empirical treatment. Macrolides are not a first choice antibiotic, and should be reserved for those patients with immediate penicillin allergy reaction or for the treatment of streptococcal carriers. It is of primordial importance to adapt the prescribing of antibiotics to the scientific evidence. PMID:21920830

  2. Severe Acute Axonal Neuropathy following Treatment with Arsenic Trioxide for Acute Promyelocytic Leukemia: a Case Report

    PubMed Central

    Kühn, Marcus; Sammartin, Kety; Nabergoj, Mitja; Vianello, Fabrizio

    2016-01-01

    Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide. PMID:27158436

  3. A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4.

    PubMed

    Bastos, Leandro F S; Godin, Adriana M; Zhang, Yingning; Jarussophon, Suwatchai; Ferreira, Bruno C S; Machado, Renes R; Maier, Steven F; Konishi, Yasuo; de Freitas, Rossimiriam P; Fiebich, Bernd L; Watkins, Linda R; Coelho, Márcio M; Moraes, Márcio F D

    2013-05-24

    Many studies have shown that minocycline, an antibacterial tetracycline, suppresses experimental pain. While minocycline's positive effects on pain resolution suggest that clinical use of such drugs may prove beneficial, minocycline's antibiotic actions and divalent cation (Ca(2+); Mg(2+)) chelating effects detract from its potential utility. Thus, we tested the antiallodynic effect induced by a non-antibacterial, non-chelating minocycline derivative in a model of neuropathic pain and performed an initial investigation of its anti-inflammatory effects in vitro. Intraperitoneal minocycline (100mg/kg) and 12S-hydroxy-1,12-pyrazolinominocycline (PMIN; 23.75 mg/kg, 47.50mg/kg or 95.00 mg/kg) reduce the mechanical allodynia induced by chronic constriction injury of mouse sciatic nerve. PMIN reduces the LPS-induced production of PGE2 by primary microglial cell cultures. Human embryonic kidney cells were transfected to express human toll-like receptors 2 and 4, and the signaling via both receptors stimulated with PAM3CSK4 or LPS (respectively) was affected either by minocycline or PMIN. Importantly, these treatments did not affect the cell viability, as assessed by MTT test. Altogether, these results reinforce the evidence that the anti-inflammatory and experimental pain suppressive effects induced by tetracyclines are neither necessarily linked to antibacterial nor to Ca(2+) chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the management of neuropathic pain, as its lack of antibacterial and Ca(2+) chelating activities might confer greater safety over conventional tetracyclines. PMID:23523650

  4. [Acute necrotizing pancreatitis--diagnostic and treatment strategy].

    PubMed

    Madzhov, R; Georgiev, K; Arnaudov, P; Radev, R; Bankov, P

    2003-01-01

    Despite of the current achievements of medicine, the mortality of necrotizing pancreatitis (NP) is still too high--up to 35-40% and stands as a serious diagnostic and treatment problem. The results of treatment of 148 patients, admitted in the clinic with diagnosis NP, 95 males and 53 females, are discussed. The ratio between patients with acute oedematic and acute NP is 81.1% to 18.9%. According to the hystopatology findings, the results are as follows: pancreatic necrosis--128 patients, peripancreatic necrosis--42 patients, retropancreatic necrosis--29 patients, phlegmonous cholecystitis--31 patients. For the exact diagnostic estimation of the development and prognosis of NP, we are based on: Clinic symptomatology, biochemical constellations (the prognostic scale of Ranson), ultrasonography, CT, ERCP, ES, laparoscopy (48 pts), and laparoscopic drainage (34 pts) of the abdominal cavity with one or two drains, in order to decrease the intoxication and manage intraperitoneal irrigation with antibiotics and enzymes. The operative intervations consists of a thorough exploration, broad necrectomy combined with lavage and large drainage. COLD (controlled open lesser sac drainage) has been performed at 34 cases. In 31 pts cholecystectomy and choledochotomy with T-tube drainage of d. choledochus (Kehr drainage) was performed. Reoperations have been made at 34 pts (22.9%); in 11 of them--2 operative revisions have been carried out, in 3 cases--three, and in 3 cases--4 operative revisions were performed. The total postoperative death rate was 21.6% (32 patients). The most common postoperative complications were as follows: pulmonary complications at 11 cases, pleural effusions--9 pts, intraabdominal abscesses--6 patients, postnecrotic pseudocysts--9 cases, pancreatic fistulas--6 cases, fistulas of the colon--2 pts, bleeding--4 patients. PMID:15584453

  5. [Peri-interventional management of acute endovascular stroke treatment].

    PubMed

    Schönenberger, S; Bösel, J

    2015-10-01

    Due to the ground breaking consistent evidence that supports the effect of endovascular stroke treatment (EST), many acute care hospitals and stroke centers will have to be prepared to provide this treatment in an optimal way within the coming years. In addition to the intervention itself, patient preparation, stabilization and monitoring during the treatment as well as the aftercare represent significant challenges and have mostly not yet been sufficiently investigated. Under these aspects, the questions of optimal sedation and airway management have received the highest attention. Based on retrospective study results it already seems to be justified, respecting certain criteria, to prefer EST with the patient under conscious sedation (CS) in comparison to general anesthesia (GA) and to only switch to GA in cases of emergency until this question has been clarified by prospective studies. This and other aspects of peri-interventional management, such as logistics, monitoring, blood pressure, ventilation settings, postprocedural steps of intensive or stroke unit care and imaging follow-up are summarized in this overview. The clinical and radiological selection of patients and thus the decision for intervention or technical aspects of the intervention itself will not be part of this article. PMID:26311331

  6. Plasmapheresis in Acute Fatty Liver of Pregnancy: An Effective Treatment

    PubMed Central

    Seyyed Majidi, Mohammad Reza

    2013-01-01

    Acute fatty liver of pregnancy (AFLP) is an idiopathic disorder with an unknown cause occurring in late pregnancy. The treatment in these patients is often immediate termination of pregnancy, and plasmapheresis provides an effective treatment option. In this paper, we introduce three pregnant women treated with plasmapheresis. The first case was a 22-year-old primigravida woman treated with 22 sessions of plasmapheresis due to AFLP, hepatic and renal failure, coagulopathy, and ventilator-dependent respiratory failure. The second case was a 23-year-old woman in her second pregnancy treated with 4 plasmapheresis sessions due to AFLP, hepatic and renal failure, coagulopathy, and hypoglycemia. The third patient was a 23-year-old primigravida woman treated with 3 plasmapheresis sessions due to AFLP, renal failure, and coagulopathy. Plasmapheresis can be a life-saving treatment in patients with AFLP and is strongly recommended for patients with severity of their disease accompanied by other organ disorders. In addition, shortening the time interval between the termination of pregnancy and initializing plasmapheresis improves the outcome and reduces the duration of hospital stay and sessions of plasmapheresis. PMID:23424692

  7. Attenuation of morphine tolerance by minocycline and pentoxifylline in naive and neuropathic mice.

    PubMed

    Mika, Joanna; Wawrzczak-Bargiela, Agnieszka; Osikowicz, Maria; Makuch, Wioletta; Przewlocka, Barbara

    2009-01-01

    We have previously demonstrated that glial inhibitors reduce the development of allodynia and hyperalgesia, potentiating the effect of a single morphine dose in a neuropathic pain model. This study explores the effects of two glial activation inhibitors, minocycline and pentoxifylline, on the development of tolerance to morphine in naive and chronic constriction injury (CCI)-exposed mice. Administration of morphine to naive (20 mg/kg; i.p.) and CCI-exposed mice (40 mg/kg; i.p.) twice daily resulted in tolerance to its anti-nociceptive effect after 6 days. Injections of morphine were combined with minocycline (30 mg/kg, i.p.) or pentoxifylline (20 mg/kg, i.p.) administered as two preemptive doses before first morphine administration in naive or pre-injury in CCI-exposed mice, and repeated twice daily 30 min before each morphine administration. With treatment, development of morphine tolerance was delayed by 5 days (from 6 to 11 days), as measured by the tail-flick test in naive and by tail-flick, von Frey, and cold plate tests in CCI-exposed mice. Western blot analysis of CD11b/c and GFAP protein demonstrated that minocycline and pentoxifylline, at doses delaying development of tolerance to morphine analgesia, significantly diminished the morphine-induced increase in CD11b/c protein level. We found that repeated systemic administration of glial inhibitors significantly delays development of morphine tolerance by attenuating the level of this microglial marker under normal and neuropathic pain conditions. Our results support the idea that targeting microglial activation during morphine therapy/treatment is a novel and clinically promising method for enhancing morphine's analgesic effects, especially in neuropathic pain. PMID:18684397

  8. Treatment of Acute HIV Infection and the Potential Role of Acutely HIV-Infected Persons in Cure Studies.

    PubMed

    Little, Susan J

    Diagnosis of acute HIV infection is important for accurate estimation of HIV incidence, identifying persons who are unaware of their HIV infection, and offering immediate treatment and risk-reduction strategies. The higher viral loads associated with acute HIV infection are associated with an increased risk of transmission. Current treatment recommendations are the same for acute and established infections. Studies of acute HIV infection indicate that initiation of antiretroviral therapy during this period may allow greater recovery of CD4+ T-cell count and function and may result in a smaller latent viral reservoir and a skewing of infection away from central memory CD4+ T cells toward shorter-lived transitional memory CD4+ T cells. This article summarizes a presentation by Susan J. Little, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Los Angeles, California, in April 2015. PMID:27398768

  9. How assess drugs in the treatment of acute bipolar mania?

    PubMed

    Bourin, Michel; Thibaut, Florence

    2013-01-01

    Bipolar affective disorder is a serious mental disease associated with significant morbidity and mortality. Good-quality research available to guide treatment strategies remains insufficient, particularly with regard to manic or hypomanic episodes. A critical review of the various stages of mania might be helpful for pharmaceutical companies and investigators as a prerequisite for the clinical evaluation of potential antimanic properties of medications. The main difficulty is with a comparison between anticonvulsants, antipsychotics, and mood stabilizers such as lithium (with equal efficacy in the acute phase and the prevention of recurrent manic episodes). No consensus has been reached with regard to the treatment of bouts of acute mania in various parts of the world. Controlled clinical trials have, at last, provided irrefutable evidence of the activity of lithium, which has long been used alone, as well as that of divalproate or its derivatives and, to a lesser extent, carbamazepine. The new antipsychotic agents have more recently established their efficacy, especially aripiprazole, asenapine, quetiapine; olanzapine, risperidone, and ziprasidone (not sure where the paradox is). In Europe, haloperidol is still the reference substance used in clinical trials despite the fact that it is not officially indicated in the treatment of mania. In the USA, lithium, divalproate, or antipsychotics can be prescribed as first-line treatment. In Europe, lithium remains the first-line medication, whereas divalproate and atypical antipsychotic agents are used only as second-line therapy. Although both types of medication (antipsychotics, normothymic agents, and/or anticonvulsants) have proved to be clinically effective in the management of mania by reducing the mania scores overall, the same does not apply, however, to all symptoms of mania. Factorial approaches to mania have all shown that since there are several clinical forms of mania, several clusters of manic symptoms can

  10. New antiplatelet agents in the treatment of acute coronary syndromes.

    PubMed

    Sabouret, Pierre; Taiel-Sartral, Magali

    2014-03-01

    Effective antagonism of the P2Y12 platelet receptor is central to the treatment of acute coronary syndrome (ACS) patients, especially in the setting of percutaneous coronary intervention and stenting. According to consensus guidelines, early revascularization and intensive antiplatelet therapy are key to reducing the complications that arise from myocardial ischaemia and the recurrence of cardiovascular events. Until recently, clopidogrel was the key P2Y12 antagonist advocated, but due to several limitations as an antiplatelet agent, newer drugs with more predictable, rapid and potent effects have been developed. Prasugrel and ticagrelor are now the recommended first-line agents in patients presenting with non-ST-segment elevation ACS and ST-segment elevation ACS, due to large-scale randomized trials that demonstrated net clinical benefit of these agents over clopidogrel, as stated in the European guidelines. Although no study has directly compared the two agents, analysis of the data to date suggests that certain patient types, such as diabetics, those with ST-segment elevation myocardial infarction or renal failure and the elderly may have a better outcome with one agent over the other. Further studies are needed to confirm these differences and answer pending questions regarding the use of these drugs to optimize efficacy while minimizing adverse events, such as bleeding. The aim of this review is to provide an overview of the current P2Y12 receptor antagonists in the treatment of ACS, with a focus on issues of appropriate agent selection, timing of treatment, bleeding risk and the future role of personalized treatment using platelet function and genetic testing. PMID:24630752

  11. 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. PMID:27106204

  12. 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.

  13. Evaluation of artemisinins for the treatment of acute myeloid leukemia

    PubMed Central

    Drenberg, Christina D.; Buaboonnam, Jassada; Orwick, Shelley J.; Hu, Shuiying; Li, Lie; Fan, Yiping; Shelat, Anang A.; Guy, R. Kiplin; Rubnitz, Jeffrey

    2016-01-01

    Purpose Investigate antileukemic activity of artemisinins, artesunate (ART), and dihydroartemisinin (DHA), in combination with cytarabine, a key component of acute myeloid leukemia (AML) chemotherapy using in vitro and in vivo models. Methods Using ten human AML cell lines, we conducted a high-throughput screen to identify antimalarial agents with antileukemic activity. We evaluated effects of ART and DHA on cell viability, cytotoxicity, apoptosis, lysosomal integrity, and combination effects with cytarabine in cell lines and primary patient blasts. In vivo pharmacokinetic studies and efficacy of single-agent ART or combination with cytarabine were evaluated in three xenograft models. Results ART and DHA had the most potent activity in a panel of AML cell lines, with selectivity toward samples harboring MLL rearrangements and FLT3-ITD mutations. Combination of ART or DHA was synergistic with cytarabine. Single-dose ART (120 mg/kg) produced human equivalent exposures, but multiple dose daily administration required for in vivo efficacy was not tolerated. Combination treatment produced initial regression, but did not prolong survival in vivo. Conclusions The pharmacology of artemisinins is problematic and should be considered in designing AML treatment strategies with currently available agents. Artemisinins with improved pharmacokinetic properties may offer therapeutic benefit in combination with conventional therapeutic strategies in AML. PMID:27125973

  14. Poor survival of treatment-related acute nonlymphocytic leukemia

    SciTech Connect

    Neugut, A.I. Nieves, J.; Murray, T.; Tsai, Weiyann ); Robinson, E. )

    1990-08-29

    Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973-1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6,271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL had an estimated 12-month survival of 10%. The authors conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients.

  15. Outcomes and humanistic issues related to treatment of acute bronchospasm.

    PubMed

    Okamoto, Lynn J

    2006-09-01

    Because of emergency department visits and hospitalizations, the economic costs associated with asthma, chronic obstructive pulmonary disease (COPD), and bronchospasm are a significant portion of total overall treatment costs. A small proportion of patients account for most of the costs, due to disease severity and acute exacerbations. Disease management programs, sponsored by insurance groups and employers, are lowering health and disability costs and reducing days missed from work and school because of exacerbations. Quality-of-life patient assessments are available to assist practitioners in evaluating disease status. Evidenced-based medicine analysis can show that less expensive therapies are not necessarily cost-effective. A study of the rate of hospital admissions from the emergency department showed that although levalbuterol therapy in the emergency department was more costly than racemic albuterol therapy, total overall treatment costs were reduced because of decreased hospitalizations in the levalbuterol-treated patients. Thus, providers, payers, and patients should examine all the scientific evidence (safety, efficacy or effectiveness, economics, and humanistic benefits) to make the most informed health care decision. PMID:16945064

  16. Treatment options for acute uncomplicated cystitis in adults.

    PubMed

    Naber

    2000-08-01

    Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of 10%) of Escherichia coli strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis. PMID:10969048

  17. Treatment options for acute uncomplicated cystitis in adults.

    PubMed

    Naber, K G

    2000-09-01

    Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of < or =10-20%. Otherwise fluoroquinolones are recommended. Alternatives are fosfomycin trometamol or beta-lactams, such as second- or third-generation oral cephalosporins or pivmecillinam, especially when fluoroquinolones are contraindicated or a high proportion (>10%) of Escherichia coil strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis. PMID:11051620

  18. Gastroprotective effect of minocycline in experimentally induced gastric ulcers in rats.

    PubMed

    Asmari, Abdulrahman Al; Omani, Saud Al; Otaibi, Malfi Al; Abdulaaly, Abdul-Aziz Al; Elfaki, Ibrahim; Yahya, Khalid Al; Arshaduddin, Mohammed

    2014-01-01

    Minocycline (MCN), a semi-synthetic tetracycline derivative possesses pleiotropic effects and provides protection against a number of disease models. However its effect on gastric ulcers has not been studied. The present investigation was undertaken, to study the gastro-protective potential of MCN in experimentally induced gastric ulcers in rats. MCN (10, 30, 100 mg/Kg) was tested for gastric secretion and antiulcer activity in different groups of Wistar rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) and indomethacin (30 mg/kg), induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and myeloperoxidase (MPO), were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ulcerogens resulted in gastric mucosal injury and a significant increase in the indices of ulcer. MCN conferred a protective effect against ethanol, and indomethacin induced gastric mucosal injuries. Treatment with MCN, resulted in a significant decrease in the amount of gastric secretion, and total acidity and significantly (P<0.001), reduced the gastric lesions induced by ethanol and indomethacin. MCN also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P<0.001). The histological changes and the increased MDA and MPO activity were also significantly (P<0.001) inhibited by MCN. Minocycline showed significant antiulcer and gastroprotective activity against experimentally induced gastric ulcers. The gastroprotective effects of minocycline may be due to its anti-secretory, antioxidant and anti inflammatory action. PMID:24753752

  19. Gastroprotective effect of minocycline in experimentally induced gastric ulcers in rats

    PubMed Central

    Asmari, Abdulrahman Al; Omani, Saud Al; Otaibi, Malfi Al; Abdulaaly, Abdul-Aziz Al; Elfaki, Ibrahim; Yahya, Khalid Al; Arshaduddin, Mohammed

    2014-01-01

    Minocycline (MCN), a semi-synthetic tetracycline derivative possesses pleiotropic effects and provides protection against a number of disease models. However its effect on gastric ulcers has not been studied. The present investigation was undertaken, to study the gastro-protective potential of MCN in experimentally induced gastric ulcers in rats. MCN (10, 30, 100 mg/Kg) was tested for gastric secretion and antiulcer activity in different groups of Wistar rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) and indomethacin (30 mg/kg), induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and myeloperoxidase (MPO), were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ulcerogens resulted in gastric mucosal injury and a significant increase in the indices of ulcer. MCN conferred a protective effect against ethanol, and indomethacin induced gastric mucosal injuries. Treatment with MCN, resulted in a significant decrease in the amount of gastric secretion, and total acidity and significantly (P<0.001), reduced the gastric lesions induced by ethanol and indomethacin. MCN also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P<0.001). The histological changes and the increased MDA and MPO activity were also significantly (P<0.001) inhibited by MCN. Minocycline showed significant antiulcer and gastroprotective activity against experimentally induced gastric ulcers. The gastroprotective effects of minocycline may be due to its anti-secretory, antioxidant and anti inflammatory action. PMID:24753752

  20. Minocycline, an antibiotic with inhibitory effect on microglial activation, attenuates the maintenance and reinstatement of methamphetamine-seeking behavior in rat.

    PubMed

    Attarzadeh-Yazdi, Ghassem; Arezoomandan, Reza; Haghparast, Abbas

    2014-08-01

    Methamphetamine (METH) is a major criminal justice and public health problem. Repeated use of METH causes dependence in humans and there are currently no particular pharmacological treatments for METH addiction. Glial cell activation is linked with METH abuse and METH administration causes activation of these cells in many areas of the brain. Many studies have demonstrated that glial cell modulators can modulate drug abuse effects. In this study, we examined the effect of the putative microglial inhibitor, minocycline on maintenance and prime-induced reinstatement of METH seeking behavior using the conditioned place preference (CPP) paradigm. CPP induced with METH (1 mg/kg, i.p. for 3 days) lasted for 11 days after cessation of METH treatment and priming dose of METH (0.5 mg/kg, i.p.) reinstated the extinguished METH-induced CPP. Daily treatment of minocycline (40 mg/kg, i.p.) followed by establishment of CPP blocked the maintenance of METH-induced CPP and also could attenuate priming-induced reinstatement. Furthermore, daily bilateral intra-accumbal injection of minocycline (10 and 20 μg/0.5 μl saline), during extinction period blocked the maintenance of METH CPP but just the highest dose of that could attenuate priming-induced reinstatement. We showed that minocycline administration during extinction period could facilitate extinction and maybe abolish the ability of drug-related cues evoke reinstatement, suggesting that minocycline might be considered as a promising therapeutic agent in preventing relapse in METH dependent individuals. PMID:24768984

  1. Technologies for diagnosis and treatment of acute stroke

    SciTech Connect

    Fitch, J.P.

    1998-02-09

    From October 1994 to June 1997, a multidisciplinary team of scientists and engineers at Lawrence Livermore National Laboratory were funded through LDRD to develop and integrate technologies for diagnosis and treatment of acute stroke. The project was summarized in a Science and Technology Review article `Brain Attack` that appeared in June 1997 and again in the Center for Healthcare Technologies Report (UCRL-LR-124761). This article is the best overview of the project, epidemiology of stroke and technical progress. Most of the technical progress has been documented in conference papers and presentations and refereed journal articles. Additional technical publication can be expected as our remaining patent applications progress through the US Patent and Trademark Office. The purpose of this report is to provide an appropriate introduction and organization to the numerous publications so that interested readers can quickly find information. Because there is no documentation for the history of this project, this report provides a summary. It also provides the final status report for the LDRD funding.

  2. Sumatriptan iontophoretic transdermal system for the acute treatment of migraine.

    PubMed

    Vikelis, Michail; Mitsikostas, Dimos D; Rapoport, Alan M

    2014-03-01

    SUMMARY We will describe the pharmacokinetic profile, clinical efficacy and safety data of the sumatriptan iontophoretic transdermal system (Zecuity®, NuPathe Inc., PA, USA), recently approved for the acute treatment of migraine with or without aura in adults, by the US FDA. This transdermal system utilizes a low-level electrical current to deliver sumatriptan transdermally and circumvents the GI tract. Pharmacokinetic studies have shown that iontophoretic delivery of sumatriptan achieves detectable plasma concentrations 15 min after activation with a maximum mean serum concentration of 22 ng/ml. A randomized, double-blind, controlled clinical trial demonstrated minimal triptan-related side effects and superior efficacy versus placebo. The pain-free rate at 2 h postdose was 18% of patients applying the sumatriptan patch versus 9% using the placebo (p = 0.0092). This sumatriptan transdermal system may be a good choice for migraineurs with severe nausea or vomiting, those with intolerable triptan-related adverse events and/or those not responding optimally to oral medications. PMID:24641436

  3. Genetics and Treatments Options for Recurrent Acute and Chronic Pancreatitis

    PubMed Central

    Shelton, Celeste A.; Whitcomb, David C.

    2014-01-01

    Opinion Statement Worldwide research efforts demonstrate a major role of gene-environment interactions for the risk, development, and progression of most pancreatic diseases, including recurrent acute and chronic pancreatitis. New findings of pancreas disease-associated risk variants have been reported in the CPA1, GGT1, CLDN2, MMP1, MTHFR, and other genes. These risk genes and their regulatory regions must be added to the known pathogenic variants in the PRSS1, SPINK1, CFTR, CTRC, CASR, UBR1, SBDS, CEL, and CTSB genes. This new knowledge promises to improve disease management and prevention through personalized medicine. At the same time, however, knowledge of an increasing number of pathogenic variants, and their complicated effects when present in combination, results in increasing difficulty in interpretation and development of recommendations. Direct-to-consumer marketing of genetic testing results also adds complexity to disease management paradigms, especially without interpretation and, in many cases, proven accuracy. While improvements in the ability to rapidly and accurately interpret complex genetic tests are clearly needed, some results, such as pathogenic CFTR variants – including a new class of bicarbonate-defective mutations – and PRSS1 variants have immediate implications that direct management. In addition, discovery of pancreatitis-associated genetic variants in patients with glucose intolerance may suggest underlying type 3c diabetes, which also has implications for treatment and disease management. PMID:24954874

  4. Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD.

    PubMed

    Perfetti, P; Carlier, P; Strada, P; Gualandi, F; Occhini, D; Van Lint, M T; Ibatici, A; Lamparelli, T; Bruno, B; Raiola, A M; Dominietto, A; Di Grazia, C; Bregante, S; Zia, S; Ferrari, G M; Stura, P; Pogliani, E; Bacigalupo, A

    2008-11-01

    Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n=10), III (n=7) or IV (n=6)). The median duration of ECP was 7 months (1-33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day +90 from ECP) (P=0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P=0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P=0.1). A trend for improved survival was seen in grade III-IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease. PMID:18660840

  5. Potentiation of aspirin-induced cerebroprotection by minocycline: a therapeutic approach to attenuate exacerbation of transient focal cerebral ischaemia.

    PubMed

    Bhatt, Lokesh K; Addepalli, Veeranjaneyulu

    2012-01-01

    Cerebrovascular disease is a major cause of mortality and disability in adults. Diabetes mellitus increases the risk of cerebral ischaemia and is associated with worse clinical outcome following an event. Upregulation of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in diabetes appears to play a role in vascular complications of diabetes. We hypothesised that inhibition of MMP-2 and MMP-9 by minocycline can be potentiated by aspirin through inhibition of cyclooxygenase-2 and tissue plasminogen activator, resulting in amelioration of clinical cerebral ischaemia in diabetes. In the present study, cerebral ischaemia/reperfusion injury was induced in streptozotocin diabetic rats by 1 h middle cerebral artery occlusion and 24 h reperfusion. Infarct volume, cerebral oedema, neurological severity score and blood-brain barrier disruption were significantly increased in diabetic animals compared with the normoglycemic control group. The combination of aspirin and minocycline treatment significantly improved these parameters in diabetic animals. Moreover, this therapy was associated with significantly lower mortality and reduction in MMP-2 and MMP-9 levels. Our data indicate that combination of aspirin and minocycline therapy protects from the consequences of cerebral ischaemia in animal models of diabetes and is associated with inhibition of MMP-2 and MMP-9. Therefore, this combination therapy may represent a novel strategy to reduce the neurological complications of cerebral ischaemia in diabetes. PMID:22045867

  6. The tetracycline analogs minocycline and doxycycline inhibit angiogenesis in vitro by a non-metalloproteinase-dependent mechanism.

    PubMed

    Gilbertson-Beadling, S; Powers, E A; Stamp-Cole, M; Scott, P S; Wallace, T L; Copeland, J; Petzold, G; Mitchell, M; Ledbetter, S; Poorman, R

    1995-01-01

    The tetracycline analogs minocycline and doxycycline are inhibitors of metalloproteinases (MMPs) and have been shown to inhibit angiogenesis in vivo. To further study the mechanism of action of these compounds we tested them in an in vitro model of angiogenesis: aortic sprouting in fibrin gels. Angiogenesis was quantitated in this system by a unique application of planar morphometry. Both compounds were found to potently inhibit angiogenesis in this model. To further characterize the activity of these compounds against MMPs, we determined the IC50S of both compounds against representatives of three classes of metalloproteinases: fibroblast collagenase, stromelysin, and gelatinase A. Doxycycline was found to inhibit collagenase, gelatinase A and stromelysin with IC50S of 452 microM, 56 microM and 32 microM, respectively. Minocycline was found to inhibit only stromelysin in the micromolar range with an IC50 of 290 microM. Since these results suggest that these compounds may not have been inhibiting in vitro angiogenesis by an MMP-dependent mechanism, we decided to test the effects of the potent MMP inhibitor BB-94. This compound failed to inhibit aortic sprouting in fibrin gels, thus strongly suggesting that both doxycycline and minocycline act by an MMP-independent mechanism. These results have implications for the mechanism of action of tetracycline analogs, particularly where they are being considered for the treatment of disorders of extracellular matrix degradation including periodontal disease, arthritis, and tumor angiogenesis. PMID:7543375

  7. Unrecognized acute exertional compartment syndrome of the leg and treatment.

    PubMed

    Popovic, Nebojsa; Bottoni, Craig; Cassidy, Charles

    2011-04-01

    Acute-on-chronic exertional compartment syndrome is rare and may be easily missed without a high degree of awareness and clinical suspicion. We report a case of unrecognized acute-on-chronic exertional compartment syndrome in a recreational soccer player. The late sequela of this condition, foot drop, was successfully treated with transfer of the peroneus longus tendon. PMID:21667742

  8. Sinus Balloon Dilation as Treatment for Acute Sphenoid Sinusitis with Impaired Vision for a Child

    PubMed Central

    Zhao, Yin; Chen, Kangbing; Wang, Zonggui

    2016-01-01

    This paper is about sinus balloon dilatation in treatment of acute left sphenoid sinusitis with left impaired vision in a child. Balloon catheter dilatation (BCD) of the sinus ostia is a new technique. It has been shown to be a minimally invasive technique to manage chronic sinusitis. However, this method is rarely used in the treatment of acute sinusitis. So far, we know of no reported cases of sinus balloon dilatation in treatment of this case, especially for children. PMID:27006660

  9. [Inefficacy of oral contraception during use of minocycline].

    PubMed

    de Groot, A C; Eshuis, H; Stricker, B H

    1990-06-23

    A healthy woman aged 21 years who used the oral contraceptive Trigynon became pregnant while being treated with Minocin (minocycline; 100 mg per day) for acne conglobata. While the risk of use of antibiotics such as this one reducing the efficacy of oral contraceptives is small, patients should nevertheless be informed that the risk exists. PMID:2143563

  10. [Acute poisoning with selected hepatotoxic agents: biochemistry of toxic effect, clinical symptoms and treatment].

    PubMed

    Rusiński, Piotr; Kołaciński, Zbigniew

    2003-01-01

    The paper discusses etiopathogenesis, clinical symptoms and treatment in acute poisoning with hepatotoxic agents. The liver is a critical organ in acute poisoning with Amanita phalloides, carbon tetrachloride, iron compounds and isonicotinic acid hydrazide. Based on literature reports and own experience the authors present the current outlook on the specific treatment of acute poisoning with these xenobiotics. Special consideration was given to biochemical etiopathogenesis of hepatoxicity: oxidative stress, lipid peroxidation and impaired homeostasis of calcium ions and glutathione. Basic principles were also discussed of conservative treatment in hepatic encephalopathy due to toxic liver necrosis. PMID:14569886

  11. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury.

    PubMed

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L J; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A; McDevitt, Michael R

    2016-03-23

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)-mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, includingTrp53,Mep1b,Ctr1, andEGFP A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1band fCNT/siTrp53significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  12. Midostaurin: an emerging treatment for acute myeloid leukemia patients

    PubMed Central

    Gallogly, Molly Megan; Lazarus, Hillard M

    2016-01-01

    Acute myeloid leukemia (AML) is a hematologic malignancy that carries a poor prognosis and has garnered few treatment advances in the last few decades. Mutation of the internal tandem duplication (ITD) region of fms-like tyrosine kinase (FLT3) is considered high risk for decreased response and overall survival. Midostaurin is a Type III receptor tyrosine kinase inhibitor found to inhibit FLT3 and other receptor tyrosine kinases, including platelet-derived growth factor receptors, cyclin-dependent kinase 1, src, c-kit, and vascular endothelial growth factor receptor. In preclinical studies, midostaurin exhibited broad-spectrum antitumor activity toward a wide range of tumor xenografts, as well as an FLT3-ITD-driven mouse model of myelodysplastic syndrome (MDS). Midostaurin is orally administered and generally well tolerated as a single agent; hematologic toxicity increases substantially when administered in combination with standard induction chemotherapy. Clinical trials primarily have focused on relapsed/refractory AML and MDS and included single- and combination-agent studies. Administration of midostaurin to relapsed/refractory MDS and AML patients confers a robust anti-blast response sufficient to bridge a minority of patients to transplant. In combination with histone deacetylase inhibitors, responses appear comparable to historic controls, while the addition of midostaurin to standard induction chemotherapy may prolong survival in FLT3-ITD mutant patients. The response of some wild-type (WT)-FLT3 patients to midostaurin therapy is consistent with midostaurin’s ability to inhibit WT-FLT3 in vitro, and also may reflect overexpression of WT-FLT3 in those patients and/or off-target effects such as inhibition of kinases other than FLT3. Midostaurin represents a well-tolerated, easily administered oral agent with the potential to bridge mutant and WT-FLT3 AML patients to transplant and possibly deepen response to induction chemotherapy. Ongoing studies are

  13. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury

    PubMed Central

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J.; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)–mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, including Trp53, Mep1b, Ctr1, and EGFP. A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1b and fCNT/siTrp53 significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  14. Treatment of acute lateral ankle ligament rupture in the athlete. Conservative versus surgical treatment.

    PubMed

    Lynch, S A; Renström, P A

    1999-01-01

    Acute lateral ankle ligament sprains are common in young athletes (15 to 35 years of age). Diagnostic and treatment protocols vary. Therapies range from cast immobilisation or acute surgical repair to functional rehabilitation. The lateral ligament complex includes 3 capsular ligaments: the anterior tibiofibular (ATFL), calcaneofibular (CFL) and posterior talofibular (PTFL) ligaments. Injuries typically occur during plantar flexion and inversion; the ATFL is most commonly torn. The CFL and the PTFL can also be injured and, after severe inversion, subtalar joint ligaments are also affected. Commonly, an athlete with a lateral ankle ligament sprain reports having 'rolled over' the outside of their ankle. The entire ankle and foot must be examined to ensure there are no other injuries. Clinical stability tests for ligamentous disruption include the anterior drawer test of ATFL function and inversion tilt test of both ATFL and CFL function. Radiographs may rule out treatable fractures in severe injuries or when pain or tenderness are not associated with lateral ligaments. Stress radiographs do not affect treatment. Ankle sprains are classified from grades I to III (mild, moderate or severe). Grade I and II injuries recover quickly with nonoperative management. A non-operative 'functional treatment' programme includes immediate use of RICE (rest, ice, compression, elevation), a short period of immobilisation and protection with a tape or bandage, and early range of motion, weight-bearing and neuromuscular training exercises. Proprioceptive training on a tilt board after 3 to 4 weeks helps improve balance and neuromuscular control of the ankle. Treatment for grade III injuries is more controversial. A comprehensive literature evaluation and meta-analysis showed that early functional treatment provided the fastest recovery of ankle mobility and earliest return to work and physical activity without affecting late mechanical stability. Functional treatment was complication

  15. Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

    PubMed

    Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

    2016-01-01

    Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy. PMID:26817927

  16. Activity of Tetracycline, Doxycycline, and Minocycline Against Methicillin-Susceptible and -Resistant Staphylococci

    PubMed Central

    Minuth, J. N.; Holmes, T. M.; Musher, D. M.

    1974-01-01

    Tetracycline, doxycycline, and minocycline were evaluated for their antibacterial activity against methicillin-susceptible and -resistant isolates of Staphylococcus. At clinically achievable levels both doxycycline and minocycline were more active than tetracycline against methicillin-susceptible organisms. Tetracycline and doxycycline had no activity against methicillin-resistant staphylococci, whereas minocycline at 2 μg/ml inhibited six of 13 strains and, at 3 μg/ml, 10 of 13 strains. PMID:4157335

  17. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    SciTech Connect

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E. . E-mail: cng@ohri.ca

    2005-05-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  18. A Pilot Study of Citalopram Treatment in Preventing Relapse of Depressive Episode after Acute Treatment

    PubMed Central

    Cheung, Amy; Levitt, Anthony; Cheng, Michael; Santor, Darcy; Kutcher, Stan; Dubo, Elyse; Jane Garland, E.; Weiss, Margaret; Kiss, Alex

    2016-01-01

    Purpose: To examine the benefit of continuation treatment with citalopram in adolescents 13 to 18 years of age with major depression using a multi-site randomized placebo controlled discontinuation design. Methods: Subjects with depression who responded to open label treatment with citalopram in 12-week acute phase were randomized to continued treatment with citalopram or placebo for 24 weeks. Results: Twenty five subjects were randomized to either continued treatment with citalopram (n = 12) versus placebo (n = 13). Seventy-five percent of subjects on citalopram (75%) remained well as compared to placebo (62%). Time to relapse was compared between groups using the log rank test and was not found to be significantly different (χ2(1) = 0.35, P = 0.55). A Cox proportional hazards model including drug assignment (hazard ratio (HR = 0.51, 95% CI 0.11 to 2.36, P = 0.39), gender (HR = 0.58, 95% CI 0.14 to 2.37, P = 0.44), or HAM-score at entry to continuation phase (HR = 1.33, 95% CI 0.90 to 1.95, P = 0.95) was not significant. Conclusion: Although we did not find statistically significant differences between citalopram and placebo, the findings suggest a possible benefit of continued treatment with citalopram over placebo. A larger clinical trial with adequate power is required to confirm or disconfirm these findings. PMID:27047552

  19. Maternal Depressive Symptoms in Pediatric Major Depressive Disorder: Relationship to Acute Treatment Outcome

    ERIC Educational Resources Information Center

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

    2008-01-01

    A study examined maternal depressive symptoms at the beginning and end of acute pediatric treatment of children with major depressive disorder (MDD). Results suggested a direct and possible reciprocal association between maternal and child depression severity.

  20. Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria.

    PubMed

    Harper, Pauline; Wahlin, Staffan

    2007-12-01

    The porphyrias are a group of uncommon metabolic diseases caused by enzyme deficiencies within heme biosynthesis that lead to neurotoxic or phototoxic heme precursor accumulation. There are four acute porphyrias characterized by neuropsychiatric symptoms: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and 5-aminolevulinic acid dehydratase deficiency porphyria. Treatment includes elimination of any porphyrogenic factor and symptomatic treatment. Carbohydrate and intravenous heme administration constitute specific therapies in the disorders' acute phase. The mainstay treatment in the cutaneous porphyrias is avoidance of sunlight exposure. In porphyria cutanea tarda and the two acute porphyrias with skin manifestations, variegate porphyria and hereditary coproporphyria, care of the vulnerable skin is important. In porphyria cutanea tarda, specific treatment is accomplished by a series of phlebotomies and/or by low-dose chloroquine administration. In erythropoietic protoporphyria, light-protective beta-carotene is prescribed. PMID:18221605

  1. 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. PMID:27246804

  2. Neuroprotection by Minocycline Caused by Direct and Specific Scavenging of Peroxynitrite*

    PubMed Central

    Schildknecht, Stefan; Pape, Regina; Müller, Nathalie; Robotta, Marta; Marquardt, Andreas; Bürkle, Alexander; Drescher, Malte; Leist, Marcel

    2011-01-01

    Minocycline prevents oxidative protein modifications and damage in disease models associated with inflammatory glial activation and oxidative stress. Although the drug has been assumed to act by preventing the up-regulation of proinflammatory enzymes, we probed here its direct chemical interaction with reactive oxygen species. The antibiotic did not react with superoxide or •NO radicals, but peroxynitrite (PON) was scavenged in the range of ∼1 μm minocycline and below. The interaction of pharmacologically relevant minocycline concentrations with PON was corroborated in several assay systems and significantly exceeded the efficacy of other antibiotics. Minocycline was degraded during the reaction with PON, and the resultant products lacked antioxidant properties. The antioxidant activity of minocycline extended to cellular systems, because it prevented neuronal mitochondrial DNA damage and glutathione depletion. Maintenance of neuronal viability under PON stress was shown to be solely dependent on direct chemical scavenging by minocycline. We chose α-synuclein (ASYN), known from Parkinsonian pathology as a biologically relevant target in chemical and cellular nitration reactions. Submicromolar concentrations of minocycline prevented tyrosine nitration of ASYN by PON. Mass spectrometric analysis revealed that minocycline impeded nitrations more effectively than methionine oxidations and dimerizations of ASYN, which are secondary reactions under PON stress. Thus, PON scavenging at low concentrations is a novel feature of minocycline and may help to explain its pharmacological activity. PMID:21081502

  3. Advances in the treatment of acute graft-versus-host disease

    PubMed Central

    Qian, Liren; Wu, Zhengcheng; Shen, Jianliang

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has been widely used for the treatment of hematologic malignant and non-malignant hematologic diseases and other diseases. However, acute graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic transplantation. Acute GVHD may occur in 30% of transplant recipients, which is a syndrome of erythematous skin eruption, cholestatic liver disease and intestinal dysfunction, resulting from the activation of donor T lymphocytes by host antigen-presenting cells, resulting in an immune-mediated inflammatory response. Recent scientific advances in the understanding of the pathogenesis involved in the development of acute GVHD and clinical investigation have provided more effective therapeutic strategies for acute GVHD. This review focuses on major scientific and clinical advances in the treatment of acute GVHD. PMID:23802653

  4. A 2 × 2 factorial design for the combination therapy of minocycline and remote ischemic perconditioning: efficacy in a preclinical trial in murine thromboembolic stroke model

    PubMed Central

    2014-01-01

    Background After the failure of so many drugs and therapies for acute ischemic stroke, innovative approaches are needed to develop new treatments. One promising strategy is to test combinations of agents in the pre-hospital setting prior to the administration of intravenous tissue plasminogen activator (IV-tPA) and/ or the use of mechanical reperfusion devices in the hospital. Methods We performed a 2 × 2 factorial design preclinical trial where we tested minocycline (MINO), remote ischemic perconditioning (RIPerC) and their combination treatment in a thromboembolic clot model of stroke in mice, without IV-tPA or later treated with IV-tPA at 4 hours post-stroke. Cerebral blood flow (CBF) was measured by laser speckle contrast imaging (LSCI), behavioral outcomes as neurological deficit score (NDS) and adhesive tape removal test, and infarct size measurement were performed at 48 hours post-stroke. Mice within the experimental sets were randomized for the different treatments, and all outcome measures were blinded. Results RIPerC significantly improved CBF as measured by LSCI in both with and without tPA treated mice (P < 0.001). MINO and RIPerC treatment were effective alone at reducing infarct size (p < 0.0001) and improving short-term functional outcomes (p < 0.001) in the tPA and non-tPA treated animals. The combination treatment of MINO and RIPerC significantly reduced the infarct size greater than either intervention alone (p < 0.05). There were trends in favor of improving functional outcomes after combination treatment of MINO and RIPerC; however combination treatment group was not significantly different than the individual treatments of MINO and RIPerC. There was no “statistical” interaction between minocycline and RIPerC treatments indicating that the effects of RIPerC and MINO were additive and not synergistic on the outcome measures. Conclusion In the future, combining these two safe and low cost interventions in the ambulance

  5. ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults.

    PubMed

    Riddle, Mark S; DuPont, Herbert L; Connor, Bradley A

    2016-05-01

    Acute diarrheal infections are a common health problem globally and among both individuals in the United States and traveling to developing world countries. Multiple modalities including antibiotic and non-antibiotic therapies have been used to address these common infections. Information on treatment, prevention, diagnostics, and the consequences of acute diarrhea infection has emerged and helps to inform clinical management. In this ACG Clinical Guideline, the authors present an evidence-based approach to diagnosis, prevention, and treatment of acute diarrhea infection in both US-based and travel settings. PMID:27068718

  6. Early Treatment of Severe Acute Respiratory Distress Syndrome.

    PubMed

    Przybysz, Thomas M; Heffner, Alan C

    2016-02-01

    Acute respiratory distress syndrome (ARDS) is defined by acute diffuse inflammatory lung injury invoked by a variety of systemic or pulmonary insults. Despite medical progress in management, mortality remains 27% to 45%. Patients with ARDS should be managed with low tidal volume ventilation. Permissive hypercapnea is well tolerated. Conservative fluid strategy can reduce ventilator and hospital days in patients without shock. Prone positioning and neuromuscular blockers reduce mortality in some patients. Early management of ARDS is relevant to emergency medicine. Identifying ARDS patients who should be transferred to an extracorporeal membrane oxygenation center is an important task for emergency providers. PMID:26614238

  7. Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.

    PubMed

    Asher, Alice; Lum, Paula J; Page, Kimberly

    2012-01-01

    Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111

  8. Assessing Candidacy for Acute Hepatitis C Treatment Among Active Young Injection Drug Users: A Case-Series Report

    PubMed Central

    Asher, Alice; Lum, Paula J.; Page, Kimberly

    2011-01-01

    Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All 5 acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. . Establishing treatment candidacy for young IDU in the acute phase involves various health domains. Acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111

  9. Early treatment of hypertension in acute ischemic and intracerebral hemorrhagic stroke: progress achieved, challenges, and perspectives.

    PubMed

    Feldstein, Carlos A

    2014-03-01

    Hypertension is the leading risk factor for ischemic and intracerebral hemorrhagic subtypes of stroke. Additionally, high blood pressure (BP) in the acute cerebrovascular event is associated with poor outcome, and a high percentage of stroke survivors have inadequate control of hypertension. The present is a systematic review of prospective, randomized, and controlled trials carried out on safety and efficacy of antihypertensive treatment of both subtypes of acute stroke. Six trials involving 7512 patients were included, which revealed controversies on the speed and the goals of treatment. These controversies could be due at least in part, from the fact that some studies analyzed the results of antihypertensive treatment in ischemic and intracerebral hemorrhagic subtypes of acute stroke together, and from a different prevalence of past-stroke in the randomized groups. Further research is necessary to establish whether standard antihypertensive treatment provides greater benefit than simple observation in patients with ischemic acute stroke and Stage 2 hypertension of JNC 7, albeit they were not candidates for acute reperfusion. In that case, the target reduction in BP could be 10% to 15% within 24 hours. The recently published INTERACT 2 has provided evidence that patients with hemorrhagic stroke may receive intensive antihypertensive treatment safely with the goal of reducing systolic BP to levels no lower than 130 mm Hg. It is important to take into account that marked BP lowering in acute stroke increases the risk of poor outcome by worsening cerebral ischemia from deterioration of cerebral blood flow autoregulation. PMID:24220549

  10. Diagnosis and Treatment of Acute Gout at a University Hospital Emergency Department

    PubMed Central

    Schlesinger, Naomi; Radvanski, Diane C; Young, Tina C; McCoy, Jonathan V; Eisenstein, Robert; Moore, Dirk F

    2015-01-01

    Background : Acute gout attacks account for a substantial number of visits to the emergency department (ED). Our aim was to evaluate acute gout diagnosis and treatment at a University Hospital ED. Methods : Our study was a retrospective chart review of consecutive patients with a diagnosis of acute gout seen in the ED 1/01/2004 - 12/31/2010. We documented: demographics, clinical characteristics, medications given, diagnostic tests, consultations and whether patients were hospitalized. Descriptive and summary statistics were performed on all variables. Results : We found 541 unique ED visit records of patients whose discharge diagnosis was acute gout over a 7 year period. 0.13% of ED visits were due to acute gout. The mean patient age was 54; 79% were men. For 118 (22%) this was their first attack. Attack duration was ≤ 3 days in 75%. Lower extremity joints were most commonly affected. Arthrocentesis was performed in 42 (8%) of acute gout ED visits. During 355 (66%) of ED visits, medications were given in the ED and/or prescribed. An anti-inflammatory drug was given during the ED visit during 239 (44%) visits. Medications given during the ED visit included: NSAIDs: 198 (56%): opiates 190 (54%); colchicine 32 (9%) and prednisone 32 (9%). During 154 (28%) visits an anti-inflammatory drug was prescribed. Thirty two (6%) were given no medications during the ED visit nor did they receive a prescription. Acute gout rarely (5%) led to hospitalizations. Conclusion : The diagnosis of acute gout in the ED is commonly clinical and not crystal proven. Anti-inflammatory drugs are the mainstay of treatment in acute gout; yet, during more than 50% of ED visits, anti-inflammatory drugs were not given during the visit. Thus, improvement in the diagnosis and treatment of acute gout in the ED may be required. PMID:26106456

  11. Communication Disorders and Treatment in the Acute Trauma Center Setting.

    ERIC Educational Resources Information Center

    Schwartz-Cowley, Roberta; Stepanik, Mark J.

    1989-01-01

    The Shock Trauma Center of the Maryland Institute for Emergency Medical Services Systems instituted a comprehensive speech-language pathology program to provide acute intervention for communicative disorders in a critical/intensive care environment. This article provides a profile of the Center, a review of communicative impairments, and examples…

  12. Acute Stress Disorder: Conceptual Issues and Treatment Outcomes

    ERIC Educational Resources Information Center

    Koucky, Ellen M.; Galovski, Tara E.; Nixon, Reginald D. V.

    2012-01-01

    Acute stress disorder (ASD) was included as a diagnosis to the 4th edition of the "Diagnostic and Statistical Manual" (American Psychiatric Association, 1994) as a way of describing pathological reactions in the first month following a trauma. Since that time, ASD has been the focus of some controversy, particularly regarding the theoretical basis…

  13. Endovascular Treatment of Acute and Chronic Thoracic Aortic Injury

    SciTech Connect

    Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan

    2007-11-15

    Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.

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

    PubMed Central

    Lipton, Richard B.; Fanning, Kristina M.; Serrano, Daniel; Reed, Michael L.; Cady, Roger

    2015-01-01

    Objective: 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). Methods: 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. Results: 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. Conclusion: 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. PMID:25609757

  15. 75 FR 32490 - Issues in the Development of Medical Products for the Prophylaxis and/or Treatment of Acute...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... treatment of acute AMR in kidney transplant recipients, including clinical trial design and endpoints. The... acute AMR Endpoints to be evaluated to assess outcome Outcomes achieved with currently used...

  16. Minocycline upregulates cyclic AMP response element binding protein and brain-derived neurotrophic factor in the hippocampus of cerebral ischemia rats and improves behavioral deficits

    PubMed Central

    Zhao, Yu; Xiao, Ming; He, Wenbo; Cai, Zhiyou

    2015-01-01

    Background and purpose The cAMP response element binding protein (CREB) plays an important role in the mechanism of cognitive impairment and is also pivotal in the switch from short-term to long-term memory. Brain-derived neurotrophic factor (BDNF) seems a promising avenue in the treatment of cerebral ischemia injury since this neurotrophin could stimulate structural plasticity and repair cognitive impairment. Several findings have displayed that the dysregulation of the CREB–BDNF cascade has been involved in cognitive impairment. The aim of this study was to investigate the effect of cerebral ischemia on learning and memory as well as on the levels of CREB, phosphorylated CREB (pCREB), and BDNF, and to determine the effect of minocycline on CREB, pCREB, BDNF, and behavioral functional recovery after cerebral ischemia. Methods The animal model was established by permanent bilateral occlusion of both common carotid arteries. Behavior was evaluated 5 days before decapitation with Morris water maze and open-field task. Four days after permanent bilateral occlusion of both common carotid arteries, minocycline was administered by douche via the stomach for 4 weeks. CREB and pCREB were examined by Western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry. BDNF was measured by immunohistochemistry and Western blotting. Results The model rats after minocycline treatment swam shorter distances than control rats before finding the platform (P=0.0007). The number of times the platform position was crossed for sham-operation rats was more than that of the model groups in the corresponding platform location (P=0.0021). The number of times the platform position was crossed for minocycline treatment animals was significantly increased compared to the model groups in the corresponding platform position (P=0.0016). CREB, pCREB, and BDNF were downregulated after permanent bilateral occlusion of both common carotid arteries in the model group

  17. Drug repurposing for immune modulation in acute ischemic stroke.

    PubMed

    Amantea, Diana; Bagetta, Giacinto

    2016-02-01

    Innate immune cells play a dualistic role in the evolution of ischemic brain damage, with classic phenotypes promoting injury, and alternatively activated M2 microglia/macrophages or N2 neutrophils providing tissue remodelling and repair. Recently, a number of drugs commonly used for other indications (i.e., azithromycin, minocycline, bexarotene, rosiglitazone, metformin) was reported to provide neuroprotection in preclinical stroke models by promoting immune polarization towards non-inflammatory, protective phenotypes. Repurposing drugs with a well-established safety profile should allow a reduction in the risk of clinical trial failure that has dominated the unsuccessful development of neuroprotective drugs in stroke during the last decades. The clinical validation of the proof of concept, followed by the assessment of safety and efficacy of immune-polarizing repurposed drugs will definitively offer new opportunities for the acute treatment of ischemic stroke. PMID:26657075

  18. [Acute respiratory distress syndrome: definitions, mechanisms and treatment].

    PubMed

    Urso, Domenico Lorenzo

    2006-01-01

    Acute respiratory distress syndrome is a secondary acute respiratory insufficiency caused by an inflammatory syndrome which is characterized by an increased of permeability pulmonary edema, associated with many other clinic anomalies, radiological and pathophysiological not directly caused by, but with which it could coexist, a left atrial hypertension. The illness, characterized by refractory hypoxemia, recognizes several causes, which have direct or indirect harm on the cells of the membrane alveolus-capillary. In spite of the improvements in the therapeutic approach, during these last 40 years, represented by the aid of the mechanical ventilation and the use of selective pulmonary vasodilators, this condition is life threatening and often lethal: 90% of mortality rate amongst those older than 65 years. PMID:16913178

  19. Hepatitis C and recurrent treatment-resistant acute ischemic stroke

    PubMed Central

    Tarsia, Joseph; Dunn, Casey; Aysenne, Aimee; Shah, Basil; Moore, David F.

    2013-01-01

    Since the introduction of recombinant tissue plasminogen activator and thrombolysis, acute ischemic stroke has become a treatable disorder if the patient presents within the 4.5-hour time window. Typically, sporadic stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated with atrial fibrillation. In the over-65-year age group, more rare causes of stroke, such as antiphospholipid syndromes, are unusual; such stroke etiologies are mostly seen in a younger age group (<55 years). Here we describe acute ischemic stroke in three patients >65 years with hepatitis C–associated antiphospholipid antibodies. We suggest that screening for antiphospholipid disorders in the older patient might be warranted, with potential implications for therapeutic management and secondary stroke prevention. PMID:23543984

  20. Hybrid Treatment of Acute Abdominal Aortic Thrombosis Presenting with Paraplegia.

    PubMed

    Azzarone, Matteo; De Troia, Alessandro; Iazzolino, Luigi; Nabulsi, Bilal; Tecchio, Tiziano

    2016-05-01

    Acute thrombotic or embolic occlusion of the abdominal aorta is a rare vascular emergency associated with high morbidity and mortality rates. Classically, the clinical presentation is a severe peripheral ischemia with bilateral leg pain as the predominant feature. Aortic occlusion presenting as an isolated acute onset of paraplegia due to spinal cord ischemia is very rare and requires improved awareness to prevent adverse outcomes associated with delayed diagnosis. We report the case of a 54-year-old man who presented with sudden paraplegia due to the thrombotic occlusion of the infrarenal aorta involving the first segment of the common iliac arteries on both sides; emergent transperitoneal aorto iliac thrombectomy combined with the endovascular iliac kissing-stent technique were performed achieving perioperative complete regression of the symptoms. PMID:26968371

  1. [Invasive diagnosis, transcatheter and surgical treatment of acute coronary syndromes].

    PubMed

    Fabián, J; Hricák, V; Fridrich, V; Fischer, V

    1998-01-01

    On the basis of long-term personal experiences and critical evaluation of the present literatury sources authors described the role of invasive diagnostic methods and transcathetral and cardiosurgical possibilities in the recognition and therapy of acute coronary syndromes. These techniques are, and in the forthcoming year shall be available only in specialized institutions. The paper describes the indication for these aggressive techniques as well as their limitations and complications. The goal of the presented article is to inform both the cardiological and frequently broad physicians' societies about the possibilities of diaventional cardiology and cardiosurgery which will be gradually more applied in the care of the patients with acute coronary syndromes. (Ref. 39, Tab. 2, Fig. 3.) PMID:9919748

  2. Arthroscopic treatment of acute and chronic acromioclavicular joint dislocation.

    PubMed

    Lafosse, Laurent; Baier, Gloria P; Leuzinger, Jan

    2005-08-01

    This article presents an all-arthroscopic technique for coracoclavicular ligament reconstruction by ligamentoplasty after acute or chronic acromioclavicular joint dislocation. A coracoacromial ligament transfer is done to reconstruct the torn coracoclavicular ligaments, similar to open surgery. The coracoacromial ligament is dissected from the undersurface of the acromion and is reinserted on the inferior clavicle by transosseous suture fixation. Additional wire or screw stabilization may be used. With this method, we achieve a very satisfactory reduction of the dislocated acromioclavicular joint. PMID:16086572

  3. Holmium:YAG laser angioplasty: treatment of acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Topaz, On

    1993-06-01

    We report our clinical experience with a group of 14 patients who presented with acute myocardial infarction. A holmium:YAG laser was applied to the infarct-related artery. This laser emits 250 - 600 mJ per pulse, with a pulse length of 250 microseconds and repetition rate of 5 Hz. Potential benefits of acute thrombolysis by lasers include the absence of systemic lytic state; a shortened thrombus clearing time relative to using thrombolytics; safe removal of the intracoronary thrombus and facilitation of adjunct balloon angioplasty. Potential clinical difficulties include targeting the obstructive clot and plaque, creation of debris and distal emboli and laser-tissue damage. It is conceivable that holmium:YAG laser can be a successful thrombolytic device as its wave length (2.1 microns) coincides with strong water absorption peaks. Since it is common to find an atherosclerotic plaque located under or distal to the thrombotic occlusion, this laser can also be applied for plaque ablation, and the patient presenting with acute myocardial infarction can clearly benefit from the combined function of this laser system.

  4. Oral Ambulatory Treatment of Acute Osteomyelitis in Children: A Case-Control Study.

    PubMed

    Roul-Levy, Antoine; Looten, Vincent; Bachy, Manon; Grimprel, Emmanuel; Carbajal, Ricardo; Vialle, Raphaël

    2016-03-01

    The treatment of acute hematogenous osteomyelitis has evolved in recent years to a shorter parenteral treatment with an early switch to the oral route. Current publications recommend a 2- to 4-day parenteral treatment before the oral switch. We retrospectively analyzed a series of 45 children aged 1 to 11 years and treated in our department for acute osteomyelitis without severity criterion. Nineteen of 45 patients were treated by an exclusive ambulatory oral treatment by amoxicillin and clavulanic acid. Twenty six of 45 patients had a 2- to 4-day parenteral treatment before the oral switch. The minimum follow-up was 6 months. The primary endpoint was a clinical, radiographic, and biologic healing, 6 months after the beginning of the treatment. The secondary endpoints evaluated were the length of hospitalization, the total duration of treatment, and the type of antibiotic used. On the primary endpoint, we did not find any significant difference between the 2 treatments (P = 0.38). On the duration of treatment, we found a significant difference (P = 0.049) in favor of oral treatment. The ambulatory oral treatment by amoxicillin and clavulanic acid seems to be a valid alternative to the classical parenteral then oral sequence in the treatment of acute hematogenous osteomyelitis in children without severity criterion. PMID:26928094

  5. The Evolution and Current Utility of Esophageal Stent Placement for the Treatment of Acute Esophageal Perforation.

    PubMed

    Herrera, Argenis; Freeman, Richard K

    2016-08-01

    Esophageal stent placement was used primarily for the treatment of malignant strictures until the development of a new generation of biomaterials allowed the production of easily removable, occlusive stents in 2001. Since then, thoracic surgeons have gained experience using esophageal stents for the treatment of acute esophageal perforation. As part of a hybrid treatment strategy, including surgical drainage of infected spaces, enteral nutrition, and aggressive supportive care, esophageal stent placement has produced results that can exceed those of traditional surgical repair. This review summarizes the evolution of esophageal stent use for acute perforation and provides evidence-based recommendations for the technique. PMID:27427525

  6. [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. PMID:27211353

  7. High Feasibility of Empiric HIV Treatment for Patients With Suspected Acute HIV in an Emergency Department.

    PubMed

    Jacobson, Kathleen R; Arora, Sanjay; Walsh, Kristin B; Lora, Meredith; Merjavy, Stephen; Livermore, Shanna; Menchine, Michael

    2016-07-01

    Earlier intervention in acute HIV infection limits HIV reservoirs and may decrease HIV transmission. We developed criteria for empiric antiretroviral therapy (ART) in an emergency department (ED) routine HIV screening program. We assessed the feasibility and willingness of patients with suspected acute HIV infection in the ED to begin ART. A suspected acute HIV infection was defined as a positive HIV antigen antibody combination immunoassay with pending HIV-antibody differentiation test results and HIV RNA viral load. During the study period, there were 16 confirmed cases of acute HIV infection: 11 met our criteria for empiric ART and agreed to treatment, 10 were prescribed ART, and 1 left the ED against medical advice without a prescription for ART. Eight patients completed at least one follow-up visit. Empiric HIV treatment in an ED is feasible, well received by patients, and offers a unique entry point into the HIV care continuum. PMID:27028498

  8. Predictors and Moderators of Acute Outcome in the Treatment for Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    Curry, John; Rohde, Paul; Simons, Anne; Silva, Susan; Vitiello, Benedetto; Kratochvil, Christopher; Reinecke, Mark; Feeny, Norah; Wells, Karen; Pathak, Sanjeev; Weller, Elizabeth; Rosenberg, David; Kennard, Betsy; Robins, Michele; Ginsburg, Golda; March, John

    2006-01-01

    Objective: To identify predictors and moderators of response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive-behavioral therapy (CBT), both fluoxetine and CBT, or clinical management with pill placebo in the Treatment for Adolescents With Depression Study (TADS). Method: Potential baseline…

  9. Clofarabine for the treatment of adult acute lymphoid leukemia: the Group for Research on Adult Acute Lymphoblastic Leukemia intergroup.

    PubMed

    Huguet, Françoise; Leguay, Thibaut; Raffoux, Emmanuel; Rousselot, Philippe; Vey, Norbert; Pigneux, Arnaud; Ifrah, Norbert; Dombret, Hervé

    2015-04-01

    Clofarabine, a second-generation purine analog displaying potent inhibition of DNA synthesis and favorable pharmacologic profile, is approved for the treatment of acute lymphoblastic leukemia (ALL) after failure of at least two previous regimens in patients up to 21 years of age at diagnosis. Good neurologic tolerance, synergy with alkylating agents, management guidelines defined through pediatric ALL and adult acute myeloid leukemia, have also prompted its administration in more than 100 adults with Philadelphia chromosome-positive and negative B lineage and T lineage ALL, as single agent (40 mg/m(2)/ day for 5 days), or in combination. In a Group for Research on Adult Acute Lympho- blastic Leukemia (GRAALL) retrospective study of two regimens (clofarabine ± cyclophosphamide + / - etoposide (ENDEVOL) ± mitoxantrone ± asparaginase ± dexamethasone (VANDEVOL)), remission was achieved in 50% of 55 relapsed/refractory patients, and 17-35% could proceed to allogeneic stem cell. Clofarabine warrants further exploration in advanced ALL treatment and bridge-to-transplant. PMID:24996442

  10. 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

  11. Minocycline, a microglial inhibitor, reduces ‘honey trap’ risk in human economic exchange

    PubMed Central

    Watabe, Motoki; Kato, Takahiro A.; Tsuboi, Sho; Ishikawa, Katsuhiko; Hashiya, Kazuhide; Monji, Akira; Utsumi, Hideo; Kanba, Shigenobu

    2013-01-01

    Recently, minocycline, a tetracycline antibiotic, has been reported to improve symptoms of psychiatric disorders and to facilitate sober decision-making in healthy human subjects. Here we show that minocycline also reduces the risk of the ‘honey trap’ during an economic exchange. Males tend to cooperate with physically attractive females without careful evaluation of their trustworthiness, resulting in betrayal by the female. In this experiment, healthy male participants made risky choices (whether or not to trust female partners, identified only by photograph, who had decided in advance to exploit the male participants). The results show that trusting behaviour in male participants significantly increased in relation to the perceived attractiveness of the female partner, but that attractiveness did not impact trusting behaviour in the minocycline group. Animal studies have shown that minocycline inhibits microglial activities. Therefore, this minocycline effect may shed new light on the unknown roles microglia play in human mental activities. PMID:23595250

  12. NUTRITIONAL THERAPY IN THE TREATMENT OF ACUTE CORROSIVE INTOXICATION IN ADULTS

    PubMed Central

    Chibishev, Andon; Markoski, Velo; Smokovski, Ivica; Shikole, Emilija; Stevcevska, Aleksandra

    2016-01-01

    Introduction: Acute intoxications with corrosive substances can cause severe chemical injuries of the upper gastrointestinal tract, most often located in the mouth, pharynx, esophagus, stomach and duodenum. If a patient survives the acute phase of intoxication, regenerative response may result in esophageal and/or gastric stenosis, and increased risk of esophageal and gastric cancer. Such intoxication may be fatal due to perforation or tracheal necrosis. Enteral nutrition is a nutritional method when nutritional substances are administered through specially designed tubing placed through the nose or percutaneously, directly into the GIT. Aim: The aim of this study is to describe the methods of artificial nutrition in patients with acute corrosive intoxications and the importance of nutritional support in the treatment of these intoxications. Discussion: Nutrition in the treatment of acute corrosive intoxications is one of the most important therapeutic processes that largely contribute to faster recovery of the post-corrosive injuries of upper GIT, stabilization of biologic, immunologic and metabolic parameters, and reduction of length of stay in hospital Aim of the treatment of acute corrosive intoxications is to prevent perforation and progressive fibrosis, and esophageal and gastric stenosis. There are different and often conflicting positions, on the conservative treatment of acute corrosive intoxications in adults. Such treatment mainly consists of anti-secretory treatment, antibiotics and intensive hyper-alimentation, aiming to prevent late post-corrosive intoxications. Conclusion: It is considered that nutritional support plays a major role in maintenance of metabolic processes and prevention of severe metabolic complications that could additionally aggravate the condition and impair the treatment. PMID:27047272

  13. Minocycline mitigates the gliogenic effects of proinflammatory cytokines on neural stem cells.

    PubMed

    Vay, Sabine Ulrike; Blaschke, Stefan; Klein, Rebecca; Fink, Gereon Rudolf; Schroeter, Michael; Rueger, Maria Adele

    2016-02-01

    Mobilizing endogenous neural stem cells (NSCs) in the adult brain is designed to enhance the brain's regenerative capacity after cerebral lesions, e.g., as a result of stroke. Cerebral ischemia elicits neuroinflammatory processes affecting NSCs in multiple ways, the precise mechanisms of which currently remain elusive. An inhibitory effect of minocycline on microglia activation, a hallmark of postischemic neuroinflammation, has already been demonstrated in clinical trials, showing minocycline to be safe and potentially effective in ischemic stroke. Here we investigate the direct effects of minocycline and of proinflammatory cytokines on the differentiation potential of NSCs in vitro and in vivo. Primary fetal rat NSCs were treated with minocycline plus a combination of the proinflammatory cytokines tumor necrosis factor-α, interleukin 1β, and interleukin 6. The differentiation fate of NSCs was assessed immunocytochemically. To investigate the effects of minocycline and inflammation in vivo, minocycline or lipopolysaccharides were injected intraperitoneally into adult rats, with subsequent immunohistochemistry. Minocycline alone did not affect the differentiation potential of NSCs in vivo or in vitro. In contrast, proinflammatory cytokines accelerated the differentiation of NSCs, promoting an astrocytic fate while inhibiting neurogenesis in vitro and in vivo. It is interesting to note that minocycline counteracted this cytokine-induced rapid astrocytic differentiation and restored the neurogenic and oligodendrogliogenic potential of NSCs. Data suggest that minocycline antagonizes the rapid glial differentiation induced by proinflammatory cytokines following cerebral ischemia but without having a direct effect on the differentiation potential of NSCs. Thus, minocycline constitutes a promising drug for stroke research, counteracting the detrimental effects of postischemic neuroinflammation in multiple ways. PMID:26525774

  14. 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.

  15. 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

  16. Successful treatment of pegaspargase-induced acute hepatotoxicity with vitamin B complex and L-carnitine

    PubMed Central

    Karur, Vinit; Herrington, Jon D.; Walker, Mary G.

    2016-01-01

    Pegaspargase is a chemotherapy drug used in the treatment of acute lymphoblastic leukemia (ALL). One of the adverse effects of pegaspargase is hepatotoxicity, which can rapidly lead to liver failure and death. We report a patient with ALL who developed pegaspargase-induced severe hepatotoxicity that was rescued by treatment with vitamin B complex and L-carnitine. Our patient had a quicker response than prior reported cases, suggesting this treatment might be a better regimen. PMID:26722167

  17. Treatment of compartment syndrome of the thigh associated with acute renal failure after the Wenchuan earthquake.

    PubMed

    Duan, Xin; Zhang, Kaiwei; Zhong, Gang; Cen, Shiqiang; Huang, Fuguo; Lv, Jingtong; Xiang, Zhou

    2012-04-01

    Compartment syndrome of the thigh is a rare emergency often treated operatively. The purpose of this study was to evaluate the effects of nonoperative treatment for compartment syndrome of the thigh associated with acute renal failure after the 2008 Wenchuan earthquake. Nonoperative treatment, which primarily involves continuous renal replacement therapy, was performed in 6 patients (3 men and 3 women) who presented with compartment syndrome of the thigh associated with acute renal failure. The mean mangled extremity severity score (MESS) and laboratory data regarding renal function were analyzed before and after treatment, and the clinical outcome was evaluated at 17-month follow-up. Laboratory data regarding renal function showed improvements. All 6 patients survived with the affected lower limbs intact after nonoperative treatment. Follow-up revealed active knee range of motion and increased muscle strength, as well as a recovery of sensation. A positive linear correlation was found between MESS and the time required to achieve a reduction in swelling, as well as the time required for the recovery of sensation and knee range of motion (r>0.8; P<.05). Satisfactory clinical outcomes were obtained in patients with compartment syndrome of the thigh associated with acute renal failure.Urine alkalization, electrolyte and water balance, and continuous renal replacement therapy have played an important role in saving lives and extremities. Nonoperative treatment should be considered in the treatment of compartment syndrome of the thigh associated with acute renal failure. PMID:22495847

  18. 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. PMID:27299279

  19. Psychosocial Acute Treatment in Early-Episode Schizophrenia Disorders

    ERIC Educational Resources Information Center

    Bola, John R.

    2006-01-01

    Objective: This article reviews evidence on the treatment of early episode schizophrenia spectrum disorders that contradicts, in some cases, the American Psychiatric Association's generic recommendation of antipsychotic medication treatment for at least a year. Method: Evidence on lack of diagnostic validity, absence of demonstrated long-term…

  20. Endovascular treatment of nonvariceal acute arterial upper gastrointestinal bleeding

    PubMed Central

    Andersen, Poul Erik; Duvnjak, Stevo

    2010-01-01

    Transcatheter arterial embolization as treatment of upper nonvariceal gastrointestinal bleeding is increasingly being used after failed primary endoscopic treatment. The results after embolization have become better and surgery still has a high mortality. Embolization is a safe and effective procedure, but its use is has been limited because of relatively high rates of rebleeding and high mortality, both of which are associated with gastrointestinal bleeding and non-gastrointestinal related mortality causes. Transcatheter arterial embolization is a valuable minimal invasive method in the treatment of early rebleeding and does not involve a high risk of treatment associated complications. A multidisciplinary approach is necessary in the treatment of these patients and should comprise gastroenterologists, interventional radiologists, anaesthesiologists, and surgeons to achieve the best possible results. PMID:21160665

  1. Results of treatment with an intensive combination induction regimen containing idarubicin in children with acute myeloblastic leukemia: preliminary report of the Argentine Group for Treatment of Acute Leukemia.

    PubMed

    Sackmann-Muriel, F; Fernández-Barbieri, M A; Santarelli, M T; Matus-Ridley, M; Rosso, A; Negri-Aranguren, P; Cerutti, I; Gomel, M; Kvicala, R

    1993-12-01

    In April 1990, the Argentine Group for Treatment of Acute Leukemia began a multicenter trial for the treatment of previously untreated acute myeloblastic leukemia patients who were under 21 years of age. Initial treatment consisted of an 8-day induction phase with cytarabine together with idarubicin on days 3 to 5 and etoposide on days 6 to 8. A multidrug consolidation phase was subsequently administered and, after a treatment-free interval of 2 to 4 weeks, two 5-day intensification courses with high-dose cytarabine and etoposide were delivered with a 4-week interval between each course. Continuation therapy was started 2 to 4 weeks after the second course, with 6-thioguanine daily and cytarabine daily for 4 days every 4 weeks. Treatment was stopped after 18 months in children in continuous complete remission. A preliminary evaluation of this ongoing study included 36 patients with a mean age of 7.5 years (age range, 5 months to 16 years). The majority of patients had a French-American-British classification of M2 (n = 13) or M4 (n = 8). Complete remission was achieved by 91.7% of patients, while one died from sepsis in bone marrow hypoplasia and two were regarded as treatment failures. At a median follow-up of 12 months (range, 2 to 23 months) there were 12 adverse events: six bone marrow relapses, one bone marrow/skin relapse, and five deaths in complete remission (all deaths occurred during the consolidation phase). During the induction phase most of the patients experienced prolonged myelosuppression, and grade 3 to 4 toxicity (according to the Children's Cancer Group criteria) was frequently seen. Alopecia was universal. However, toxicity was manageable. We conclude that idarubicin in combination with cytarabine and etoposide is a highly effective regimen for induction in children with acute myeloblastic leukemia. PMID:8290970

  2. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    PubMed Central

    Jacob, Joe Antony; Salmani, Jumah Masoud Mohammad; Chen, Baoan

    2016-01-01

    Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration. This review focuses on the drugs under preclinical and clinical study in the ongoing efforts for treatment of acute and chronic lymphoblastic leukemia. PMID:27382259

  3. Synthesis of a novel photopolymerized nanocomposite hydrogel for the treatment of acute mechanical damage to cartilage

    NASA Astrophysics Data System (ADS)

    Schlichting, Kathryn; Copeland-Johnson, Trishelle; Goodman, Matthew; Lipert, Robert; McKinley, Todd; Martin, James; Mallapragada, Surya; Lin, Zhiqun

    2011-03-01

    Posttraumatic osteoarthritis is caused by a cascade of pathobiologic and pathomechanical events starting with intraarticular fractures in the cartilage. Currently, treatment of fractures is completely focused on restoration of the macroanatomy of the joint. The premise is that restoring the macroanatomy will prevent ongoing stresses and in turn prevent cartilage degeneration. However, current treatment ignores acute mechanical damage sustained by cartilage at the time of injury. This study describes the initial development of a novel nanocomposite photopolymerizing copolymer that has potential to restore local structural integrity to acutely injured cartilage, and subsequently act as a carrier for chondrocyte-enhancing bioactive agents.

  4. A new approach to treatment of acute heart failure.

    PubMed

    Goldsmith, Steven R

    2016-05-01

    Conventional therapies for acute decongestion have yielded uniformly poor results in patients with acute heart failure (AHF). The failure of current strategies may be due to advanced disease in hospitalized patients, incomplete therapy, inherent limitations to existing therapy, or some combination of all three factors. Loop diuretics are the mainstay of current therapy and are in theory not ideal since while producing immediate intravascular volume reduction and relief of symptoms they activate neurohormonal forces that are deleterious to both the heart and the kidney. Ultrafiltration is an alternative to loop diuretics but has not proved advantageous in the setting of renal dysfunction, and if not carefully applied may also aggravate neurohormonal imbalance. In theory decongestive therapy for AHF should remove large volumes of fluid quickly and safely and improve symptoms, particularly dyspnea, without aggravating renal dysfunction or causing neurohormonal activation. Several studies have now suggested that the use of aquaretics such as antagonists to the V2 receptor for arginine vasopressin may be useful as adjunctive therapy in AHF, particularly when renal dysfunction and/or hyponatremia are present. These agents leverage osmotic forces to produce tissue decongestion while causing a water diuresis. They do not adversely affect renal function or neurohormonal balance. Building on the current base of knowledge about outcomes in AHF together with the only study of vasopressin antagonists as short-term monotherapy in chronic heart failure, it would be reasonable to design a trial in AHF in which the use of loop diuretics was minimized in favor of these agents. PMID:26946929

  5. Treatment advances have not improved the early death rate in acute promyelocytic leukemia

    PubMed Central

    McClellan, James Scott; Kohrt, Holbrook E.; Coutre, Steven; Gotlib, Jason R.; Majeti, Ravindra; Alizadeh, Ash A.; Medeiros, Bruno C.

    2012-01-01

    Early mortality in acute promyelocytic leukemia has been reported to occur in less than 10% of patients treated in clinical trials. This study reports the incidence and clinical features of acute promyelocytic leukemia patients treated at Stanford Hospital, CA, USA since March 1997, focusing on early mortality. We show that the risk of early death in acute promyelocytic leukemia patients is higher than previously reported. In a cohort of 70 patients who received induction therapy at Stanford Hospital, 19% and 26% died within seven and 30 days of admission, respectively. High early mortality was not limited to our institution as evaluation of the Surveillance, Epidemiology and End Results Database demonstrated that 30-day mortality for acute promyelocytic leukemia averaged 20% from 1977–2007 and did not improve significantly over this interval. Our findings show that early death is now the greatest contributor to treatment failure in this otherwise highly curable form of leukemia. PMID:21993679

  6. Pharmacotherpy and Alzheimer's Disease: The M-Drugs (Melatonin, Minocycline, Modafinil, and Memantine) Approach.

    PubMed

    Daulatzai, Mak Adam

    2016-01-01

    Despite advances in understanding the pathophysiology of Alzheimer's disease (AD), its therapy remains largely symptomatic and supportive. Acetylcholinesterase inhibitors - the first-line drugs used today do not prevent and treat AD. So far, over 90 Phase 3 trials of AD have been unsuccessful with 99.0% failure rate. There is, therefore, an urgent need to find effective new therapies for AD. Owing to the multifactorial nature of AD pathogenesis, polypharmacy with drugs that target heterogeneous pathophysiological pathways, needs to be considered. Fortunately, several drugs used currently in clinical use as monotherapies can be exploited in AD. This article, therefore, presents a novel pharmacological treatment paradigm and recommends the use of valuable diseasemodifying approved drugs, viz. melatonin, minocycline, modafinil, and memantine (the "M" Drugs). Melatonin - a neuroprotector is an antioxidant and anti-inflammatory. Minocycline is also neuroprotective, it reduces neuroinflammation and CNS pathology and prevents cell death. Sleep deprivation leads to decreased hippocampal neurogenesis, increased amyloid beta generation, and causes memory dysfunction. Modafinil - a wake-promoting agent is approved for use in narcolepsy and obstructive sleep apnea. It improves global mental status, hippocampal neurogenesis, attention, and cognition. Memantine is an uncompetitive N-methyl-d-aspartic acid receptor antagonist and is approved for the management of moderate-to-severe AD. The paramount possible beneficial effects of the M-drugs may include significant memory and cognitive enhancement in aging, mild cognitive impairment, and AD. The M drugs-centric pharmacotherapy strategy is comprehensive and pragmatic and is meant to combat multiple pathological targets and ameliorate cognitive dysfunction/AD. PMID:26845126

  7. Early treatment of acute migraine: new evidence of benefits.

    PubMed

    Valade, D

    2009-12-01

    The current management approach to migraine headaches advocates use of triptan medications early in the course of an attack while pain is still mild, rather than waiting to treat the pain when it has progressed to moderate-severe. Recently, strong new evidence for the benefits of early intervention has become available. The AEGIS, AIMS and AwM studies of almotriptan in patients with migraine indicate that earlier treatment initiation and lower pain intensity at the time of treatment are important predictors of enhanced therapeutic outcomes. The opportunity to treat early exists for about 50% of all migraine attacks, which offers considerable scope for improving migraine management. Importantly, treating pain early and before it has progressed beyond 'mild' meets many of the expectations patients have of their migraine treatment. It is believed that consistent, positive outcomes may assist in overcoming the various physician- and patient-perceived barriers to adoption of this beneficial treatment strategy. PMID:20017750

  8. Magnetic resonance diffusion tensor imaging following major ozonated autohemotherapy for treatment of acute cerebral infarction

    PubMed Central

    Wu, Xiao-na; Zhang, Tao; Wang, Jun; Liu, Xiao-yan; Li, Zhen-sheng; Xiang, Wei; Du, Wei-qing; Yang, Hong-jun; Xiong, Tie-gen; Deng, Wen-ting; Peng, Kai-run; Pan, Su-yue

    2016-01-01

    Major ozonated autohemotherapy has been shown to promote recovery of upper limb motor function in patients with acute cerebral infarction, but whether major ozonated autohemotherapy affects remote injury remains poorly understood. Here, we assumed that major ozonated autohemotherapy contributes to recovery of clinical function, possibly by reducing remote injury after acute cerebral infarction. Sixty acute cerebral infarction patients aged 30–80 years were equally and randomly allocated to ozone treatment and control groups. Patients in the ozone treatment group received medical treatment and major ozonated autohemotherapy (47 mg/L, 100 mL ozone) for 10 ± 2 days. Patients in the control group received medical treatment only. National Institutes of Health Stroke Scale score, modified Rankin scale score, and reduced degree of fractional anisotropy values of brain magnetic resonance diffusion tensor imaging were remarkably decreased, brain function improved, clinical efficiency significantly increased, and no obvious adverse reactions detected in the ozone treatment group compared with the control group. These findings suggest that major ozonated autohemotherapy promotes recovery of neurological function in acute cerebral infarction patients by reducing remote injury, and additionally, exhibits high safety.

  9. Ecallantide: a plasma kallikrein inhibitor for the treatment of acute attacks of hereditary angioedema.

    PubMed

    Stolz, L E; Horn, P T

    2010-08-01

    Hereditary angioedema (HAE) is a debilitating, potentially fatal disease characterized by variable and unpredictable acute attacks of swelling affecting the subcutaneous tissue and mucosa. It is an autosomal dominant disorder resulting from a genetic deficiency of functional C1-esterase inhibitor. Available treatments include long-term prophylaxis, short-term prophylaxis and treatment of acute attacks. Ecallantide is a novel, specific and potent inhibitor of plasma kallikrein that was recently approved in the United States for the treatment of acute attacks of HAE in patients aged 16 years and older. In two phase III clinical trials, the subcutaneous administration of 30 mg ecallantide resulted in significantly greater symptom improvement than placebo for acute attacks of HAE. Ecallantide was generally well tolerated throughout the clinical development program. The main safety concern following ecallantide treatment is hypersensitivity reactions, including anaphylaxis. A Risk Evaluation and Management Strategy (REMS) has been implemented to minimize this risk and a long-term observational safety study is currently under way to collect more information about hypersensitivity and immunogenicity. Ecallantide represents a novel treatment option for patients with HAE. PMID:20830315

  10. Arthroscopically Assisted Treatment of Acute Dislocations of the Acromioclavicular Joint

    PubMed Central

    Braun, Sepp; Beitzel, Knut; Buchmann, Stefan; Imhoff, Andreas B.

    2015-01-01

    Arthroscopically assisted treatments for dislocations of the acromioclavicular joint combine the advantages of exact and visually controlled coracoid tunnel placement with the possibility of simultaneous treatment of concomitant injuries. The clinical results of previous arthroscopically assisted techniques have been favorable at midterm and long-term follow-up. The presented surgical technique combines the advantages of arthroscopically positioned coracoclavicular stabilization with an additional suture cord cerclage of the acromioclavicular joint capsule for improved horizontal stability. PMID:26870646

  11. Acute severe asthma: new approaches to assessment and treatment.

    PubMed

    Papiris, Spyros A; Manali, Effrosyni D; Kolilekas, Likurgos; Triantafillidou, Christina; Tsangaris, Iraklis

    2009-01-01

    The precise definition of a severe asthmatic exacerbation is an issue that presents difficulties. The term 'status asthmaticus' relates severity to outcome and has been used to define a severe asthmatic exacerbation that does not respond to and/or perilously delays the repetitive or continuous administration of short-acting inhaled beta(2)-adrenergic receptor agonists (SABA) in the emergency setting. However, a number of limitations exist concerning the quantification of unresponsiveness. Therefore, the term 'acute severe asthma' is widely used, relating severity mostly to a combination of the presenting signs and symptoms and the severity of the cardiorespiratory abnormalities observed, although it is well known that presentation does not foretell outcome. In an acute severe asthma episode, close observation plus aggressive administration of bronchodilators (SABAs plus ipratropium bromide via a nebulizer driven by oxygen) and oral or intravenous corticosteroids are necessary to arrest the progression to severe hypercapnic respiratory failure leading to a decrease in consciousness that requires intensive care unit (ICU) admission and, eventually, ventilatory support. Adjunctive therapies (intravenous magnesium sulfate and/or others) should be considered in order to avoid intubation. Management after admission to the hospital ward because of an incomplete response is similar. The decision to intubate is essentially based on clinical judgement. Although cardiac or respiratory arrest represents an absolute indication for intubation, the usual picture is that of a conscious patient struggling to breathe. Factors associated with the increased likelihood of intubation include exhaustion and fatigue despite maximal therapy, deteriorating mental status, refractory hypoxaemia, increasing hypercapnia, haemodynamic instability and impending coma or apnoea. To intubate, sedation is indicated in order to improve comfort, safety and patient-ventilator synchrony, while at the

  12. Minocycline-induced polyarteritis nodosa-like vasculitis presenting as brainstem stroke.

    PubMed

    Klaas, James P; Matzke, Thomas; Makol, Ashima; Fulgham, Jimmy R

    2015-05-01

    Minocycline use has been associated with the development of autoimmune disorders, including drug-induced vasculitis. Previously published reports suggest that clinical manifestations are limited to cutaneous, constitutional, or musculoskeletal symptoms. To our knowledge there has been only one reported patient with ischemic stroke in the setting of minocycline-induced vasculitis. We describe a 26-year-old woman, with no vascular risk factors, who had an ischemic pontine stroke in the setting of biopsy-proven minocycline-induced polyarteritis nodosa-like vasculitis. Discontinuation of minocycline resulted in resolution of the vasculitis, and she has not had any recurrent ischemic events. This report shows that ischemic strokes may occur as a result of minocycline-induced vasculitis. While this is likely a rare association, recognition is important given the widespread use of minocycline and the potential for devastating consequences in a young population. Consequently, drug-induced vasculitis should be considered in patients with an ischemic stroke taking minocycline. PMID:25778384

  13. [Current approaches to the treatment of severe hypoxic respiratory insufficiency (acute lung injury; acute respiratory distress syndrome)].

    PubMed

    Kluge, S; Müller, T; Pfeifer, M

    2011-02-01

    Lung-protective ventilation with a low tidal volume, plateau pressure < 30 cm H(2)O. oxygen saturation > 90% and permissive hypercapnia results in reduction of the mortality rate in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The level of the positive end-expiratory pressure (PEEP) must be chosen in relation to oxygen requirement. High frequency oscillatory ventilation and neurally adjusted ventilatory assist are promising methods. However, further studies with firm end-points have to be awaited before a final judgment is possible. Veno-venous extracorporeal membrane oxygenation (ECMO) can ensure life-sustaining gas exchange in patients with severe vitally compromised pulmonary failure, to provide time for lung tissue to heal and reduce ventilatory stress. The latest guidelines for analgesia and sedation in intensive care medicine demand consistent monitoring of the level of sedation and the intensity of pain. The sedation should be interrupted daily, with phases of awakenings and, if possible, spontaneous breathing. Methods of supportive treatment: Positional treatment (prone position) and inhalation of vasodilators can improve ventilation/perfusion mismatch and thus oxygenation. However, administration of surfactant is currently not advised in adult respiratory failure. PMID:21271478

  14. Recent advances in the treatment of colonic diverticular disease and prevention of acute diverticulitis.

    PubMed

    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

  15. 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

  16. Current standard treatment of adult acute promyelocytic leukaemia.

    PubMed

    Lo-Coco, Francesco; Cicconi, Laura; Breccia, Massimo

    2016-03-01

    The outcome of patients with acute promyelocytic leukaemia (APL) has dramatically improved over the last two decades, due to the introduction of combined all-trans retinoic acid (ATRA) and chemotherapy regimens and, more recently, to the advent of arsenic trioxide (ATO). ATRA and anthracycline-based chemotherapy remains a widely used strategy, providing cure rates above 80%, but it is associated with risk of severe infections and occurrence of secondary leukaemias. ATO is the most effective single agent in APL and, used alone or in combination with ATRA or ATRA and reduced-intensity chemotherapy, results in greater efficacy with considerably less haematological toxicity. The toxic profile of ATO includes frequent, but manageable, QTc prolongation and increase of liver enzymes. Two large randomized studies have shown that ATRA + ATO is superior to ATRA + chemotherapy for newly diagnosed low-risk APL resulting in 2-4 year event-free survival rates above 90% and very few relapses. According to real world data, the spectacular progress in APL outcomes reported in clinical trials has not been paralleled by a significant improvement in early death rates, this remains the most challenging issue for the final cure of the disease. PMID:26687281

  17. Treatment of severe acute pancreatitis and its complications.

    PubMed

    Zerem, Enver

    2014-10-14

    Severe acute pancreatitis (SAP), which is the most serious type of this disorder, is associated with high morbidity and mortality. SAP runs a biphasic course. During the first 1-2 wk, a pro-inflammatory response results in systemic inflammatory response syndrome (SIRS). If the SIRS is severe, it can lead to early multisystem organ failure (MOF). After the first 1-2 wk, a transition from a pro-inflammatory response to an anti-inflammatory response occurs; during this transition, the patient is at risk for intestinal flora translocation and the development of secondary infection of the necrotic tissue, which can result in sepsis and late MOF. Many recommendations have been made regarding SAP management and its complications. However, despite the reduction in overall mortality in the last decade, SAP is still associated with high mortality. In the majority of cases, sterile necrosis should be managed conservatively, whereas in infected necrotizing pancreatitis, the infected non-vital solid tissue should be removed to control the sepsis. Intervention should be delayed for as long as possible to allow better demarcation and liquefaction of the necrosis. Currently, the step-up approach (delay, drain, and debride) may be considered as the reference standard intervention for this disorder. PMID:25320523

  18. Treatment of Acute Puerperal Mastitis and Breast Abscess

    PubMed Central

    Cantlie, Helene Bertrand

    1988-01-01

    Mastitis is a benign infection of the breast if it is treated early. If two days elapse before treatment is started, it can lead to serious complications such as chronic or recurrent mastitis or breast abscess. Treatment consists in frequent nursing and massaging or stripping the breast to keep it empty of milk or pus, and appropriate antibiotics. Incision and drainage of a breast abscess can be done in the office under local anesthesia, and the drainage continued at home by the mother. PMID:21253250

  19. 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

  20. 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

    2016-04-01

    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. PMID:26826332

  1. The Rapid Effectiveness of Minocycline against Scrub Typhus Meningoencephalitis.

    PubMed

    Naoi, Tameto; Shimazaki, Haruo; Sawada, Mikio

    2016-01-01

    Scrub typhus is associated with various clinical symptoms. However, the pathogenesis of scrub typhus infection remains to be elucidated. A 73-year-old man was admitted to our hospital with consciousness disturbance and suspected meningoencephalitis. The patient's laboratory data showed deterioration and were indicative of hemophagocytic lymphohistiocytosis (HLH). A whole body examination to detect the trigger disease revealed an eschar, which is a characteristic of scrub typhus, on his back. His symptoms showed dramatic improvement after the administration of minocycline (MINO). This case report highlights that the clinical course of a case of scrub typhus meningoencephalitis that was cured with MINO. PMID:27041169

  2. Acute bilateral glaucoma and panuveitis as a side effect of topiramate for weight loss treatment.

    PubMed

    Pikkel, Yoav Yechezkel

    2014-01-01

    A 54-year-old male patient presented to our clinic with acute angle-closure glaucoma and panuveitis in both eyes after being treated with topiramate for binge eating and obesity. This case report emphasises the hazardous side effects of treatment with topiramate with unusual indication and the precaution a caretaker must take when treating a patient. PMID:24744070

  3. Effective treatment of migraine. Terminating acute attacks, reducing their frequency.

    PubMed

    Pringsheim, Tamara; Edmeads, John

    2004-04-01

    Migraine is the headache most commonly encountered in primary care practice. In one US population survey, 17.6% of women and 6% of men reported migraine. Specific, effective treatment options for migraine are increasingly available, helping to reinforce how important it is that this common and sometimes disabling condition be recognized by primary care physicians. PMID:15095534

  4. [Treatment of acute pelvic inflammatory diseases with a new antibiotic compound preparation (author's transl)].

    PubMed

    Burmucic, R

    1980-11-30

    48 patients with acute pelvic inflammatory diseases (35 cases of acute adnexitis and 13 cases of inflammatory adnexal tumours) were treated with an antibiotic combination of Ampicillin/Oxacillin and Sisomicin. As initial parenteral therapy Ampicillin/Oxacillin 3.0 g was given intravenously twice daily and additionally Sisomicin 75 or 100 mg according to the body-weight was administered intramuscular twice daily. If required a further oral treatment with 500 mg Ampicillin/Dicloxacillin capsules four times a day was carried out. The average duration of parenteral treatment was 6.3 days; together with the oral treatment the duration of antibiotic treatment was 18.5 days. In 43 patients (89.6%) the disease could be cured completely or a distinct improvement could be achieved. Only in 5 cases (10.4%) the results were unsatisfactory. As side-effects allergic reactions were observed in three cases and gastro-enteritis in one case. PMID:7467388

  5. Ibuprofen in the treatment of acute ankle joint injuries. A double-blind study.

    PubMed

    Fredberg, U; Hansen, P A; Skinhøj, A

    1989-01-01

    Sixty-eight patients who presented to the casualty ward with acute ankle joint injuries were studied to examine the effect of ibuprofen on pain and ankle swelling. Thirty-two patients were treated with placebo tablets and 36 with 600 mg ibuprofen tablets taken four times a day for 4 to 6 days. All of the patients were immobilized and requested to keep the foot elevated. The results showed that ibuprofen had no effect on the ankle swelling. The need for additional analgesics was not influenced by treatment with ibuprofen, which means that ibuprofen has no effect on pain. The time elapsed from occurrence of the injury to arrival at the casualty ward was negatively correlated to the reduction of ankle joint swelling during the treatment period. Treatment with ice-sprays, icebags, or cold water during the acute stage of injury did not influence the reduction of swelling during the treatment period. PMID:2675651

  6. Guidelines for the diagnosis and treatment of acute and subacute rhinosinusitis in children.

    PubMed

    Esposito, S; Principi, N

    2008-04-01

    The importance of rhinosinusitis finally reached pediatricians' attention a few years ago, and it has now been demonstrated that it is medically important and has a considerable socioeconomic impact in childhood. These guidelines, which have been prepared with and approved by many Italian Scientific Societies, are based on the most recent findings in the fields of clinical symptoms, imaging and microbiology tests for the diagnosis of acute rhinosinusitis, and efficacy evidence concerning antibiotic treatment and non-antibiotic adjuvant treatment. A Pubmed search using the key words "sinusitis", "rhinosinusitis", "child" and "antibiotic treatment", and the limits "human studies" and "English language", led to the selection of more than 2,700 articles published between 1966 and 2007. These guidelines are based on the 125 that were considered truly relevant and reflect the most widely shared positions concerning the diagnosis and treatment of acute, subacute and recurrent rhinosinusitis in children. PMID:18467238

  7. Stem cell technology for the treatment of acute and chronic renal failure

    PubMed Central

    Pino, Christopher J.; Humes, H. David

    2010-01-01

    Acute and chronic renal failure are disorders with high rates of morbidity and mortality. Current treatment is based upon conventional dialysis to provide volume regulation and small solute clearance. There is growing recognition that renal failure is a complex disease state requiring a multifactorial therapy to address the short-comings of the conventional monofactorial approach. Kidney transplantation remains the most effective treatment, however, organ availability lags far behind demand. Many key kidney functions including gluconeogenesis, ammoniagenesis, metabolism of glutathione, catabolism of important peptide hormones, growth factors, and cytokines critical to multiorgan homeostasis and immunomodulation are provided by renal tubule cells. Therefore, cell-based therapies are promising multifactorial treatment approaches. In this review, current stem cell technologies including adult stem cells, embryonic stem cells and induced pluripotent stem cells will be discussed as cell sources for the treatment of acute and chronic renal failure. PMID:20801413

  8. Stigma as a barrier to treatment for child acute malnutrition in Marsabit County, Kenya.

    PubMed

    Bliss, Jessica Robin; Njenga, Martin; Stoltzfus, Rebecca Joyce; Pelletier, David Louis

    2016-01-01

    Acute malnutrition affects millions of children each year, yet global coverage of life-saving treatment through the community-based management of acute malnutrition (CMAM) is estimated to be below 15%. We investigated the potential role of stigma as a barrier to accessing CMAM. We surveyed caregivers bringing children to rural health facilities in Marsabit County, Kenya, divided into three strata based on the mid-upper arm circumference of the child: normal status (n = 327), moderate acute malnutrition (MAM, n = 241) and severe acute malnutrition (SAM, n = 143). We used multilevel mixed effects logistic regression to estimate the odds of reporting shame as a barrier to accessing health care. We found that the most common barriers to accessing child health care were those known to be universally problematic: women's time and labour constraints. These constituted the top five most frequently reported barriers regardless of child acute malnutrition status. In contrast, the odds of reporting shame as a barrier were 3.64 (confidence interval: 1.66-8.03, P < 0.05) times higher in caregivers of MAM and SAM children relative to those of normal children. We conclude that stigma is an under-recognized barrier to accessing CMAM and may constrain programme coverage. In light of the large gap in coverage of CMAM, there is an urgent need to understand the sources of acute malnutrition-associated stigma and adopt effective means of de-stigmatization. PMID:25989353

  9. A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4

    PubMed Central

    Bastos, Leandro F. S.; Godin, Adriana M.; Zhang, Yingning; Jarussophon, Suwatchai; Ferreira, Bruno C. S.; Machado, Renes R.; Maier, Steven F.; Konishi, Yasuo; de Freitas, Rossimiriam P.; Fiebich, Bernd L.; Watkins, Linda R.; Coelho, Márcio M.; Moraes, Márcio F. D.

    2013-01-01

    Many studies have shown that minocycline, an antibacterial tetracycline, suppresses experimental pain. While minocycline’s positive effects on pain resolution suggest that clinical use of such drugs may prove beneficial, minocycline’s antibiotic actions and divalent cation (Ca2+; Mg2+) chelating effects detract from its potential utility. Thus, we tested the antiallodynic effect induced by a non-antibacterial, non-chelating minocycline derivative in a model of neuropathic pain and performed an initial investigation of its anti-inflammatory effects in vitro. Intraperitoneal minocycline (100 mg/kg) and 12S-hydroxy-1,12-pyrazolinominocycline (PMIN; 23.75, 47.50 or 95.00 mg/kg) reduce the mechanical allodynia induced by chronic constriction injury of mouse sciatic nerve. PMIN reduces the LPS-induced production of PGE2 by primary microglial cell cultures. Human embryonic kidney cells were transfected to express human toll-like receptors 2 and 4, and the signaling via both receptors stimulated with PAM3CSK4 or LPS (respectively) was affected either by minocycline or PMIN. Importantly, these treatments did not affect the cell viability, as assessed by MTT test. Altogether, these results reinforce the evidence that the anti-inflammatory and experimental pain suppressive effects induced by tetracyclines are neither necessarily linked to antibacterial nor to Ca2+ chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the management of neuropathic pain, as its lack of antibacterial and Ca2+ chelating activities might confer greater safety over conventional tetracyclines. PMID:23523650

  10. Attenuation of microglial activation with minocycline is not associated with changes in neurogenesis after focal traumatic brain injury in adult mice.

    PubMed

    Ng, Si Yun; Semple, Bridgette D; Morganti-Kossmann, M Cristina; Bye, Nicole

    2012-05-01

    Neurogenesis is stimulated following injury to the adult brain and could potentially contribute to tissue repair. However, evidence suggests that microglia activated in response to injury are detrimental to the survival of new neurons, thus limiting the neurogenic response. The aim of this study was to determine the effect of the anti-inflammatory drug minocycline on neurogenesis and functional recovery after a closed head injury model of focal traumatic brain injury (TBI). Beginning 30 min after trauma, minocycline was administered for up to 2 weeks and bromodeoxyuridine was given on days 1-4 to label proliferating cells. Neurological outcome and motor function were evaluated over 6 weeks using the Neurological Severity Score (NSS) and ledged beam task. Microglial activation was assessed in the pericontusional cortex and hippocampus at 1 week post-trauma, using immunohistochemistry to detect F4/80. Following immunolabeling of bromodeoxyuridine, double-cortin, and NeuN, cells undergoing distinct stages of neurogenesis, including proliferation, neuronal differentiation, neuroblast migration, and long-term survival, were quantified at 1 and 6 weeks in the hippocampal dentate gyrus, as well as in the subventricular zone of the lateral ventricles and the pericontusional cortex. Our results show that minocycline successfully reduced microglial activation and promoted early neurological recovery that was sustained over 6 weeks. We also show for the first time in the closed head injury model, that early stages of neurogenesis were stimulated in the hippocampus and subventricular zone; however, no increase in new mature neurons occurred. Contrary to our hypothesis, despite the attenuation of activated microglia, minocycline did not support neurogenesis in the hippocampus, lateral ventricles, or pericontusional cortex, with none of the neurogenic stages being affected by treatment. These data provide evidence that a general suppression of microglial activation is

  11. 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

  12. Minocycline activity tested against Acinetobacter baumannii complex, Stenotrophomonas maltophilia, and Burkholderia cepacia species complex isolates from a global surveillance program (2013).

    PubMed

    Flamm, Robert K; Castanheira, Mariana; Streit, Jennifer M; Jones, Ronald N

    2016-07-01

    Clinical isolates of Acinetobacter baumannii complex (1312), Stenotrophomonas maltophilia (464), and Burkholderia cepacia species complex (30) were selected from medical centers in the United States (USA), Europe and the Mediterranean (EU-M) region, Latin America, and Asia Pacific. Only one isolate per infected patient episode was included and local identifications were confirmed by the monitoring laboratory. Susceptibility testing was performed at the monitoring laboratory using the reference broth microdilution method as described by Clinical and Laboratory Standards Institute (CLSI). A. baumannii complex were classified as MDR (multi-drug resistant [MDR]; nonsusceptible to ≥1 agent in ≥3 antimicrobial classes) and extensively drug-resistant (XDR; nonsusceptible to ≥1 agent in all but ≤2 antimicrobial classes). A total of 81.6% of A. baumannii complex were MDR. Colistin was the most active agent against MDR A. baumannii complex. Minocycline was the most active "tetracycline" against these organisms based on susceptibility. Against B. cepacia, trimethoprim-sulfamethoxazole (MIC90, 2 μg/mL; 100.0% susceptible) was the most active agent tested. Overall, minocycline was the most active tetracycline tested against A. baumannii complex and S. maltophilia isolates collected from patients throughout EU-M, USA, Latin America, and the Asia-Pacific. Minocycline, particularly the intravenous formulation, has activity against several ESKAPE pathogens and merits consideration in seriously ill patients where treatment options may be limited due to the presence of MDR bacteria. PMID:27112832

  13. Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

    Cancer.gov

    This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes. |

  14. Acute Thrombotic Mesenteric Ischemia: Primary Endovascular Treatment in Eight Patients

    SciTech Connect

    Gagniere, Johan; Favrolt, Gregory; Alfidja, Agaiecha; Kastler, Adrian; Chabrot, Pascal; Cassagnes, Lucie; Buc, Emmanuel; Pezet, Denis; Boyer, Louis

    2011-10-15

    Introduction: The purpose of this study was to evaluate our experience with initial percutaneous transluminal angioplasty (PTA) {+-} stenting as valuable options in the acute setting. Methods: Between 2003 and 2008, eight patients with abdominal angio-MDCT-scan proven thrombotic AMI benefited from initial PTA {+-} stenting. We retrospectively assessed clinical and radiological findings and their management. Seven patients presented thrombosis of the superior mesenteric artery, and in one patient both mesenteric arteries were occluded. All patients underwent initial PTA and stenting, except one who had balloon PTA alone. One patient was treated by additional in situ thrombolysis. Results: Technical success was obtained in all patients. Three patients required subsequent surgery (37.5%), two of whom had severe radiological findings (pneumatosis intestinalis and/or portal venous gas). Two patients (25%) died: both had NIDD, an ASA score {>=}4, and severe radiologic findings. Satisfactory arterial patency was observed after a follow-up of 15 (range, 11-17) months in five patients who did not require subsequent surgery, four of whom had abdominal guarding but no severe CT scan findings. One patient had an ileocecal stenosis 60 days after the procedure. Conclusions: Initial PTA {+-} stenting is a valuable alternative to surgery for patients with thrombotic AMI even for those with clinical peritoneal irritation signs and/or severe radiologic findings. Early surgery is indicated if clinical condition does not improve after PTA. The decision of a subsequent surgery must be lead by early clinical status reevaluation. In case of underlying atherosclerotic lesion, stenting should be performed after initial balloon dilatation.

  15. Dalbavancin for the treatment of acute bacterial skin and skin structure infections.

    PubMed

    Esposito, Silvano; Noviello, Silvana; Leone, Sebastiano

    2015-12-01

    Dalbavancin is a novel parenteral lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults. Dalbavancin is highly active against common Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin has a prolonged half-life that allows for once weekly dosing. Phase III trials have demonstrated non-inferiority compared with vancomycin/linezolid in the treatment of ABSSSIs, including those sustained by MRSA. PMID:26700080

  16. Paliperidone palmitate injection for the acute and maintenance treatment of schizophrenia in adults

    PubMed Central

    Kim, Shiyun; Solari, Hugo; Weiden, Peter J; Bishop, Jeffrey R

    2012-01-01

    Purpose To review the use of paliperidone palmitate in treatment of patients with schizophrenia. Methods Published clinical trial data for the development and utilization of paliperidone palmitate for the treatment of schizophrenia were assessed in this review. Four short-term, randomized, double-blind, placebo-controlled trials investigated the efficacy of paliperidone palmitate in acute exacerbation of schizophrenia. Paliperidone palmitate was also studied as a maintenance treatment to prevent or delay relapse in stable schizophrenia. In addition, paliperidone palmitate was compared to risperidone long-acting injection for noninferiority in three studies. Results Paliperidone palmitate has been shown to be effective in reducing symptoms as measured by the Positive and Negative Syndrome Scale total scores in the four acute treatment studies. In the maintenance treatment studies, paliperidone palmitate was found to be more effective than placebo in preventing or delaying the time to first relapse in stable schizophrenia patients. In addition, paliperidone palmitate was shown to be noninferior to risperidone long-acting injection in two studies. It was shown to be reasonably well tolerated in all clinical trials. Acute treatment phase should be initiated with a dose of 234 mg on day one and 156 mg on day eight, followed by a recommended monthly maintenance dose of 39–234 mg based on efficacy and tolerability results from the clinical studies. Conclusion Providing an optimal long-term treatment can be challenging. Paliperidone palmitate can be used as an acute treatment even in outpatient setting, and it has shown to be well tolerated by patients. Also, it does not require overlapping oral antipsychotic supplementation while being initiated, and is dosed once per month. PMID:22879739

  17. [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. PMID:27106030

  18. Advancements in the treatment of pediatric acute leukemia and brain tumor - continuous efforts for 100% cure.

    PubMed

    Ju, Hee Young; Hong, Che Ry; Shin, Hee Young

    2014-10-01

    Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered. PMID:25379043

  19. [Acute hemorrhagic necrosis of the breast following treatment with Cumarin].

    PubMed

    Lüchtrath, H; Walkowsky, A

    1983-08-01

    A case of hemorrhagic necrosis of the breast is reported in a thirty-four year old woman who received Cumarin treatment for deep leg vein thrombosis and pulmonary embolism. It was necessary to remove the breast. The microscopic examination showed complete blockage of the vessels by fibrin thrombi in almost all veins. The cause of this venous thrombosis was explained as a Shwartzman-Sanarelli-Phenomenon. PMID:6555120

  20. Evolving strategies in the treatment of acute myocardial infarction-induced cardiogenic shock

    PubMed Central

    Tchantchaleishvili, Vakhtang; Schubmehl, Heidi; Swartz, Michael F.; Hallinan, William

    2014-01-01

    Despite advances in medical technology and re-vascularization interventions, the mortality rate for cardiogenic shock (CS) following acute myocardial infarction has remained at 50%. The majority of these mortalities are from left ventricular failure resulting in multi-system organ dysfunction. The field of mechanical circulatory support (MCS) has evolved within the past decade, with improved outcomes from extracorporeal membrane oxygenation as well as continuous-flow left ventricular assist devices (CF LVADs). In this paper, we discuss our institutional treatment strategies, the rationale for the protocol development, and our improved outcomes when using MCS in patients with refractory CS following acute myocardial infarction. PMID:25512903

  1. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    PubMed Central

    2012-01-01

    Objective Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments. PMID:23351279

  2. 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. PMID:21996647

  3. Treatment of mild to moderate pain of acute soft tissue injury: diflunisal vs acetaminophen with codeine.

    PubMed

    Muncie, H L; King, D E; DeForge, B

    1986-08-01

    Acute soft tissue injuries create pain and limitation of function. Treatment requires analgesia and time for full recovery. Acetaminophen with codeine (650 mg plus 60 mg, respectively, every 4 to 6 hours) is used frequently as the analgesic of choice. Diflunisal (1,000 mg initially then 500 mg twice a day) vs acetaminophen with codeine was prospectively studied in the treatment of acute mild to moderate pain from soft tissue injuries. Thirty-five patients with acute strains, sprains, or low back pain were randomized to treatment (17 acetaminophen with codeine vs 18 diflunisal). Both groups were similar in the amount of pain and type of injury at initiation of therapy. Patient pain rating went from 3.3 +/- 0.6 to 1.6 +/- 1.5 for acetaminophen with codeine and from 3.3 +/- 0.6 to 1.3 +/- 1.1 for diflunisal. However, 65 percent of acetaminophen with codeine patients experienced side effects, with 35 percent of these patients stopping the medication because of intolerable side effects. In the diflunisal group, 28 percent of the patients experienced side effects and 5 percent had to stop the medication early. Diflunisal was found to be an effective analgesic in mild to moderate pain of acute soft tissue injuries, and caused fewer and more tolerable side effects than did acetaminophen with codeine. PMID:2942630

  4. Acupuncture Treatment for Acute Ankle Injury in the Emergency Department: A Preliminary Case Report.

    PubMed

    Tantivesruangdet, Nopmanee

    2016-02-01

    Acupuncture is an ancient medical treatment that is increasingly attracting the interest of the public. It is a complementary therapy that is widely used for management of pain, especially chronic discomfort caused by migraine, low-back pain and osteoarthritis of the knee(¹⁻³). The evidence base for the effectiveness of acupuncture and its clinical applications is controversial, and although its efficacy and safety in the management of acute pain have been demonstrated, the quality of this modality is still questionable. The present study reports a case of acute ankle injury, which was treated with acupuncture. A 33-year-old man presented with acute twisted ankle injury. He had pain with swelling around the ankle, and he was experiencing difficulty in walking. His clinical diagnosis was acute ankle sprain with severe pain. Several drug treatments are used for pain control, but in this case, we used acupuncture. After treatment, his pain diminished significantly with a decrease in VAS pain level from 8 to 4 in 20 minutes. At follow-up after one month, we found no skin infection in this case. PMID:27266242

  5. Percutaneous cystic duct stent placement in the treatment of acute cholecystitis.

    PubMed

    Comin, Jules M; Cade, Richard J; Little, Andrew F

    2010-10-01

    Percutaneous cholecystostomy is well established as a temporising treatment option in selected patients presenting with acute cholecystitis. However, some patients who undergo cholecystostomy will have persistent discharge, which precludes catheter removal, or may not be medically suitable for future cholecystectomy. In these circumstances, percutaneous cystic duct stenting isa novel treatment option. It may delay or avoid the need for cholecystectomy, and thereby provide definitive treatment in a subset of patients who have acute cholecystitis and a high anaesthetic risk or limited life expectancy. Current application has been limited largely to patients with pre-existing malignant common bile duct strictures, but there is potential for the application to be broadened to include other subsets of patients. In this paper, we describe the technique used for percutaneous cystic duct stenting in a patient and report on its effectiveness. We also explore the technical considerations and consider the application of the procedure on other groups of patients. PMID:20976992

  6. [Open thrombectomy in treatment of acute thromboses of lower-limb deep veins].

    PubMed

    Shaĭdakov, E V; Porembskaia, O Ia; Tsarev, O I; Khmel'niker, S M

    2014-01-01

    Thrombosis of lower-limb deep veins is one of the most common vascular diseases in the world. For a long time the generally accepted treatment policy was conservative therapy with anticoagulants. The article is a review of the literature containing the results of studies carried out over the past two decades and confirming efficacy of surgical treatment for acute venous thrombosis. Presented are the data showing that thrombectomy performed within the first 10-14 days from the onset of the disease, improving quality of life of patients and preventing invalidization thereof. The gained world experience makes it possible to work out the most effective approaches to treatment of acute venous thromboses. PMID:25646547

  7. Effects of Repetitive Hyperbaric Oxygen Treatment in Patients with Acute Cerebral Infarction: A Pilot Study

    PubMed Central

    Chen, Cheng-Hsin; Chen, Shao-Yuan; Wang, Vinchi; Chen, Chao-Ching; Wang, Kaw-Chen; Chen, Chih-Hao; Liu, Yi-Chien; Lu, Kuo-Cheng; Yip, Ping-Keung; Ma, Wen-Ya; Liu, Chuan-Chieh

    2012-01-01

    The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This prospective study assessed the efficacy and safety of HBOT as adjuvant treatment on 46 acute ischemic stroke in patients who did not receive thrombolytic therapy. The HBOT group (n = 16) received conventional medical treatment with 10 sessions of adjunctive HBOT within 3–5 days after stroke onset, while the control group (n = 30) received the same treatment but without HBOT. Early (around two weeks after onset) and late (one month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. The baseline clinical characteristics were similar in both groups. Both early and late outcomes of the HBOT group showed significant difference (P ≤ 0.001). In the control group, there was only significant difference in early outcome (P = 0.004). For early efficacy, there was no difference when comparing changes of NIHSS scores between the two groups (P = 0.140) but there was statistically significant difference when comparing changes of NIHSS scores at one month (P ≤ 0.001). The HBOT used in this study may be effective for patients with acute ischemic stroke and is a safe and harmless adjunctive treatment. PMID:22919348

  8. Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment?

    PubMed

    Safioleas, Konstantinos; Giamarellos-Bourboulis, Evangelos J; Carrer, Dionyssia-Pinelopi; Pistiki, Aikaterini; Sabracos, Lambros; Deliveliotis, Charalambos; Chrisofos, Michael

    2016-05-01

    Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells. PMID:26844659

  9. Diagnosis and Treatment of Acute or Persistent Diarrhea

    PubMed Central

    Pawlowski, Sean W; Warren, Cirle Alcantara; Guerrant, Richard

    2009-01-01

    Studies of microbial pathogens and the toxins they produce are important for determining the mechanisms by which they cause disease and spread throughout a population. Some bacteria produce secretory enterotoxins (such as choleratoxin or the heat-labile or stable enterotoxins produced by E. coli) that invade cells directly. Others produce cytotoxins (such as those produced by Shigella, enteroinvasive E. coli, or C. difficile) that damage cells or trigger host responses that cause small or large bowel diseases (such as enteroaggregative or enteropathogenic E. coli or Salmonella). Viruses (such as noroviruses and rotaviruses) and protozoa (such as Cryptosporidium, Giardia or Entameba histolytica) disrupt cell functions and cause short- or long-term disease. Much epidemiological data about these pathogens have been collected from community- and hospital-acquired settings, as well from patients with traveler’s or persistent diarrhea. These studies have led to practical approaches for prevention, diagnosis and treatment. PMID:19457416

  10. Pharmacoeconomic benefits of almotriptan in the acute treatment of migraine.

    PubMed

    Freitag, Frederick G

    2008-04-01

    Almotriptan is one of seven oral triptans available in the USA and much of the rest of the world. Reviews of its efficacy and tolerability demonstrate it to be among the most effective and well tolerated of this class. Studies of almotriptan in a variety of early intervention paradigms demonstrate significant improvements in efficacy and further improved tolerability compared with standard treatment of headaches of at least moderate severity. The nature of migraine pain and symptoms is such as to produce impairment of the individual in their usual activities, including work, and leads to a significant cost of migraine to the workplace. Utilizing both specific studies examining this and drawing conclusions upon the results of additional trials suggests that, despite the direct costs of this agent, the economic advantages and personal advantages to the patients more than compensate. PMID:20528399

  11. Almotriptan: meeting today's needs in acute migraine treatment.

    PubMed

    Láinez, Miguel J A

    2007-12-01

    Migraine is a common disorder associated with considerable individual and economic burden. Triptans are recommended for the treatment of migraine of any severity in patients who have failed to gain adequate relief with nonspecific medication; early transition to triptans avoids prolonged morbidity in patients failing to respond to nonspecific medications. There is evidence that early intervention therapy with oral formulations in migraine, soon after the onset of an attack and when pain is still mild, improves efficacy. Seven different triptans are currently marketed, with differing pharmacologic, efficacy and tolerability profiles. Almotriptan has many positive features, which include rigorously demonstrated efficacy in sumatriptan nonresponders, as early therapy and in menstrual migraine. In addition, almotriptan has a favorable pharmacologic profile with a lack of clinically relevant pharmacokinetic interventions with other drugs, adverse reactions rate similar to placebo, superior cost-effectiveness and excellent performance on composite clinical outcome measures that incorporate features of greatest importance to patients. Although effective in both triptan-naive and -experienced patients, and as both early and standard therapy, almotriptan shows greater efficacy in triptan-naive patients and as early treatment, and is consistently one of the preferred triptans in multiattribute decision-making analyses incorporating attributes of significance for patients and physicians. Therefore, almotriptan has many features that make it an ideal choice for a triptan-naive patient moving from nonspecific medication, a patient switching from another triptan owing to inefficacy or tolerability issues and patients being advised to take a triptan early in the course of a migraine attack. PMID:18052762

  12. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System

    PubMed Central

    Lewis, Kate Marie; Turner, Renée Jade

    2013-01-01

    Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis. PMID:23819099

  13. 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

  14. Developing drug strategies for the neuroprotective treatment of acute ischemic stroke.

    PubMed

    Tuttolomondo, Antonino; Pecoraro, Rosaria; Arnao, Valentina; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2015-01-01

    Developing new treatment strategies for acute ischemic stroke in the last twenty years has offered some important successes, but also several failures. Most trials of neuroprotective therapies have been uniformly negative to date. Recent research has reported how excitatory amino acids act as the major excitatory neurotransmitters in the cerebral cortex and hippocampus. Furthermore, other therapeutic targets such as free radical scavenger strategies and the anti-inflammatory neuroprotective strategy have been evaluated with conflicting data in animal models and human subjects with acute ischemic stroke. Whereas promising combinations of neuroprotection and neurorecovery, such as citicoline, albumin and cerebrolysin have been tested with findings worthy of further evaluation in larger randomized clinical trials. Understanding the complexities of the ischemic cascade is essential to developing pharmacological targets for acute ischemic stroke in neuroprotective or flow restoration therapeutic strategies. PMID:26469760

  15. Novel immunotherapeutic approaches for the treatment of acute leukemia (myeloid and lymphoblastic).

    PubMed

    Ishii, Kazusa; Barrett, Austin J

    2016-02-01

    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

  16. Elemental diet as primary treatment of acute Crohn's disease: a controlled trial.

    PubMed

    O'Moráin, C; Segal, A W; Levi, A J

    1984-06-23

    Acute exacerbations of Crohn's disease are usually treated with prednisolone or potentially more toxic immunosuppressive drugs or by surgery. In pilot studies replacing the normal diet by a protein free elemental diet also induced remission. A controlled trial was therefore conducted in which 21 patients acutely ill with exacerbations of Crohn's disease were randomised to receive either prednisolone 0.75 mg/kg/day or an elemental diet (Vivonex) for four weeks. Assessment at four and 12 weeks showed that the patients treated with the elemental diet had improved as much as and by some criteria more than the steroid treated group. Elemental diet is a safe and effective treatment for acute Crohn's disease. PMID:6428577

  17. Uptake of Minocycline and Tetracycline by Tetracycline-Susceptible and -Resistant Bacteria

    PubMed Central

    Kuck, N. A.; Forbes, M.

    1973-01-01

    Minocycline (7-dimethylamino-6-demethyl-6-deoxytetracycline) is a new semisynthetic tetracycline with potent activity against tetracycline-susceptible bacterial pathogens and unique activity against tetracycline-resistant staphylococci. Studies to determine the basis for this unique activity showed that, whereas tetracycline-resistant staphylococci took up less 3H-tetracycline than the susceptible cells, both the tetracycline-resistant and -susceptible cells accumulated equivalent amounts of 14C-minocycline. In contrast, tetracycline-resistant Escherichia coli cells were relatively resistant to minocycline and accumulated less of both drugs than did the susceptible organisms. It is proposed that minocycline is effective against tetracycline-resistant staphylococci because of its ability to penetrate the cells sufficiently to reach inhibiting concentrations at sensitive reaction sites. PMID:4597735

  18. Impact of Oxandrolone Treatment on Acute Outcomes After Severe Burn Injury

    PubMed Central

    Pham, Tam N.; Klein, Matthew B.; Gibran, Nicole S.; Arnoldo, Brett D.; Gamelli, Richard L.; Silver, Geoffrey M.; Jeschke, Marc G.; Finnerty, Celeste C.; Tompkins, Ronald G.; Herndon, David N.

    2013-01-01

    Pharmacologic modulation of hypermetabolism clearly benefits children with major burns, however, its role in adult burns remains to be defined. Oxandrolone appears to be a promising anabolic agent although few outcome data are as yet available. We examined whether early oxandrolone treatment in severely burned adults was associated with improved outcomes during acute hospitalization. We evaluated for potential associations between oxandrolone treatment and outcomes in a large cohort of severely burned adults in the context of a multicenter observational study. Patients were dichotomized with respect to oxandrolone treatment, defined as administration within 7 days after admission, with duration of at least 7 days. Acute hospitalization outcomes were compared with univariate and multivariate analyses. One hundred seventeen patients were included in this analysis. Mean patient age was 42.6 years (range, 18–86); 77% were male, with an average TBSA of 44.1%. Baseline and injury characteristics were similar among treatment and nontreatment cohorts. Oxandrolone treatment (N =59) did not impact length of stay but was associated with a lower mortality rate (P = .01) by univariate analysis. Oxandrolone treatment was independently associated with higher survival by adjusted analyses (P = .02). Examination of early oxandrolone treatment in this cohort of severely burned adults suggests that this therapy is safe and may be associated with improved survival. Further studies are necessary to define the exact mechanisms by which oxandrolone is beneficial during inpatient treatment. PMID:18849836

  19. Reversible Posterior Leukoencephalopathy Syndrome Associated with Treatment for Acute Exacerbation of Ulcerative Colitis.

    PubMed

    Kikuchi, Shinsuke; Orii, Fumika; Maemoto, Atsuo; Ashida, Toshifumi

    2016-01-01

    Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical syndrome of varying etiologies with similar neuroimaging findings. This is a case report of a 25-year-old woman who developed typical, neurological symptoms and magnetic resonance imaging abnormalities after treatment for the acute exacerbation of ulcerative colitis (UC), which included blood transfusion, the systemic administration of prednisolone, and the administration of metronidazole. It has been reported that these treatments may contribute to the development of RPLS. RPLS should therefore be considered in the differential diagnosis of UC patients who exhibit impaired consciousness, seizures or visual deficits during treatment. We report a rare case of RPLS in a patient with UC. PMID:26935366

  20. Catheter-directed thrombolysis in the treatment of acute deep venous thrombosis: a meta-analysis.

    PubMed

    Zheng, J J; Zhang, Z H; Shan, Z; Wang, W J; Li, X X; Wang, S M; Li, Y-X; Cheng, G-S

    2014-01-01

    We performed a meta-analysis for systematic evaluation of the status quo of catheter thrombolysis for the treatment of acute lower limb deep vein thrombosis in China. We searched the China Biomedical bibliographic database (CBM), China National Knowledge Infrastructure (CNKI), Weipu full-text electronic journals, Wanfang full-text database, and Medline (1990 through June 2011) for clinical randomized controlled trials of catheter-directed thrombolysis and superficial venous thrombolysis to compare their efficacies for the treatment of acute deep vein thrombosis. The results were analyzed by using the Cochrane-recommended RevMan 4.2 software package, and the odds ratio (OR) was used as the combined measure of efficacy. The search retrieved 8 randomized controlled trials, and meta-analysis using the total rate of effective treatment as the clinical observation index found that the combined OR for the catheter thrombolysis group versus the superficial venous thrombolysis group was significant (P < 0.01; OR = 11.78; 95% confidence interval = 6.99-19.87). In conclusion, the meta-analysis indicated that catheter thrombolysis was more effective than superficial venous thrombolysis for the treatment of acute deep vein thrombosis in the lower limb in Chinese individuals. However, the included trials were only of medium quality, so more rational and scientific clinical trials are needed to validate this conclusion. PMID:25078578

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

    SciTech Connect

    Carrafiello, Gianpaolo Fontana, Federico Mangini, Monica Ierardi, Anna Maria Lagana, Domenico; Piacentino, Filippo Vizzari, Francesco Alberto Spano, Emanuela Fugazzola, Carlo

    2012-06-15

    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 fracture 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.

  2. Changing Trends in Treatment of Acute Mania: Experience of a Tertiary Centre Over a Decade.

    PubMed

    Arıkan, Mehmet Kemal; Poyraz, Cana Aksoy; Baş, Alper; Sağlam, N Gamze Usta; Batun, Gizem Cetiner; Gültekin, Gözde; Poyraz, Burç Çağrı

    2016-06-01

    We investigated trends over a decade in the prescription of lithium, antiepileptics, and antipsychotic agents at discharge for patients hospitalised for acute mania. We conducted a retrospective review of medical records for 165 inpatients with acute mania who had been hospitalised in Cerrahpaşa Faculty of Medicine, Department of Psychiatry during 2001-2002 and 2011-2012. Among 165 patients, prescription of olanzapine at discharge increased from 3 to 46 % (p < 0.001), while prescription of haloperidol decreased from 55 to 21 % (p < 0.001). Use of other atypical antipsychotics did not change significantly (risperidone decreased from 14 to 11 %, p = 0.5; quetiapine increased from 10 to 16 %, p = 0.2). Use of valproate, carbamazepine, and lithium did not change significantly. Use of electroconvulsive therapy in acute mania decreased by half from 27 to 13 % (p = 0.02). Typical antipsychotics alone or in combination with antiepileptics were the most common treatment regimen at discharge at 2001-2002; while 10 years later, they had been largely replaced by lithium or antiepileptics combined with second generation antipsychotics. Antipsychotic agents remained to be an important component of acute treatment of mania in our practice. PMID:26220636

  3. Relaxin for the Treatment of Acute Decompensated Heart Failure: Pharmacology, Mechanisms of Action, and Clinical Evidence.

    PubMed

    Ng, Tien M H; Goland, Sorel; Elkayam, Uri

    2016-01-01

    Acute heart failure remains a major cause of morbidity, and its treatment requires an increasing investment of the health care system. Whereas success in treating chronic heart failure has been achieved over the last decades, several pharmacological approaches for acute heart failure have been introduced but have failed to demonstrate any clinical benefit. Serelaxin is a recombinant human relaxin-2 vasoactive peptide that causes systemic and renal vasodilation. Data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via neurohormonal, anti-inflammatory, antiremodeling, antifibrotic, anti-ischemic, and proangiogenic effects. Recently, a number of clinical trials have demonstrated that serelaxin infusion over 48 hours improved dyspnea with more rapid relief of congestion during the first days after admission for heart failure. In addition, administration of serelaxin diminished cardiac, renal, and hepatic damage, which were associated with improved long-term mortality. Available data support substantial clinical benefits and significant promise for serelaxin as a treatment option for patients with acute heart failure. This review focuses on the pharmacology and mechanisms of action of serelaxin and provides a detailed discussion of the clinical evidence for this novel therapy in acute heart failure. PMID:26331289

  4. [Complementary treatment of acute heart failure in patients with diabetes, chronic obstructive pulmonary disease or anemia].

    PubMed

    Carrasco Sánchez, Francisco Javier; Recio Iglesias, Jesús; Grau Amorós, Jordi

    2014-03-01

    Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF. PMID:24930086

  5. Anticoagulant treatment for acute pulmonary embolism: a pathophysiology-based clinical approach.

    PubMed

    Agnelli, Giancarlo; Becattini, Cecilia

    2015-04-01

    The management of patients with acute pulmonary embolism is made challenging by its wide spectrum of clinical presentation and outcome, which is mainly related to patient haemodynamic status and right ventricular overload. Mechanical embolic obstruction and neurohumorally mediated pulmonary vasoconstriction are responsible for right ventricular overload. The pathophysiology of acute pulmonary embolism is the basis for risk stratification of patients as being at high, intermediate and low risk of adverse outcomes. This risk stratification has been advocated to tailor clinical management according to the severity of pulmonary embolism. Anticoagulation is the mainstay of the treatment of acute pulmonary embolism. New direct oral anticoagulants, which are easier to use than conventional anticoagulants, have been compared with conventional anticoagulation in five randomised clinical trials including >11 000 patients with pulmonary embolism. Patients at high risk of pulmonary embolism (those with haemodynamic compromise) were excluded from these studies. Direct oral anticoagulants have been shown to be as effective and at least as safe as conventional anticoagulation in patients with pulmonary embolism without haemodynamic compromise, who are the majority of patients with this disease. Whether these agents are appropriate for the acute-phase treatment of patients at intermediate-high risk pulmonary embolism (those with both right ventricle dysfunction and injury) regardless of any risk stratification remains undefined. PMID:25700388

  6. Minocycline attenuates post-operative cognitive impairment in aged mice by inhibiting microglia activation.

    PubMed

    Wang, Hui-Lin; Liu, Hua; Xue, Zhang-Gang; Liao, Qing-Wu; Fang, Hao

    2016-09-01

    Although it is known that isoflurane exposure or surgery leads to post-operative cognitive dysfunction in aged rodents, there are few clinical interventions and treatments available to prevent this disorder. Minocycline (MINO) produces neuroprotection from several neurodegenerative diseases and various experimental animal models. Therefore, we set out to investigate the effects of MINO pre-treatment on isoflurane or surgery induced cognitive impairment in aged mice by assessing the hippocampal-dependent spatial memory performance using the Morris water maze task. Hippocampal tissues were isolated from mice and evaluated by Western blot analysis, immunofluorescence procedures and protein array system. Our results elucidate that MINO down-regulated the isoflurane-induced and surgery-induced enhancement in the protein levels of pro-inflammatory cytokine tumour necrosis factor alpha, interleukin (IL)-1β, interferon-γ and microglia marker Iba-1, and up-regulated protein levels of the anti-inflammatory cytokine IL-4 and IL-10. These findings suggest that pre-treatment with MINO attenuated isoflurane or surgery induced cognitive impairment by inhibiting the overactivation of microglia in aged mice. PMID:27061744

  7. 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. PMID:25833102

  8. Minocycline chelates Ca2+, binds to membranes, and depolarizes mitochondria by formation of Ca2+-dependent ion channels

    PubMed Central

    Antonenko, Yuri N.; Rokitskaya, Tatyana I.; Cooper, Arthur J. L.

    2010-01-01

    Minocycline (an anti-inflammatory drug approved by the FDA) has been reported to be effective in mouse models of amyotrophic lateral sclerosis and Huntington disease. It has been suggested that the beneficial effects of minocycline are related to its ability to influence mitochondrial functioning. We tested the hypothesis that minocycline directly inhibits the Ca2+-induced permeability transition in rat liver mitochondria. Our data show that minocycline does not directly inhibit the mitochondrial permeability transition. However, minocycline has multiple effects on mitochondrial functioning. First, this drug chelates Ca2+ ions. Secondly, minocycline, in a Ca2+-dependent manner, binds to mitochondrial membranes. Thirdly, minocycline decreases the proton-motive force by forming ion channels in the inner mitochondrial membrane. Channel formation was confirmed with two bilayer lipid membrane models. We show that minocycline, in the presence of Ca2+, induces selective permeability for small ions. We suggest that the beneficial action of minocycline is related to the Ca2+-dependent partial uncoupling of mitochondria, which indirectly prevents induction of the mitochondrial permeability transition. PMID:20180001

  9. Minocycline chelates Ca2+, binds to membranes, and depolarizes mitochondria by formation of Ca2+-dependent ion channels.

    PubMed

    Antonenko, Yuri N; Rokitskaya, Tatyana I; Cooper, Arthur J L; Krasnikov, Boris F

    2010-04-01

    Minocycline (an anti-inflammatory drug approved by the FDA) has been reported to be effective in mouse models of amyotrophic lateral sclerosis and Huntington disease. It has been suggested that the beneficial effects of minocycline are related to its ability to influence mitochondrial functioning. We tested the hypothesis that minocycline directly inhibits the Ca(2+)-induced permeability transition in rat liver mitochondria. Our data show that minocycline does not directly inhibit the mitochondrial permeability transition. However, minocycline has multiple effects on mitochondrial functioning. First, this drug chelates Ca(2+) ions. Secondly, minocycline, in a Ca(2+)-dependent manner, binds to mitochondrial membranes. Thirdly, minocycline decreases the proton-motive force by forming ion channels in the inner mitochondrial membrane. Channel formation was confirmed with two bilayer lipid membrane models. We show that minocycline, in the presence of Ca(2+), induces selective permeability for small ions. We suggest that the beneficial action of minocycline is related to the Ca(2+)-dependent partial uncoupling of mitochondria, which indirectly prevents induction of the mitochondrial permeability transition. PMID:20180001

  10. Enhancement of antinociception by coadminstration of minocycline and a non-steroidal anti-inflammatory drug indomethacin in naïve mice and murine models of LPS-induced thermal hyperalgesia and monoarthritis

    PubMed Central

    2010-01-01

    Background Minocycline and a non-steroidal anti-inflammatory drug (NSAID) indomethacin, have anti-inflammatory activities and are both used in the management of rheumatoid arthritis. However, there are no reports on whether coadministration of these drugs could potentiate each other's activities in alleviating pain and weight bearing deficits during arthritis. Methods LPS was injected to BALB/c mice intraperitoneally (i.p.) to induce thermal hyperalgesia. The hot plate test was used to study thermal nociception in naïve BALB/c and C57BL/6 mice and BALB/c mice with LPS-induced thermal hyperalgesia and to evaluate antinociceptive effects of drugs administered i.p. Monoarthritis was induced by injection of LPS intra-articularly into the right hind (RH) limb ankle joint of C57BL/6 mice. Weight bearing changes and the effect of i.p. drug administration were analyzed in freely moving mice using the video-based CatWalk gait analysis system. Results In naïve mice indomethacin (5 to 50 mg/kg) had no significant activity, minocycline (25 to 100 mg/kg) produced hyperalgesia to thermal nociception, however, coadministration of minocycline 50 mg/kg with indomethacin 5 or 10 mg/kg produced significant antinociceptive effects in the hot plate test. A selective inhibitor of COX-1, FR122047 (10 mg/kg) and a selective COX-2 inhibitor, CAY10404 (10 mg/kg) had no significant antinociceptive activities to thermal nociception in naïve mice, however, coadministration of minocycline, with CAY10404 but not FR122047 produced significant antinociceptive effects. In mice with LPS-induced hyperalgesia vehicle, indomethacin (10 mg/kg) or minocycline (50 mg/kg) did not produce significant changes, however, coadministration of minocycline plus indomethacin resulted in antinociceptive activity. LPS-induced RH limb monoarthritis resulted in weight bearing (RH/left hind (LH) limb paw pressure ratios) and RH/LH print area ratios deficits. Treatment with indomethacin (1 mg/kg) or minocycline (50 mg

  11. Conservative Treatment Is Sufficient for Acute Distal Radioulnar Joint Instability With Distal Radius Fracture.

    PubMed

    Lee, Sang Ki; Kim, Kap Jung; Cha, Yong Han; Choy, Won Sik

    2016-09-01

    Treatments for acute distal radioulnar joint (DRUJ) instability with distal radius fracture vary from conservative to operative treatment, although it seems to be no consensus regarding which treatment is optimal. This prospective randomized study was designed to compare the clinical outcomes for operative and conservative treatment of acute DRUJ instability with distal radius fracture, according to the presence or absence and type of ulnar styloid process fracture and the degree of its displacement. Between July 2008 and February 2013, we enrolled 157 patients who exhibited an unstable DRUJ during intraoperative manual stress testing (via the ballottement test) after fixation of the distal radius. Patients were classified according to the type of the ulnar styloid process fracture, using preoperative wrist radiography, and each group was divided into subgroups, according to their treatment method. We then compared the clinical outcomes between the conservative and operative treatments, using their range of motion; Disabilities of the Arm, Shoulder, and Hand score; modified Mayo wrist score; and grip strength. At 3 months after surgery, among patients without ulnar styloid process fracture, the flexion-extension range was 79 ± 15° after supination sugar-tong splinting (group A-1), 91 ± 14° after DRUJ transfixation (group A-2), and 89 ± 10° after arthroscopic triangular fibrocartilage complex repair (group A-3); the operative treatments provided greater joint motion ranges than conservative treatment. The groups with ulnar styloid process fractures at the tip (group B) or base (group C) also exhibited better clinical outcomes after the operative treatments, compared with after the conservative treatment. However, at the final follow-up, groups A-1, A-2, and A-3 exhibited similar flexion-extension ranges (122 ± 25°, 119° ± 18°, and 120° ± 16°, respectively) and modified Mayo wrist scores (87 ± 7, 89 ± 8, and 85 ± 9). Thus, the conservative and

  12. Chronic oral administration of minocycline to sheep with ovine CLN6 neuronal ceroid lipofuscinosis maintains pharmacological concentrations in the brain but does not suppress neuroinflammation or disease progression

    PubMed Central

    2013-01-01

    Background The neuronal ceroid lipofuscinoses (NCLs; or Batten disease) are fatal inherited human neurodegenerative diseases affecting an estimated 1:12,500 live births worldwide. They are caused by mutations in at least 11 different genes. Currently, there are no effective treatments. Progress into understanding pathogenesis and possible therapies depends on studying animal models. The most studied animals are the CLN6 South Hampshire sheep, in which the course of neuropathology closely follows that in affected children. Neurodegeneration, a hallmark of the disease, has been linked to neuroinflammation and is consequent to it. Activation of astrocytes and microglia begins prenatally, starting from specific foci associated with the later development of progressive cortical atrophy and the development of clinical symptoms, including the occipital cortex and blindness. Both neurodegeneration and neuroinflammation generalize and become more severe with increasing age and increasing clinical severity. The purpose of this study was to determine if chronic administration of an anti-inflammatory drug, minocycline, from an early age would halt or reverse the development of disease. Method Minocycline, a tetracycline family antibiotic with activity against neuroinflammation, was tested by chronic oral administration of 25 mg minocycline/kg/day to presymptomatic lambs affected with CLN6 NCL at 3 months of age to 14 months of age, when clinical symptoms are obvious, to determine if this would suppress neuroinflammation or disease progression. Results Minocycline was absorbed without significant rumen biotransformation to maintain pharmacological concentrations of 1 μM in plasma and 400 nM in cerebrospinal fluid, but these did not result in inhibition of microglial activation or astrocytosis and did not change the neuronal loss or clinical course of the disease. Conclusion Oral administration is an effective route for drug delivery to the central nervous system in large

  13. The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies.

    PubMed

    Marmura, Michael J; Silberstein, Stephen D; Schwedt, Todd J

    2015-01-01

    The study aims to provide an updated assessment of the evidence for individual pharmacological therapies for acute migraine treatment. Pharmacological therapy is frequently required for acutely treating migraine attacks. The American Academy of Neurology Guidelines published in 2000 summarized the available evidence relating to the efficacy of acute migraine medications. This review, conducted by the members of the Guidelines Section of the American Headache Society, is an updated assessment of evidence for the migraine acute medications. A standardized literature search was performed to identify articles related to acute migraine treatment that were published between 1998 and 2013. The American Academy of Neurology Guidelines Development procedures were followed. Two authors reviewed each abstract resulting from the search and determined whether the full manuscript qualified for review. Two reviewers studied each qualifying full manuscript for its level of evidence. Level A evidence requires at least 2 Class I studies, and Level B evidence requires 1 Class I or 2 Class II studies. The specific medications - triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan [oral, nasal spray, injectable, transcutaneous patch], zolmitriptan [oral and nasal spray]) and dihydroergotamine (nasal spray, inhaler) are effective (Level A). Ergotamine and other forms of dihydroergotamine are probably effective (Level B). Effective nonspecific medications include acetaminophen, nonsteroidal anti-inflammatory drugs (aspirin, diclofenac, ibuprofen, and naproxen), opioids (butorphanol nasal spray), sumatriptan/naproxen, and the combination of acetaminophen/aspirin/caffeine (Level A). Ketoprofen, intravenous and intramuscular ketorolac, flurbiprofen, intravenous magnesium (in migraine with aura), and the combination of isometheptene compounds, codeine/acetaminophen and tramadol/acetaminophen are probably effective (Level B). The antiemetics prochlorperazine

  14. Factors associated with marketable milk production recovery after treatment of naturally occurring acute coliform mastitis.

    PubMed

    Shinozuka, Yasunori; Kaneko, Sohei; Kurose, Tomoyasu; Watanabe, Aiko; Kuruhara, Kana; Kawai, Kazuhiro

    2016-06-01

    Milk production loss after recovery from acute coliform mastitis causes major economic losses for dairy industries. Declines in milk production and composition are caused by multiple factors, including cow factors, microorganisms and treatments, but the influence of each factor has not been determined. To investigate risk factors for milk loss after treatment for acute coliform mastitis, multiple logistic regression analyses were conducted in 53 clinical cases. Systemic administration of fluoroquinolone was significantly associated with recovery of marketable milk production. The time to slaughter was significantly shorter in cows with complete loss of quarter milk production than in cows that produced marketable milk. In this study, we identified factors associated with increased risk of milk production loss. PMID:26860356

  15. Mild axonal neuropathy of children during treatment for acute lymphoblastic leukaemia.

    PubMed

    Reinders-Messelink, H A; Van Weerden, T W; Fock, J M; Gidding, C E; Vingerhoets, H M; Schoemaker, M M; Göeken, L N; Bökkerink, J P; Kamps, W A

    2000-01-01

    Neurophysiological functioning was studied prospectively in children treated for acute lymphoblastic leukaemia with a low dose vincristine regime (8 x 1.5 mg/m2/dose), to obtain more insight into vincristine neuropathy. A WHO neurotoxicity score was estimated and vibration sense and electrophysiological measurements were taken at standardized times during vincristine treatment. The WHO neurotoxicity score showed decreased or disappearance of Achilles tendon reflexes, and mild sensory disturbances, but a grade 3-4 neurotoxicity was not demonstrated by any of the children. Vibration perception thresholds increased progressively during treatment and amplitudes of action potentials of peroneal and sensory ulnar and median nerves decreased, whereas nerve conduction velocities stayed unchanged. Both vibration perception thresholds and the electrophysiological findings hardly exceeded the limits of normality. We conclude that children treated for acute lymphoblastic leukaemia with a low dose vincristine regimen have mild axonal neuropathy which may be responsible for the motor problems in these children. PMID:11030069

  16. Factors associated with marketable milk production recovery after treatment of naturally occurring acute coliform mastitis

    PubMed Central

    SHINOZUKA, Yasunori; KANEKO, Sohei; KUROSE, Tomoyasu; WATANABE, Aiko; KURUHARA, Kana; KAWAI, Kazuhiro

    2016-01-01

    Milk production loss after recovery from acute coliform mastitis causes major economic losses for dairy industries. Declines in milk production and composition are caused by multiple factors, including cow factors, microorganisms and treatments, but the influence of each factor has not been determined. To investigate risk factors for milk loss after treatment for acute coliform mastitis, multiple logistic regression analyses were conducted in 53 clinical cases. Systemic administration of fluoroquinolone was significantly associated with recovery of marketable milk production. The time to slaughter was significantly shorter in cows with complete loss of quarter milk production than in cows that produced marketable milk. In this study, we identified factors associated with increased risk of milk production loss. PMID:26860356

  17. Refusal of treatment for acute leukemia in pregnancy: a case report

    PubMed Central

    2013-01-01

    Introduction Acute leukemia is rare in pregnancy. The importance of promptly diagnosing and treating this disease in pregnancy stems from its life-threatening potential, both to the mother and fetus. Case presentation We report a case of relapse of acute myeloid leukemia at 23 weeks of pregnancy in a 24-year-old Albanian woman. Our patient categorically refused chemotherapy treatment, and in her 35th week of gestation, severe hemorrhagic diathesis rapidly developed. The manifestation and course of this life-threatening complication posed therapeutic challenges for the attending medical team. Conclusion Based both on our experience and the results of other gynecological studies, there exists a strong indication that the earlier a patient’s chemotherapy treatment begins, the better the maternal outcome. We support chemotherapy for patients who are pregnant presenting with such illness. The present case report testifies that refusal of chemotherapy by such patients is a high-risk decision. PMID:23725005

  18. Oral carvedilol in escalating doses in the acute treatment of atrial fibrillation

    PubMed Central

    Chitrapu, Ravi Venkatachelam; Rao, Pentakota Ramana; Reddy, Gangireddy Venkateswara

    2014-01-01

    Objective: To study the efficacy of oral carvedilol in acute treatment of atrial fibrillation (AF) with fast ventricular rate. Materials and Methods: In an open-label, single-arm trial, oral carvedilol was administered to 35 patients of AF in escalating doses from 3.125 mg o.d. to 12.5 mg b.i.d. Results: A successful result was seen in 25 patients (71.4%) with 4 converting to sinus rhythm, rate control to less than 90 bpm in 16 and a 20% rate reduction in 5 patients. Two patients developed hypotension needing withdrawal of the drug. Conclusion: Escalating doses of oral carvedilol can be effectively and safely used in the acute treatment of AF with fast ventricular rate. PMID:25422563

  19. Treatment disparities in acute coronary syndromes, heart failure, and kidney disease.

    PubMed

    McCullough, Peter A; Maynard, Robert C

    2011-01-01

    It has been consistently observed that patients with renal dysfunction have more premature, severe, complicated, and fatal cardiovascular disease than age- and sex-matched individuals with normal renal function. There have been 4 major explanations for this finding: (1) positive confounding by third variables associated with chronic kidney disease (CKD), including diabetes mellitus and hypertension; (2) therapeutic nihilism or lesser use of beneficial therapies in CKD; (3) greater toxicities of therapies, such as bleeding from anticoagulants or contrast-induced kidney injury; (4) biological factors which result directly from CKD that work to promote and accelerate cardiovascular disease. In this paper, we focus on the issue of treatment disparities or therapeutic nihilism and its contribution to poor outcomes in the setting of acute coronary syndromes and acutely decompensated heart failure. This issue is important because if we can overcome barriers to the utilization of beneficial treatments, then clinical outcomes should improve over time. PMID:21625092

  20. Acute Osteochondral Fractures in the Lower Extremities - Approach to Identification and Treatment

    PubMed Central

    Pedersen, M.E; DaCambra, M.P; Jibri, Z; Dhillon, S; Jen, H; Jomha, N.M

    2015-01-01

    Chondral and osteochondral fractures of the lower extremities are important injuries because they can cause pain and dysfunction and often lead to osteoarthritis. These injuries can be misdiagnosed initially which may impact on the healing potential and result in poor long-term outcome. This comprehensive review focuses on current pitfalls in diagnosing acute osteochondral lesions, potential investigative techniques to minimize diagnostic errors as well as surgical treatment options. Acute osteochondral fractures are frequently missed and can be identified more accurately with specific imaging techniques. A number of different methods can be used to fix these fractures but attention to early diagnosis is required to limit progression to osteoarthritis. These fractures are common with joint injuries and early diagnosis and treatment should lead to improved long term outcomes. PMID:26587063

  1. Arthroscopic treatment of acute acromioclavicular joint dislocation with double flip button.

    PubMed

    Murena, L; Vulcano, Ettore; Ratti, C; Cecconello, L; Rolla, P R; Surace, M F

    2009-12-01

    The ideal treatment for acute acromioclavicular joint dislocation is still controversial, both in terms of indications and surgical technique. The clinical and radiographic outcomes of 16 patients affected by acute AC joint dislocation (type III-V) and arthroscopically treated with a coracoclavicular double flip button are presented. Despite the excellent clinical results both in terms of Constant score (mean 97 points) and patient satisfaction, at a mean follow-up of 31 months the radiographs showed partial loss of reduction due to distal migration of the flip button within the upper third of the clavicle in one-fourth of the cases. The technique presented here proved to be safe and minimally invasive while delivering good aesthetic results and allowing for the treatment of associated lesions. Furthermore, the technique could benefit from more advanced retention devices, which ought to reduce or avoid migration of the flip buttons. PMID:19554311

  2. Wilderness Medical Society practice guidelines for the treatment of acute pain in remote environments: 2014 update.

    PubMed

    Russell, Katie W; Scaife, Courtney L; Weber, David C; Windsor, Jeremy S; Wheeler, Albert R; Smith, William R; Wedmore, Ian; McIntosh, Scott E; Lieberman, James R

    2014-12-01

    The Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the management of pain in austere environments. Recommendations are graded on the basis of the quality of supporting evidence as defined by criteria put forth by the American College of Chest Physicians. This is an updated version of the original WMS Practice Guidelines for the Treatment of Acute Pain in Remote Environments published in Wilderness & Environmental Medicine 2014;25(1):41-49. PMID:25498266

  3. Treatment of acute cervical internal carotid artery dissection using the Solitaire FR revascularization device.

    PubMed

    To, Chiu Yuen; Badr, Yaser; Richards, Boyd

    2012-01-01

    During treatment of a right internal carotid artery terminus aneurysm, an acute iatrogenic flow limiting dissection was caused in the cervical internal carotid. The true lumen was catheterized using a Mirage 0.008 microwire over an Excelsior SL-10 microcatheter, which was exchanged for a Marksman microcatheter. A 6 mm×30 mm Solitaire FR revascularization device was then deployed across the dissection as a salvage technique. PMID:23257942

  4. Treatment of acute cervical internal carotid artery dissection using the Solitaire FR revascularization device.

    PubMed

    To, Chiu Yuen; Badr, Yaser; Richards, Boyd

    2013-11-01

    During treatment of a right internal carotid artery terminus aneurysm, an acute iatrogenic flow limiting dissection was caused in the cervical internal carotid. The true lumen was catheterized using a Mirage 0.008 microwire over an Excelsior SL-10 microcatheter, which was exchanged for a Marksman microcatheter. A 6 mm × 30 mm Solitaire FR revascularization device was then deployed across the dissection as a salvage technique. PMID:23299103

  5. Endovascular Treatment of Acute Portal Vein Thrombosis After Liver Transplantation in a Child

    SciTech Connect

    Carnevale, Francisco Cesar Borges, Marcus Vinicius; Moreira, Airton Mota; Cerri, Giovanni Guido; Maksoud, Joao Gilberto

    2006-06-15

    Although operative techniques in hepatic transplantation have reduced the time and mortality on waiting lists, the rate of vascular complications associated with these techniques has increased. Stenosis or thrombosis of the portal vein is an infrequent complication, and if present, surgical treatment is considered the traditional management. This article describes a case of acute portal vein thrombosis after liver transplantation from a living donor to a child managed by percutaneous techniques.

  6. Extended-release morphine sulfate in treatment of severe acute and chronic pain

    PubMed Central

    Balch, Robert J; Trescot, Andrea

    2010-01-01

    Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolism, pharmacodynamics, formulations, and efficacy of the currently available extended-release morphine medications. PMID:21197323

  7. Relationship Between Depressive State and Treatment Characteristics of Acute Cervical Spinal Cord Injury in Japan

    PubMed Central

    Matsuda, Yasufumi; Kubo, Tatsuhiko; Fujino, Yoshihisa; Matsuda, Shinya; Wada, Futoshi; Sugita, Atsuko

    2016-01-01

    Background Few studies have assessed whether treatment of acute cervical spinal cord injury (SCI) patients contributes to depression. Methods Using an administrative database, we assessed patients for whom the diagnosis was unspecified injuries of cervical spinal cord (International Classification of Diseases and Injuries-10th (ICD-10) code; S14.1). We categorized patients with codes for depressive episode (ICD-10 code; F32) or recurrent depressive disorder (F33), or those prescribed antidepressants (tricyclic, tetracyclic, Selective Serotonin Reuptake Inhibitors, Serotonin Noradrenaline Reuptake Inhibitors, Trazodone, Sulpiride, or Mirtazapine) as having a depressive state. We compared the rate of each acute treatment between the depressive state group and the non-depressive state group using chi-square tests, and a multiple logistic regression model was used to identify the association between the acute treatment and depressive state. Results There were 151 patients who were judged to be in a depressive state, and the other 2115 patients were categorized into the non-depressive state group. Intervention of intravenous anesthesia, tracheostomy, artificial respiration, and gastrostomy had a significant positive correlation with depressive state. Multiple logistic regression analysis showed that tracheostomy (odds ratio [OR] 2.18; 95% confidence interval [CI], 1.09–4.38) and artificial respiration (OR 2.28; 95% CI, 1.32–3.93) were significantly associated with depressive state, and men had a 36% reduction in the risk of depressive state compared with women (OR 0.64; 95% CI, 0.44–0.94), whereas age, wound-treatment, all of the orthopedic procedures, intravenous anesthesia, and gastrostomy were not associated with depressive state. Conclusions These findings suggest that tracheostomy, artificial respiration and female gender in the acute phase after cervical SCI might be associated with the development of depression. PMID:26567604

  8. Oral idarubicin plus cytosine arabinoside in the treatment of acute non lymphoblastic leukemia in elderly patients.

    PubMed

    Pagano, L; Sica, S; Marra, R; Voso, M T; Storti, S; Di Mario, A; Leone, G

    1991-01-01

    Eighteen acute nonlymphoblastic leukemia patients greater than 60 yr., 12 at diagnosis and 6 in first relapse, were treated with the association of oral Idarubicin and subcutaneous Aracytin. One patient was not evaluable. Eight out of 17 patients achieved complete remission (47%), 4 patients died in induction and 5 proved resistant to treatments. Mucocutaneous and gastrointestinal toxicity was mild. The most frequent extra-hematological complications were infections. We observed an important hepatic toxicity in 1 case. PMID:1820991

  9. Calcium flux and metabolism in the pigeon heart following doxorubicin treatment: an acute study

    SciTech Connect

    Revis, N.

    1981-01-01

    The present studies were performed to determine in vivo the initial and secondary acute effects of doxorubicin on the influx of calcium into myocardial cells. Studies are also described showing the effect of doxorubicin on a calcium-activated neutral protease from cardiac tissue. These latter studies were performed in an attempt to explain the loss of myofibrilular structures in myocardial cells following doxorubicin treatment.

  10. Acute visceral cysticercosis by Taenia hydatigena in lambs and treatment with praziquantel.

    PubMed

    Scala, A; Urrai, G; Varcasia, A; Nicolussi, P; Mulas, M; Goddi, L; Pipia, A P; Sanna, G; Genchi, M; Bandino, E

    2016-01-01

    An acute outbreak of Taenia hydatigena cysticercosis, causing mortality in 5 of 21 (23.8%) female lambs, is reported. Gross post-mortem examinations and histology showed Cysticercus tenuicollis as the cause of death. Biochemical parameters in infected lambs confirmed severe hepatitis. Praziquantel, given once at 15 mg/kg body weight (bw), was administered and a dramatic improvement in the clinical condition and biochemical parameters was observed up to 30 days following treatment. PMID:25120032

  11. [Current state of knowledge and developments in the prophylaxis and acute treatment of migraine].

    PubMed

    Schriever, J; Bühlen, M; Broich, K

    2014-08-01

    For the acute treatment of the headache phase of a migraine attack, a variety of different pharmacotherapeutic treatment options exist. These range from nonspecifically acting non-opioid analgesics (e.g., paracetamol) and nonsteroidal anti-inflammatory substances (e.g., acetylsalicylic acid, ibuprofen, naproxen, diclofenac) to agents specifically interfering with the serotonin system (ergot alkaloids such as ergotamine and its derivatives, triptans). In patients with significant emesis co-occurring during an attack, additional antiemetics such as metoclopramide or domperidone may be administered. In migraine prophylaxis, largely divergent agents, e.g., β-adrenoceptor antagonists, Ca-antagonists, or anticonvulsants, are commonly used. The diversity of these compounds may help the treating physician to tailor prophylactic treatment to the patient's individual needs. The treatment success of the individual patient is difficult to predict both in acute and prophylactic migraine treatment. Apart from contraindications or associated side effects of a particular substance, the individual patient's response to treatment is therefore a major determinant in selecting the suitable medication. PMID:25028243

  12. Interventional Treatment of Abdominal Compartment Syndrome during Severe Acute Pancreatitis: Current Status and Historical Perspective

    PubMed Central

    Radenkovic, Dejan V.; Johnson, Colin D.; Milic, Natasa; Gregoric, Pavle; Ivancevic, Nenad; Bezmarevic, Mihailo; Bilanovic, Dragoljub; Cijan, Vladimir; Antic, Andrija; Bajec, Djordje

    2016-01-01

    Abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) is a marker of severe disease. It occurs as combination of inflammation of retroperitoneum, visceral edema, ascites, acute peripancreatic fluid collections, paralytic ileus, and aggressive fluid resuscitation. The frequency of ACS in SAP may be rising due to more aggressive fluid resuscitation, a trend towards conservative treatment, and attempts to use a minimally invasive approach. There remains uncertainty about the most appropriate surgical technique for the treatment of ACS in SAP. Some unresolved questions remain including medical treatment, indications, timing, and interventional techniques. This review will focus on interventional treatment of this serious condition. First line therapy is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Midline laparostomy seems to be method of choice. Since it carries significant morbidity we need randomized studies to establish firm advantages over other described techniques. After ACS resolves efforts should be made to achieve early primary fascia closure. Additional data are necessary to resolve uncertainties regarding ideal timing and indication for operative treatment. PMID:26839539

  13. An observational efficacy and safety analysis of the treatment of acute invasive aspergillosis using voriconazole.

    PubMed

    Jacobs, F; Selleslag, D; Aoun, M; Sonet, A; Gadisseur, A

    2012-06-01

    The purpose of this study was to evaluate efficacy and safety of voriconazole in patients with acute invasive aspergillosis (IA) in a real-life, clinical setting. This was a multicenter observational study in adult patients treated with voriconazole for invasive mycosis. The study evaluated clinical response, mortality, use of other licensed antifungal therapy (OLAT), and treatment duration. This sub-analysis evaluated treatment and outcome data specifically from adult patients with proven/probable IA, while safety data were assessed in patients with proven/probable/possible IA. Of the 141 patients enrolled, 113 were adults with proven/probable IA and six had possible IA. Voriconazole treatment duration ranged from 1 to 183 days (median, 49.5 days). Voriconazole was used exclusively in 64% (72/113) of patients and in combination/sequentially with OLAT in 36%. Overall successful treatment response was 50% (57/113 patients). Twelve percent (14/113) of patients were switched to OLAT, either because of insufficient response (four patients) or for safety reasons (10 patients). Overall and attributable (entirely or partially due to fungal infection) mortality rates were 52% (59/113) and 17%, respectively. Treatment-related adverse events were reported for 18% (22/119) of patients. This observational study confirms the results of previous clinical trials demonstrating voriconazole as an effective and safe agent for treatment of confirmed acute IA. PMID:21971820

  14. Interventional Treatment of Abdominal Compartment Syndrome during Severe Acute Pancreatitis: Current Status and Historical Perspective.

    PubMed

    Radenkovic, Dejan V; Johnson, Colin D; Milic, Natasa; Gregoric, Pavle; Ivancevic, Nenad; Bezmarevic, Mihailo; Bilanovic, Dragoljub; Cijan, Vladimir; Antic, Andrija; Bajec, Djordje

    2016-01-01

    Abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) is a marker of severe disease. It occurs as combination of inflammation of retroperitoneum, visceral edema, ascites, acute peripancreatic fluid collections, paralytic ileus, and aggressive fluid resuscitation. The frequency of ACS in SAP may be rising due to more aggressive fluid resuscitation, a trend towards conservative treatment, and attempts to use a minimally invasive approach. There remains uncertainty about the most appropriate surgical technique for the treatment of ACS in SAP. Some unresolved questions remain including medical treatment, indications, timing, and interventional techniques. This review will focus on interventional treatment of this serious condition. First line therapy is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Midline laparostomy seems to be method of choice. Since it carries significant morbidity we need randomized studies to establish firm advantages over other described techniques. After ACS resolves efforts should be made to achieve early primary fascia closure. Additional data are necessary to resolve uncertainties regarding ideal timing and indication for operative treatment. PMID:26839539

  15. Disseminated intravascular coagulation observed following treatment with gemtuzumab ozogamicin for relapsed/refractory acute promyelocytic leukemia

    PubMed Central

    AZUMA, YOSHIKO; NAKAYA, AYA; HOTTA, MASAAKI; FUJITA, SHINYA; TSUBOKURA, YUKIE; YOSHIMURA, HIDEAKI; SATAKE, ATSUSHI; ISHII, KAZUYOSHI; ITO, TOMOKI; NOMURA, SHOSAKU

    2016-01-01

    Gemtuzumab ozogamicin (GO) is a recombinant humanized immunoglobulin G4 anti-cluster of differentiation (CD)33 monoclonal antibody conjugated to N-acetyl-γ calicheamicin dimethylhydrazide, a naturally potent antibiotic. It has been introduced for the treatment of acute promyelocytic leukemia (APL), since large quantities of CD33 are commonly expressed on the surface of APL cells. The present study reported two cases with prominent disseminated intravascular coagulation (DIC), which was transiently observed following treatment with GO with relapsed/refractory APL. Very limited information exists regarding DIC occurring following GO, and its mechanism remains to be elucidated. In the present study, recombinant human soluble thrombomodulin was used for DIC treatment, and the patients recovered promptly. Since DIC is the most serious adverse event associated with GO treatment, elucidation of its mechanism and establishment of a treatment strategy are warranted. PMID:27330760

  16. Measuring patient outcomes and making the transition from acute to maintenance treatment for bipolar depression.

    PubMed

    Manning, J Sloan

    2015-12-01

    Patients with bipolar disorder require diligent management involving psychoeducation, a strong therapeutic alliance, and ongoing monitoring with rating scales to achieve the best outcomes. Clinicians should monitor symptom response, functioning, and quality of life to determine if treatment needs to be be adjusted. Assessing adverse effects must be done regularly to improve treatment adherence. Because effective acute phase treatments are often continued in maintenance treatment, clinicians must find the right balance of efficacy and tolerability for long-term success. The FDA has approved 7 agents for maintenance treatment of bipolar disorder. Because of the high risk of recurrent depressive episodes, clinicians should be aware of which agents are more effective for reducing manic or depressive relapses. PMID:26717538

  17. Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections

    PubMed Central

    Mitra, Subhashis; Saeed, Usman; Havlichek, Daniel H; Stein, Gary E

    2015-01-01

    Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA. PMID:26185459

  18. [IDA-FLAG regimen in treatment of patients with refractory or relapsed acute leukemia].

    PubMed

    Qian, Si-Xuan; Li, Jian-Yong; Wu, Han-Xin; Zhang, Run; Hong, Ming; Xu, Wei; Qiu, Hong-Xia

    2009-04-01

    The objective of this study was to evaluate the efficacy and toxicity of the fludarabine combination with high-dose cytarabine (Ara C), idarubicin and granulocyte colony-stimulating factor (G-CSF) (IDA-FLAG regimen) in treatment of refractory/relapsed acute leukemia (AL) patients. 4 patients were male aged from 32 to 44 years, consisted of 3 cases of acute myeloid leukaemia (AML) and 1 cases of acute lymphocytic leukaemia (ALL). All the patients were treated with idarubicin (10 - 12 mg/m(2)/d, days 1 to 3), fludarabine (50 mg/d, days 1 to 5), cytarabine (2 g/m(2)/d, days 1 to 5) and granulocyte colony-stimulating factor (G-CSF, 300 microg/d, days 0 to 5). The results showed that after one course of induction therapy, 4 patients all achieved complete remission (CR), in which 2 patients were in continuous CR after a follow-up of 3 and 4 months; 1 patient relapsed after 10 months and another one patient died of thrombotic thrombocytopenic purpura at 4 months after allogeneic peripheral blood stem cell transplantation. Myelosuppression and infections due to neutropenia were the most frequent adverse effects, severe nonhematologic toxicity and the early death were not observed in these patients. In conclusion, the IDA-FLAG regimen is effective in treatment of patients with refractory and relapsed AL, the adverse effects from this regimen were well tolerated by patients, which gains time for further treatment. PMID:19379589

  19. Home treatment of patients with small to medium sized acute pulmonary embolism.

    PubMed

    Elf, J E; Jögi, J; Bajc, M

    2015-02-01

    Most patients with acute pulmonary embolism (PE) are still treated as inpatients. This is a retrospective cohort study of patients with acute PE, diagnosed using V/P SPECT between 2007 and 2011. Patients were treated at home if they were hemodynamically stable, did not require oxygen or parenteral analgetics, had no contraindications to anticoagulant treatment and V/P SPECT showed an extension of the PE of less than 40%. The aim of the study was to evaluate the efficacy and safety of home treatment with our algorithm. During the study period 416 outpatients were diagnosed with acute symptomatic PE of whom in total 260 (62.5%) were discharged home from the emergency unit and another 47 (11%) within 24 h from admission. During 3 months follow-up one (0.3%) patient had a recurrent thrombotic event. Eleven (3.6%) patients had a major or clinically relevant bleed and the overall mortality was 2% (n = 6). There were no PE-related mortality. Home treatment should be considered and is safe in the majority of hemodynamically stable outpatients with small to medium size PE, quantified using V/P SPECT. PMID:24942995

  20. Efficacy of enrofloxacin in the treatment of naturally occurring acute clinical Escherichia coli mastitis.

    PubMed

    Suojala, L; Simojoki, H; Mustonen, K; Kaartinen, L; Pyörälä, S

    2010-05-01

    The efficacy of the combination of systemic enrofloxacin (5mg/kg twice with a 24-h interval, first dose i.v., second dose s.c.) and the nonsteroidal antiinflammatory agent ketoprofen (3mg/kg i.m. or 4 mg/kg per os daily for 1 to 3 d) treatment was compared with antiinflammatory treatment only in dairy cows with naturally occurring acute clinical Escherichia coli mastitis. A total of 132 cows with acute clinical mastitis and with confirmed growth of E. coli in a pretreatment milk sample were randomly allocated to 1 of 2 treatment groups. Response to treatment was evaluated clinically and by bacteriological culturing and determination of N-acetyl-beta-d-glucosaminidase (NAGase) activity on d 2 and 21 posttreatment. Enrofloxacin treatment did not increase bacteriological (90.5% of treated vs. 86.8% of nontreated cured) or clinical cure (46.7% of treated vs. 57.1% of nontreated cured), cow survival (95.3% of treated vs. 92.7% of nontreated), or quarter milk production assessed 21 d posttreatment (21.8 vs. 29.3% return to preinfection level for nontreated cows), nor did it decrease mammary gland tissue damage estimated using determination of milk NAGase activity (24.0+/-0.3 vs. 18.3+/-1.3 pmol of 4-methylumbelliferone per min per microL for nontreated cows). Treatment did not influence the number of study cows remaining in the herd after 6 mo (71.9% of treated vs. 80.6% of nontreated). The only significant effects of enrofloxacin were enhancing the bacteriological cure (odds ratio=3.32 for treated cows) and decreasing the clinical cure (odds ratio=0.05 for treated cows) on d 2 posttreatment. Our results did not support the use of enrofloxacin to treat acute clinical E. coli mastitis. PMID:20412909

  1. 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

  2. Assessing acute toxicities of pre- and post-treatment industrial wastewaters with Hydra attenuata: A comparative study of acute toxicity with the fathead minnow, Pimephales promelas

    SciTech Connect

    Fu, L.J.; Staples, R.E.; Stahl, R.G. Jr. . Haskell Lab. for Toxicology and Industrial Medicine)

    1994-04-01

    This study was undertaken to (a) determine wastewater treatment effectiveness using two freshwater organisms, (b) compare acute toxicity results from the two species exposed to the wastewaters, and (c) link acute and potential developmental toxicity of wastewaters in one organism. The acute toxicities of several pretreatment and post-treatment industrial waste-water samples wee evaluated with adult Hydra attenuata and fathead minnows. The acute LC50s agreed closely when results in Hydra attenuata were compared with those from fathead minnow tests. Acute LC50s ranged from 3 to >100% of samples with hydra, and from 1.0 to >100% of sample with fathead minnows. The results provided strong evidence of treatment effectiveness because toxicity decreased with progressive stages of treatment. Previously the Hydra Developmental Toxicity Assay was used as a prescreen mainly for in vitro assessment of developmental toxicity with pure compounds and to prioritized toxicants according to selective toxicity to the developing embryo. Recently the authors modified the assay for testing natural waters and wastewaters; hence, some of the wastewater samples also were tested for their developmental toxicity. In this case, the relative selective toxicity of these wastewater samples ranged from 0.7 to 2.1, indicating that no sample was uniquely toxic to the developing embryo, although acute toxicity was manifested. Overall, their results indicate the Hydra Assay functions appropriately in assessments of acute and developmental toxicity of industrial wastewaters and may be a simple and useful tool in a battery of tests for broader scale detection of environmental hazards.

  3. Acute Dystonia Following a Switch in Treatment from Atomoxetine to Low-dose Aripiprazole.

    PubMed

    Başay, Ömer; Basay, Burge Kabukcu; Öztürk, Önder; Yüncü, Zeki

    2016-05-31

    The present report describes the cases of a 17-year-old male patient and a 13-year-old female patient who developed acute dystonia following the administration of low-dose aripiprazole (5 mg/day) after the cessation of atomoxetine treatment. Although aripiprazole-induced dystonia has been previously reported in the literature, it is rare, and most of these cases were associated with doses higher than 5 mg/day. Furthermore, both of the patients in the present study discontinued atomoxetine prior to the initiation of aripiprazole treatment; thus, this report also discussed the possible mechanisms underlying the manifestation of dystonia from the perspective of neurotransmitter activity. PMID:27121436

  4. [The prevention and treatment of suppurative-septic complications in patients with acute appendicitis].

    PubMed

    Korotkiĭ, V N; Geleskul, V F; Kolosovich, I V; Butyrin, S A

    1993-01-01

    In the experiment on mongrel dogs, the absorption of indigo carmine dye after its retroperitoneal administration with 10% dimexide solution into the lymphatic and venous systems was studied. More rapid delivery of a dye into the portal system, including the cases with portal hypertension, and into the lymphatic system was established. A method for retroperitoneal administration of antibiotics with 10% dimexide solution for prevention and treatment of purulent-septic complications in patients with acute appendicitis has been developed. The method was used in 120 patients, the result of treatment is good. PMID:10912051

  5. Lack of acute toxicity associated with a multimodality treatment of stage III ovarian epithelial carcinoma

    SciTech Connect

    Belch, R.Z.; Coughlin, C.T.; Cooney, L.C.; Forcier, R.J.; Maurer, L.H. )

    1990-04-01

    Eleven patients with advanced stage III ovarian epithelial carcinoma were treated primarily according to an aggressive multimodality plan utilizing cytoreductive surgery, chemotherapy (high-dose cisplatin and Cytoxan), and consolidative radiation therapy (abdominopelvic bath plus pelvic boost). The treatment was tolerated remarkably well. There was no evidence of progressive disease during treatment, and all patients showed a positive response. There was a notable lack of significant acute morbidity, with the exception of a severe symptomatic peripheral neuropathy associated with cisplatin doses of 200 mg/m2. This was not evident with doses of cisplatin up to 150 mg/m2.

  6. Acute Dystonia Following a Switch in Treatment from Atomoxetine to Low-dose Aripiprazole

    PubMed Central

    Başay, Ömer; Basay, Burge Kabukcu; Öztürk, Önder; Yüncü, Zeki

    2016-01-01

    The present report describes the cases of a 17-year-old male patient and a 13-year-old female patient who developed acute dystonia following the administration of low-dose aripiprazole (5 mg/day) after the cessation of atomoxetine treatment. Although aripiprazole-induced dystonia has been previously reported in the literature, it is rare, and most of these cases were associated with doses higher than 5 mg/day. Furthermore, both of the patients in the present study discontinued atomoxetine prior to the initiation of aripiprazole treatment; thus, this report also discussed the possible mechanisms underlying the manifestation of dystonia from the perspective of neurotransmitter activity. PMID:27121436

  7. Treatment strategies in the left main coronary artery disease associated with acute coronary syndromes.

    PubMed

    Karabulut, Ahmet; Cakmak, Mahmut

    2015-10-01

    Significant left main coronary artery (LMCA) stenosis is not rare and reported 3 to 10% of patients undergoing coronary angiography. Unprotected LMCA intervention is a still clinical challenge and surgery is still going to be a traditional management method in many cardiac centers. With a presentation of drug eluting stent (DES), extensive use of IVUS and skilled operators, number of such interventions increased rapidly which lead to change in recommendation in the guidelines regarding LMCA procedures in the stable angina (Class 2a recommendation for ostial and shaft lesion and class 2b recommendation for distal bifurcation lesion). However, there was not clear consensus about the management of unprotected LMCA lesion associated with acute myocardial infarction (MI) with a LMCA culprit lesion itself or distinct culprit lesion of other major coronary arteries. Surgery could be preferred as an obligatory management strategy even in the high risk patients. With this review, we aimed to demonstrate treatment strategies of LMCA disease associated with acute coronary syndrome, particularly acute myocardial infarction (MI). In addition, we presented a short case series with LMCA lesion and ST elevated acute MI in which culprit lesion placed either in the left anterior descending artery or circumflex artery. We reviewed the current medical literature and propose simple algorithm for management. PMID:26557745

  8. Dexamethasone treatment for acute bacterial meningitis: how strong is the evidence for routine use?

    PubMed Central

    Prasad, K; Haines, T

    1995-01-01

    A methodological appraisal of the published randomised controlled trials on the use of dexamethasone as an adjunct treatment in acute bacterial meningitis was carried out to examine whether the available evidence is strong enough to support the routine use of the drug. Studies were eligible for inclusion if they were published in indexed journals after 1966, written in English, and were randomised controlled trials with dexamethasone as adjunct to antimicrobials in patients with acute bacterial meningitis. All studies were extracted and their adherence to eight methodological principles was graded as adequate, inadequate, or unclear. A sensitivity analysis was done to examine the robustness of the conclusions. Seven studies met the eligibility criteria. No report adhered to all the principles. Major threats to validity of the conclusions included potential bias in analysis in all the studies, and lack of adjustment for baseline imbalances in four. Inadequate reporting of adverse effects hindered risk-benefit analysis. Sensitivity analysis showed that the numbers of patients withdrawn from analysis were enough to invalidate the conclusions. It is concluded that the available evidence is not strong enough to support a routine use of dexamethasone in acute bacterial meningitis. Further research is needed to determine the effect of a policy to use dexamethasone early in the management of suspected acute bacterial meningitis. Future studies should adopt a pragmatic approach, be methodologically rigorous, and meticulously measure the risk as well as the benefit of this policy. PMID:7608706

  9. Physiology in Medicine: A physiologic approach to prevention and treatment of acute high-altitude illnesses.

    PubMed

    Luks, Andrew M

    2015-03-01

    With the growing interest in adventure travel and the increasing ease and affordability of air, rail, and road-based transportation, increasing numbers of individuals are traveling to high altitude. The decline in barometric pressure and ambient oxygen tensions in this environment trigger a series of physiologic responses across organ systems and over a varying time frame that help the individual acclimatize to the low oxygen conditions but occasionally lead to maladaptive responses and one or several forms of acute altitude illness. The goal of this Physiology in Medicine article is to provide information that providers can use when counseling patients who present to primary care or travel medicine clinics seeking advice about how to prevent these problems. After discussing the primary physiologic responses to acute hypoxia from the organ to the molecular level in normal individuals, the review describes the main forms of acute altitude illness--acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema--and the basic approaches to their prevention and treatment of these problems, with an emphasis throughout on the physiologic basis for the development of these illnesses and their management. PMID:25539941

  10. The antimicrobial armamentarium: evaluating current and future treatment options.

    PubMed

    Bosso, John A

    2005-10-01

    The development and introduction of new antibiotics has, unfortunately, not kept pace with the development of bacterial resistance, and the need for new agents is becoming acute. Although some currently marketed agents remain valuable tools in the treatment of infectious diseases, few new drugs have reached the market in the last decade. In recent years, antibiotics with activity against certain problematic resistant bacteria such as methicillin-resistant Staphylococcus aureus, including linezolid and daptomycin, have been approved for clinical practice. Recently, tigecycline, a minocycline derivative, received approval by the United States Food and Drug Administration for treatment of complicated skin and skin structure and intraabdominal infections; the agent is also active against a variety of multidrug-resistant bacteria. Of the other agents in phase III development, ceftobiprole--a cephalosporin, and faropenem and doripenem--both carbapenems, have wide antibacterial spectra. Antimicrobial agents in the pipeline with marked gram-positive activity include dalbavancin, telavancin, and oritavancin. PMID:16178676

  11. Emergency department treatment of adults with acute asthma exacerbations: effect on exhaled nitric oxide levels.

    PubMed

    Silverberg, Jonathan I; Rodenas, Mario; Sinert, Richard; Joks, Rauno

    2012-01-01

    Measurement of exhaled nitric oxide levels (eNO) from asthmatic patients is a noninvasive marker of airway inflammation in both adults and children and has been used as an outpatient measure of asthma control. We examined eNO in acute asthma exacerbations and how it is affected by treatment in the emergency department (ED) setting. Both eNO and peak expiratory flow (PEF) rate were measured at arrival and before discharge for adult asthmatic subjects (n = 28) treated for acute exacerbations in the ED at Kings County Hospital Center during spring and fall pollen seasons. Total serum Immunoglobulin E (IgE), peripheral blood leukocyte numbers, and tobacco smoking history were determined. Routine ED treatment included oral prednisone at 60 mg and inhalation of nebulized albuterol and ipratropium. Both PEF (p = 0.0005) and eNO (p < 0.0001) increased after treatment of subjects. Initial eNO was associated with age (p = 0.0004), absolute eosinophil count (p = 0.003), Asthma Control Test (p = 0.004), and Asthma Quality of Life Questionnaire (p = 0.04). Change in pre- versus posttreatment eNO (ΔeNO) was associated with change in PEF (ΔPEF; p < 0.0001). Initial PEF was associated with oxygen saturation (p < 0.0001). ΔPEF was associated with serum IgE levels. ED visit duration was associated with initial PEF (p = 0.0004), ΔeNO (p = 0.004), and number of albuterol treatments (p = 0.001). These associations remained significant in multivariate models that controlled for demographic factors, asthma control, smoking, and measures of inflammation and ventilation. eNO levels increase after ED treatment of acute asthma exacerbations in adults. Improved ventilation may allow for more accurate measurement of NO produced in inflamed airways. PMID:23394510

  12. Dynamics of Plasmodium falciparum Parasitemia Regarding Combined Treatment Regimens for Acute Uncomplicated Malaria, Antioquia, Colombia

    PubMed Central

    Álvarez, Gonzalo; Tobón, Alberto; Piñeros, Juan-Gabriel; Ríos, Alexandra; Blair, Silvia

    2010-01-01

    Selecting suitable anti-malarial treatment represents one of the best tools for reducing morbidity and mortality caused by this disease. Sexual and asexual parasite dynamics were thus evaluated in patients involved in antimalarial drug efficacy studies by using combined treatment with and without artemisinin derivatives for treating uncomplicated acute Plasmodium falciparum malaria in Antioquia, Colombia. All treatment doses were supervised and administered according to patients' weight; sexual and asexual parasitemia were evaluated during 28- or 42-days follow-up in 468 patients. Artemisinin-based combination therapy showed greater parasiticidal ability, showing a mean asexual parasitemia survival rate of one day and mean gametocyte survival rate of 1–2 days. Sexual and asexual parasitemias were eliminated more quickly and effectively in the group receiving artemisinin-based combination therapy. Adding 45 mg of primaquine to treatment with artesunate and mefloquine reduced gametocyte and asexual parasite survival by one day. PMID:20595483

  13. Neuroprotective effects of minocycline against in vitro and in vivo retinal ganglion cell damage.

    PubMed

    Shimazawa, Masamitsu; Yamashima, Tetsumori; Agarwal, Neeraj; Hara, Hideaki

    2005-08-16

    The purpose of this study was to determine whether minocycline, a semi-synthetic tetracycline derivative, reduces (a) the in vitro neuronal damage occurring after serum deprivation in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) and/or (b) the in vivo retinal damage induced by N-methyl-D-aspartate (NMDA) intravitreal injection in mice. In addition, we examined minocycline's putative mechanisms of action against oxidative stress and endoplasmic reticulum (ER) stress. In vitro, retinal damage was induced by 24-h serum deprivation, and cell viability was measured by Hoechst 33342 staining or resazurin reduction assay. In cultures of RGC-5 cells maintained in serum-free medium for up to 24 h, the number of cells undergoing cell death was reduced by minocycline (0.2-20 microM). Serum deprivation resulted in increased oxidative stress, as revealed by an increase in the fluorescence intensity for 5-(and-6)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA), a reactive oxygen species (ROS) indicator. Minocycline at 2 and 20 microM inhibited this ROS production. However, even at 20 microM minocycline did not inhibit the retinal damage induced by tunicamycin (an ER stress inducer). Furthermore, in mice in vivo minocycline at 90 mg/kg intraperitoneally administered 60 min before an NMDA intravitreal injection reduced the NMDA-induced retinal damage. These findings indicate that minocycline has neuroprotective effects against in vitro and in vivo retinal damage, and that an inhibitory effect on ROS production may contribute to the underlying mechanisms. PMID:16051195

  14. [A case of chronic hepatitis C with pancreas divisum and acute pancreatitis during combination treatment with telaprevir/peginterferon/ribavirin].

    PubMed

    Morio, Reona; Imamura, Michio; Fukuhara, Takayuki; Kan, Hiromi; Fujino, Hatsue; Kawaoka, Tomokazu; Hiramatsu, Akira; Aikata, Hiroshi; Sasaki, Tamito; Chayama, Kazuaki

    2014-10-01

    A 47-year-old man developed acute pancreatitis during combination treatment with telaprevir/peginterferon/ribavirin for chronic hepatitis C. Cessation of telaprevir, fasting, and gabexate mesilate improved the pancreatitis. Although peginterferon and ribavirin treatment was continued, there was no recurrence of the pancreatitis. Endoscopic retrograde cholangiopancreatography incidentally showed a pancreas divisum. We definitively diagnosed drug-induced acute pancreatitis due to telaprevir. PMID:25283229

  15. Trimethoprim-sulfamethoxazole v. amoxicillin in the treatment of acute otitis media.

    PubMed Central

    Feldman, W; Momy, J; Dulberg, C

    1988-01-01

    Although amoxicillin has long been the preferred drug for treatment of acute otitis media, resistant strains of two relatively common causal organisms have emerged, prompting a search for other antibiotics. We performed a randomized double-blind trial comparing amoxicillin and trimethoprim-sulfamethoxazole in 221 children in whom acute otitis media was diagnosed in an outpatient setting. Diagnosis was on the basis of symptoms, otoscopic examination and acoustic reflectometry. No culture specimens were taken. A research nurse, using the same methods, evaluated patients in a follow-up home visit at around 14 days and measured compliance by examination of the medicine bottle. Equal proportions of children in the two groups were cured or improved (88% and 87%). Therapeutic efficacy was related to compliance in both groups, and there were few side effects in either group. This study had statistical power of 80% to detect a difference of 15%. We conclude that trimethoprim-sulfamethoxazole can be considered a first-line antibiotic in the treatment of acute otitis media. PMID:3052769

  16. Nd:YAG Laser Irradiation of the Tooth Root Surface Inhibits Demineralization and Root Surface Softening Caused by Minocycline Application

    PubMed Central

    Watanabe, Tomohisa; Mitani, Akio; Ting, Chun-Chan; Osawa, Kazuhiro; Nagahara, Ayako; Satoh, Sohta; Fujimura, Takeki; Takahashi, Shinko; Iwamura, Yuki; Murakami, Taeko; Noguchi, Toshihide

    2013-01-01

    Abstract Objective: The aim of this study was to investigate the effect of laser irradiation on root surface demineralization caused by local drug delivery systems (DDS), and to evaluate the effect of sealing on drug retention. Background data: The duration of supportive periodontal treatment (SPT) has increased with increasing life expectancy. Repeated root planing and DDS application during SPT should be reconsidered with regard to their effects on the root surface. Methods: Extracted human teeth were collected, cut into 3×3×2 mm root dentin specimens, and divided randomly into eight groups with various combinations of Nd:YAG laser power (0, 0.5, 1, and 2 W), with and without DDS (minocycline HCl). Specimen microhardness and calcium (Ca) solubility were measured after treatment. The specimens (control and laser and DDS groups) were examined by scanning electron microscopy. Forty SPT patients were recruited, to assess the effect of periodontal pocket sealing on drug retention. Results: Laser irradiation increased the microhardness of root specimens in an energy-dependent manner. Calcium solubilities decreased from the 0 W+DDS group to the 2.0 W+DDS group. The mean Ca solubilities in the 1.0 W+DDS and 2.0 W+DDS groups were significantly lower than in the 0 W+DDS group (p<0.01, p<0.001, respectively). Laser irradiation counteracted the softening effect of DDS. Morphologic change was observed in the 2W+DDS group; however, no morphologic changes were observed in the control and the 1W+DDS groups. The mean concentration of minocycline in the periodontal pocket 24 h after application was 252.79±67.50 μg/mL.Conclusions: Laser irradiation of the root surface inhibited the softening and decalcification caused by minocycline HCl. Sealing the periodontal pockets effectively improved drug retention. These results suggest that the combination of laser irradiation and DDS could benefit patients receiving repeated SPT. PMID:24219120

  17. Bioelectrical Impedance Measurement for Predicting Treatment Outcome in Patients With Newly Diagnosed Acute Leukemia

    ClinicalTrials.gov

    2015-09-22

    Acute Undifferentiated Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

    PubMed Central

    Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

    2012-01-01

    Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

  19. Minocycline modulates neuroprotective effect of hesperidin against quinolinic acid induced Huntington's disease like symptoms in rats: behavioral, biochemical, cellular and histological evidences.

    PubMed

    Kumar, Anil; Chaudhary, Tanya; Mishra, Jitendriya

    2013-11-15

    Emerging evidences indicate hesperidin, a citrus flavanone, attenuates neurodegenerative processes and related complications. Besides its anti-oxidant properties, the other probable mechanisms which underpin its neuroprotective potential are still not clear. In light of emerging role of flavonoids in modulating oxidative stress and neuro-inflammation, the study has been designed to explore the possible neuroprotective effect of hesperidin and its combination with minocycline (microglial inhibitor), against quinolinic acid (QA) induced Huntington's disease (HD) like symptoms in rats. Unilateral intrastriatal administration of QA (300 nmol/4 µl) significantly reduced body weight, impaired behavior (locomotor activity, beam balance and memory performance), caused oxidative damage (increased lipid peroxidation, nitrite concentration, depleted super oxide dismutase and reduced glutathione), demonstrated mitochondrial dysfunction (decreased Complex-I, II, III, and IV activities), increased striatal lesion volume and altered the levels of TNF-α, caspase-3 as well as BDNF expression, as compared to sham group. Meanwhile, chronic hesperidin (100mg/kg, p.o.) and minocycline (25mg/kg, p.o.) treatment for 21 days significantly attenuated the behavioral, biochemical and cellular alterations as compared to QA treated (control) animals, whereas hesperidin (50mg/kg, p.o.) treatment was found to be non-significant. However, treatment of hesperidin (50mg/kg) in combination with minocycline (25mg/kg) potentiated their neuroprotective effect, which was significant as compared to their effects per se in QA treated animals. Taken altogether, the results of the present study suggest a possible interplay of microglial modulation and anti-oxidant effect in neuroprotective potential of hesperidin against QA induced HD like symptoms in rats. PMID:24211676

  20. Gelatin-coated Gold Nanoparticles as Carriers of FLT3 Inhibitors for Acute Myeloid Leukemia Treatment.

    PubMed

    Suarasan, Sorina; Simon, Timea; Boca, Sanda; Tomuleasa, Ciprian; Astilean, Simion

    2016-06-01

    This study presents the design of a gold nanoparticle (AuNPs)-drug system with improved efficiency for the treatment of acute myeloid leukemia. The system is based on four different FLT3 inhibitors, namely midostaurin, sorafenib, lestaurtinib, and quizartinib, which were independently loaded onto gelatin-coated gold nanoparticles. Detailed investigation of the physicochemical properties of the formed complexes lead to the selection of quizartinib-loaded AuNPs for the in vitro evaluation of the biological effects of the formed complex against OCI-AML3 acute myeloid leukemia cells. Viability tests by MTT demonstrated that the proposed drug complex has improved efficacy when compared with the drug alone. The obtained results constitute a premise for further in vivo investigation of such drug vehicles based on AuNPs. To the best of our knowledge, this is the first study that investigates the delivery of the above-mentioned FLT3 inhibitors via gelatin-coated gold nanoparticles. PMID:26808072

  1. Controversy and progress for treatment of acute cholangitis after Tokyo Guidelines (TG13).

    PubMed

    Sun, Zhipeng; Zhu, Yubing; Zhu, Bin; Xu, Guangzhong; Zhang, Nengwei

    2016-01-01

    Tokyo Guideline 2013 (TG13) is an international guideline for the diagnosis, classification and treatment of acute cholangitis. Progress and controversy for the two years after TG13 was summarized. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) are both effective imaging tests for common bile duct (CBD) stones. More factors e.g. obesity may be involved in severity assessment. Initiation of broad-spectrum antibiotics addressing the typical Gram-negative enteric bacteria spectrum and early biliary drainage are the mainstay therapeutic options. Early laparoscopic exploration is also an option for stone-related nonsevere acute cholangitis besides endoscopic retrograde cholangial or percutaneous transhepatic cholangial drainage. Surgical biliary drainage should be avoided in severe cholangitis. PMID:26961212

  2. Acute caffeine treatment increases extracellular nucleotide hydrolysis from rat striatal and hippocampal synaptosomes.

    PubMed

    da Silva, Rosane Souza; Bruno, Alessandra Nejar; Battastini, Ana Maria Oliveira; Sarkis, João José Freitas; Lara, Diogo Rizzato; Bonan, Carla Denise

    2003-08-01

    The psychostimulant caffeine promotes behavioral effects such as hyperlocomotion, anxiety, and disruption of sleep by blockade of adenosine receptors. The availability of extracellular adenosine depends on its release by transporters or by the extracellular ATP catabolism performed by the ecto-nucleotidase pathway. This study verified the effect of caffeine on NTPDase 1 (ATP diphosphohydrolase) and 5'-nucleotidase of synaptosomes from hippocampus and striatum of rats. Caffeine and theophylline tested in vitro were unable to modify nucleotide hydrolysis. Caffeine chronically administered in the drinking water at 0.3 g/L or 1 g/L for 14 days failed to affect nucleotide hydrolysis. However, acute administration of caffeine (30 mg/kg, i.p.) produced an enhancement of ATP (50%) and ADP (32%) hydrolysis in synaptosomes of hippocampus and striatum, respectively. This activation of ATP and ADP hydrolysis after acute treatment suggests a compensatory effect to increase adenosine levels and counteract the antagonist action of caffeine. PMID:12834266

  3. Emerging strategies for the treatment of older patients with acute myeloid leukemia.

    PubMed

    Sanz, Miguel A; Iacoboni, Gloria; Montesinos, Pau; Venditti, Adriano

    2016-10-01

    Acute myeloid leukemia (AML) is the most common acute leukemia in adults, and its incidence increases with age. Clinical outcomes in younger patients have improved over the years but, unfortunately, there is little evidence for an equivalent improvement in outcome for older patients. Approximately 50 % of older patients who are able to receive intensive chemotherapy will achieve a complete remission; however, they face a much higher relapse rate than younger patients, and survival rates for this group are low. Therefore, there is an urgent need to improve outcomes in older patients with AML. In this article, we discuss current treatment paradigms for older patients with AML including the challenges faced when determining which patients are eligible for intensive chemotherapy. We then highlight new treatments in development that may benefit this patient group. Cytotoxic agents, hypomethylating agents, molecularly targeted agents, and cell cycle kinase inhibitors are discussed, with a focus on novel agents that have achieved an advanced stage of development. Overall, the treatment of AML in older patients remains a challenge and, whenever possible, treatment should be offered in the context of clinical trials and should be planned with curative intent. PMID:27118541

  4. Reversion by ozone treatment of acute nephrotoxicity induced by cisplatin in rats.

    PubMed Central

    González, Ricardo; Borrego, Aluet; Zamora, Zullyt; Romay, Cheyla; Hernández, Frank; Menéndez, Silvia; Montero, Teresita; Rojas, Enis

    2004-01-01

    BACKGROUND: Ozone therapy has become a useful treatment for pathological processes, in which the damage mediated by reactive oxygen species is involved. Several lines of evidence suggest that cisplatin-induced acute nephrotoxicity is partially mediated by reactive oxygen species AIMS: To analyze the effect of ozone administration after cisplatin-induced acute nephrotoxicity. METHODS: Male Sprague-Dawley rats were treated with five intra-rectal applications of ozone/oxygen mixture at 0.36, 1.1 and 1.8 mg/kg after cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were taken off 5 days after cisplatin treatment. Creatinine was measured in the serum and the activities of antioxidant enzymes and thiobarbituric acid reactive substances and glutathione content were analyzed in renal homogenate. RESULTS: Ozone treatment diminished the increase in serum creatinine levels, the glutathione depletion and also reversed the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric reactive substances was decreased by ozone/oxygen mixture applied after cisplatin. CONCLUSION: Intrarectal applications of ozone reversed the renal pro-oxidant unbalance induced by cisplatin treatment by the way of stimulation to some constituents of antioxidant system in the kidney, and thereby it decreased the renal damage. PMID:15770045

  5. Surgical versus conservative treatment following acute rupture of the Achilles tendon: is there a pedobarographic difference?

    PubMed Central

    Karaaslan, Fatih; Mermerkaya, Musa Uğur; Çıraklı, Alper; Karaoğlu, Sinan; Duygulu, Fuat

    2016-01-01

    Introduction Controversy remains regarding the optimal treatment method and postoperative rehabilitation of acute Achilles tendon ruptures. In this study, pedobarographic assessments of surgical and conservative treatments were compared. Material and methods A prospective assessment was made of 16 patients (eight surgical, eight conservative) and eight healthy controls using a plantar pressure measurement system. Biomechanical gait parameters were obtained using the Footscan dynamic gait analysis system. Kruskal–Wallis and Mann–Whitney U-tests were used for the evaluation of data. Results Nineteen males and five females were assessed, with an average age of 42.0±11.9 years. Follow-up was completed in 16 patients. No statistically significant difference was determined between the two treatment groups with regard to the gait analysis, but a difference was observed with the control group (P<0.001). All patients were able to resume their prior activities after 6 months and regained normal ranges of motion, with a high rate of satisfaction. Most of the patients (75%) were able to return to their pre-injury level of activities. Conclusion Satisfactory results were obtained through conservative treatment of acute ruptures of the Achilles tendon. No significant differences or complications were observed in the group managed conservatively versus the group treated surgically. Further studies including 3D gait analyses and tendon biomechanical research are required to further investigate this issue. PMID:27621640

  6. Bifidobacterium lactis in Treatment of Children with Acute Diarrhea. A Randomized Double Blind Controlled Trial

    PubMed Central

    El-Soud, Neveen Helmy Abou; Said, Reem Nabil; Mosallam, Dalia Sayed; Barakat, Nahla Abdel Moniem; Sabry, Mohamed Ahmed

    2015-01-01

    BACKGROUND: Probiotics are becoming increasingly popular treatment for children diarrhea. Although there are several probiotic strains potentially useful, researches were often limited to certain strains. AIM: To test Bifidobacterium lactis on morbidity of acute diarrhea in children less than 2 years. SUBJECTS AND METHODS: A randomized double-blind controlled clinical trial was conducted in 50 children (1 - 23 months) admitted with acute diarrhea to the Pediatric Hospital, Cairo University and were randomly assigned to receive in addition to usual treatment of diarrhea according to WHO guidelines; one of two treatments either milk formula non-supplemented (n = 25) or supplemented (n = 25) with Bifidobacterium lactis 14.5 × 106 CFU/100 ml daily for one week. Primary outcomes were frequency and duration of diarrhea and hospital stay. Secondary outcomes were duration of fever and vomiting episodes. Safety and tolerance were also recorded. RESULTS: On admission, patients’ characteristics of both groups (50 cases) were similar. For children who received the probiotics for one week; mean duration of diarrhoea was shorter than in controls (3.12 ± 0.92 vs. 4.10 ± 0.94 days) (P = 0.02), number of motions per day was less than in controls (3.96 ± 0.62 vs. 4.46 ± 0.85) (P = 0.04) and discharge from hospital <2 days was more frequent than in controls (72% vs. 44%) (P = 0.048). There was no effect on fever (P = 0.63) or vomiting (P = 0.54). CONCLUSION: Bifidobacterium lactis probiotics in supplemented milk formula decreased significantly frequency, duration of diarrhea, and hospital stay than usual treatment alone in children with acute diarrhea. Additional researches on other uncommon local probiotic species should be encouraged. PMID:27275258

  7. Peptic ulcer hemorrhage combined with acute gout: analyses of treatment in 136 cases.

    PubMed

    Xu, Zhenglei; Zhang, Ru; Zhang, Dingguo; Yao, Jun; Shi, Ruiyue; Tang, Qinghong; Wang, Lisheng

    2015-01-01

    This study aims to compare the safety and curative effect of celecoxib and small-dose methylprednisolone sodium succinate in patients with peptic ulcer hemorrhage combined with acute gout. In this randomized, controlled trial, a total of 136 patients with peptic ulcer hemorrhage combined with acute gout were divided into the celecoxib group or the small-dose methylprednisolone sodium succinate group. These patients underwent gastroscopy hemostasis and proton pump inhibitor (PPI) therapy. Moreover, for the treatment of gout, the patients were administered either celecoxib or small-dose methylprednisolone sodium succinate. Adverse reactions and the visual analogue scale (VAS) score were recorded for the two groups. The difference in adverse reactions between the two groups was not significant (χ(2) = 0.002, P = 0.967). The duration of evident pain relief after the first dose of treatment showed a significant difference between the two groups (t = 13.728, P < 0.01). The VAS scores before treatment were not significantly different between the two groups (t = -1.786, P = 0.076). The VAS scores at 6 h, 2 days, 4 days, 6 days, and 8 days after treatment were significantly different between the two groups (t = 3.239, 6.586, 6.280, 3.737, 3.215; P = 0.002, 0.000, 0.000, 0.000, 0.002, respectively). In cases that receive effective gastroscopy hemostasis and PPI therapy, small-dose methylprednisolone sodium succinate exhibits a greater clinical curative effect for peptic ulcer hemorrhage combined with acute gout as compared to celecoxib, and is associated with greater safety. PMID:26131224

  8. Formulation and Evaluation of Once Daily Minocycline Hydrochloride Extended Release Matrix Tablets

    PubMed Central

    Keny, R. V.; Mankame, S. A.; Lourenco, C. F.

    2009-01-01

    The present study was aimed to develop once daily extended release matrix tablets of minocycline hydrochloride, using hydroxypropylmethylcellulose either alone or in combination with ethyl cellulose as the matrix material in different proportions. The formulated tablets were also compared with a marketed product. The results of the dissolution study indicate that formulations FC-IV, FC-V and FC-VI showed maximum drug release upto 24 h, whereas the marketed product was found to extend the release only up to 14 h. Incase of formulations containing combination of hydroxypropylmethylcellulose and ethyl cellulose (FC-I to FC-IX), the release of the drug was found to be dependent on the relative proportions of hydroxypropylmethylcellulose and ethyl cellulose used in the tablet matrix. Mathematical treatment of the in vitro drug release data suggests that, all the formulations best fitted into first order release kinetics. Drug release from the matrix occurred by combination of two mechanisms, diffusion of drug from tablet matrix and erosion of tablet surface, which was reflected from Higuchi's model and Erosion plot. PMID:20490297

  9. Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis.

    PubMed Central

    Luiten, E J; Hop, W C; Lange, J F; Bruining, H A

    1995-01-01

    OBJECTIVE: A randomized, controlled, multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality. SUMMARY BACKGROUND DATA: Secondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis. Controlled clinical trials to study the effect of selective decontamination in such patients are not available. METHODS: Between April 22, 1990 and April 19, 1993, 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals. Patients were entered into the study if severe acute pancreatitis was indicated, on admission, by multiple laboratory criteria (Imrie score > or = 3) and/or computed tomography criteria (Balthazar grade D or E). Patients were randomly assigned to receive standard treatment (control group) or standard treatment plus selective decontamination (norfloxacin, colistin, amphotericin; selective decontamination group). All patients received full supportive treatment, and surveillance cultures were taken in both groups. RESULTS: Fifty patients were assigned to the selective decontamination group and 52 were assigned to the control group. There were 18 deaths in the control group (35%), compared with 11 deaths (22%) in the selective decontamination group (adjusted for Imrie score and Balthazar grade: p = 0.048). This difference was mainly caused by a reduction of late mortality (> 2 weeks) due to significant reduction of gram-negative pancreatic infection (p = 0.003). The average number of laparotomies per patient was reduced in patients treated with selective decontamination (p < 0.05). Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients (6%) and transient gram-negative pancreatic infection was seen in one (2%). In both groups of patients, all gram-negative aerobic pancreatic infection was preceded by

  10. Importance of Diffusion Weighted Magnetic Resonance Imaging in Evaluation of the Treatment Efficacy in Multiple Sclerosis Patients with Acute Attacks

    PubMed Central

    Sahin, Tuna; Bozgeyik, Zülküf; Menzilcioglu, Mehmet Sait; Citil, Serdal; Erbay, Mehmet Fatih

    2015-01-01

    Summary Background We planned to investigate contribution of DWMR to the treatment efficacy with ADC values which were measured in acute and chronic plaque before and after MS treatment. ADC changes in normal appearing white matter (NAWM) in patients with MS and healthy volunteers were also evaluated in this study. Material/Methods 25 patients with MS and 30 healthy subjects with normal brain MR findings were included to our study. Contrast enhancement in plaque was evaluated as an acute, and non-contrast enhancement in plaque was evaluated as a chronic. Also, ADC measurements were performed using the same parameters in NAWM in plaque neighborhood and volunteers. Results were compared with appropriate statistical methods. Results ADC values in acute and chronic plaques were decreased after the treatment, and these reductions were statistically significant for acute plaqus in b500 and for chronic plaques in b500 and b1000. The mean ADC values were measured as 1.53±0.49×10−3 and 1.43±0.58×10−3 in acute plaques and 1.40±0.35×10−3 and 1.34±0.36×10−3 mm2/sec in chronic plaques before and after the treatment. Conclusions We think that DWMR have important role due to quantitative measurement ability in the evaluation of the treatment efficacy of the MS patients with acute attack in addition to contrast-enhanced MR sequence. PMID:26740826

  11. Minocycline prevents paraquat-induced cell death through attenuating endoplasmic reticulum stress and mitochondrial dysfunction.

    PubMed

    Huang, Chuen-Lin; Lee, Yi-Chao; Yang, Ying-Chen; Kuo, Tsun-Yung; Huang, Nai-Kuei

    2012-03-25

    Paraquat (PQ) was demonstrated to induce dopaminergic neuron death and is used as a Parkinson's disease (PD) mimetic; however, its mechanism remains contradictory. Alternatively, minocycline is a second-generation tetracycline and is undergoing clinical trials for treating PD with an unresolved mechanism. We thus investigated the molecular mechanism of minocycline in preventing PQ-induced cytotoxicity. In this study, minocycline was effective in preventing PQ-induced apoptotic cell death, which involves the cleavages of poly (ADP-ribose) polymerase (PARP) and caspase 3 and increased fluorescence intensity of annexin V-FITC. In addition, PQ also quickly induced alterations of unfolded protein responses (UPRs) and subsequently dysfunction of the mitochondria (such as the decrease in membrane potential and increase in membrane permeability and superoxide formation). Finally, the mechanism of minocycline in preventing PQ-induced apoptosis might be mediated by attenuating endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which respectively results in caspase-12 activation and the release of H2O2, HtrA2/Omi, and Smac/Diablo. Thus, minocycline could possibly be used to treat other neurodegenerative disorders with similar pathologic mechanisms. PMID:22245251

  12. Comparison of doxycycline and minocycline in the inhibition of VEGF-induced smooth muscle cell migration

    PubMed Central

    Yao, Jianhua S.; Shen, Fanxia; Young, William L.; Yang, Guo-Yuan

    2007-01-01

    Smooth muscle migration plays an important role during angiogenesis and vascular remodeling. In this study, we examined the effects of doxycycline and minocycline on vascular endothelial growth factor (VEGF)-induced human aortic smooth muscle cell (HASMCs) migration, and explored the mechanisms in which doxycycline or minocycline inhibit HASMC migration. We demonstrated that both doxycycline and minocycline attain consistent anti-angiogenic effects in the inhibition of HASMC migration via a different signal pathway (p<0.05). This effect is through attenuating VEGF-induced matrix metalloproteinase-9 (MMP-9) activity (p<0.05). Doxycycline could increase tissue inhibitors of metalloproteinases-1 (TIMP-1) expression while minocycline down-regulated PI3K/Akt phosphorylation in HASMC. Our study suggests that doxycycline has a stronger ability to inhibit MMP secretion in HASMC by up-regulating endogenous MMPs inhibitor TIMP-1, while minocycline implements anti-angiogenic effect through inhibiting HASMC migration by down-regulating PI3K/Akt pathway. PMID:17145119

  13. Minocycline Enhances the Effectiveness of Nociceptin/Orphanin FQ during Neuropathic Pain

    PubMed Central

    Popiolek-Barczyk, Katarzyna; Rojewska, Ewelina; Jurga, Agnieszka M.; Makuch, Wioletta; Zador, Ferenz; Piotrowska, Anna; Przewlocka, Barbara

    2014-01-01

    Nociceptin/orphanin FQ (N/OFQ) antinociception, which is mediated selectively by the N/OFQ peptide receptor (NOP), was demonstrated in pain models. In this study, we determine the role of activated microglia on the analgesic effects of N/OFQ in a rat model of neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve. Repeated 7-day administration of minocycline (30 mg/kg i.p.), a drug that affects microglial activation, significantly reduced pain in CCI-exposed rats and it potentiates the analgesic effects of administered N/OFQ (2.5–5 μg i.t.). Minocycline also downregulates the nerve injury-induced upregulation of NOP protein in the dorsal lumbar spinal cord. Our in vitro study showed that minocycline reduced NOP mRNA, but not protein, level in rat primary microglial cell cultures. In [35S]GTPγS binding assays we have shown that minocycline increases the spinal N/OFQ-stimulated NOP signaling. We suggest that the modulation of the N/OFQ system by minocycline is due to the potentiation of its neuronal antinociceptive activity and weakening of the microglial cell activation. This effect is beneficial for pain relief, and these results suggest new targets for the development of drugs that are effective against neuropathic pain. PMID:25276817

  14. Acute myocardial infarction following erlotinib treatment for NSCLC: A case report

    PubMed Central

    DING, SHANSHAN; LONG, FEI; JIANG, SHUJUAN

    2016-01-01

    Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, is an oral targeted anticancer drug that is used to treat non-small cell lung cancer (NSCLC). Previous studies have confirmed that erlotinib is safe and is well-tolerated by patients. The most common adverse reactions observed following erlotinib treatment include a rash and mild diarrhea. In the current study, the first case of acute myocardial infarction following one month of treatment with erlotinib in a 63-year-old male NSCLC patient is presented. The present study highlights the importance of clinicians remaining cautious following erlotinib administration. In elderly NSCLC patients and those with a history of coronary heart disease, cardiac function must be carefully monitored following erlotinib treatment so that serious adverse reactions, such as myocardial infarction, may be identified early and treated quickly. PMID:27313772

  15. History, Evolution, and Importance of Emergency Endovascular Treatment of Acute Ischemic Stroke.

    PubMed

    Holodinsky, Jessalyn K; Yu, Amy Y X; Assis, Zarina A; Al Sultan, Abdulaziz S; Menon, Bijoy K; Demchuk, Andrew M; Goyal, Mayank; Hill, Michael D

    2016-05-01

    More than 800,000 people in North America suffer a stroke each year, with ischemic stroke making up the majority of these cases. The outcomes of ischemic stroke range from complete functional and cognitive recovery to severe disability and death; outcome is strongly associated with timely reperfusion treatment. Historically, ischemic stroke has been treated with intravenous thrombolytic agents with moderate success. However, five recently published positive trials have established the efficacy of endovascular treatment in acute ischemic stroke. In this review, we will discuss the history of stroke treatments moving from various intravenous thrombolytic drugs to intra-arterial thrombolysis, early mechanical thrombectomy devices, and finally modern endovascular devices. Early endovascular therapy failures, recent successes, and implications for current ischemic stroke management and future research directions are discussed. PMID:27021771

  16. [CT-guided percutaneous drainage in the treatment of acute necrotizing pancreatitis].

    PubMed

    Szentkereszty, Z; Kerekes, L; Hallay, J; Péter, M; Sápy, P

    2001-02-01

    The authors analysed the results of the treatment of 24 patients with acute necrotizing pancreatitis. Besides intensive and operative treatment prophylactic antibiotics, early naso-jejunal feeding, CT guided percutaneous peripancreatic drainage are favourable to avoid septic complications and to postpone the first operation. In 11 patients percutaneous drainage was performed. Using percutaneous drainage three patients (33.3%) recovered without operation, the mean drainage time was 23.4 days. The first operation could be postponed in the other 8 patients after percutaneous drainage. No complications occurred as result of the interventions, although in one patient the drain slipped out spontaneously. Due to the complex treatment the total mortality rate was 12.5%. PMID:11299857

  17. Acupuncture as a primary and independent treatment in the acute phases of sudden sensorineural hearing loss

    PubMed Central

    Jin, Yuanyuan; Lu, Ming

    2016-01-01

    Abstract Sudden sensorineural hearing loss (SSHL) is an otological emergency defined as a rapid hearing loss, seriously affects patient's social life. To data, no study has reported the treatment by acupuncture alone in the acute phase. In this report, Acupuncture and Moxibustion therapy of excitation-focus transfer is outlined. The patient was a 26-year-old young woman who had an SSHL coupled with ear fullness. The patient had no past medical history, but she had undergone variable emotions and had a history of excessive noise exposure. The patient refused to receive any medicine especially steroids and hyperbaric oxygen therapy. She just only received acupuncture treatment. Her symptoms and outcome measurements were improved every week and completely recovered after the last week. Even though the article presents a single case and is based on self-reports, there are very clear trends on how patients with SSHL responded to acupuncture treatments. PMID:27368045

  18. Paliperidone Palmitate Once-Monthly Injectable Treatment for Acute Exacerbations of Schizoaffective Disorder.

    PubMed

    Fu, Dong-Jing; Turkoz, Ibrahim; Simonson, R Bruce; Walling, David; Schooler, Nina; Lindenmayer, Jean-Pierre; Canuso, Carla; Alphs, Larry

    2016-08-01

    The optimal treatment for schizoaffective disorder (SCA) is not well established. In this initial 6-month open-label treatment period of a large, multiphase, relapse-prevention study, the efficacy and safety of paliperidone palmitate once-monthly (PP1M) injectable were evaluated in subjects with symptomatic SCA. Subjects with acute exacerbation of SCA (ie, with psychotic and either depressive and/or manic symptoms) were enrolled and treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers (combination therapy group). After flexible-dose treatment with PP1M for 13 weeks, stabilized subjects continued into a 12-week fixed-dose PP1M treatment period. A total of 667 subjects were enrolled; 320 received monotherapy and 347 received PP1M as combination therapy; 334 subjects completed the entire 25-week treatment. Statistically significant and clinically meaningful improvements from baseline were observed for all efficacy measures in psychosis (per Positive and Negative Syndrome Scale), mood symptoms (per Young Mania Rating Scale and Hamilton Depression Rating Scale-21 items), and functioning (per Personal and Social Performance Scale) from week 1 to all time points during the 25-week treatment period (P < 0.001). Similar improvements in efficacy measures were observed between subjects receiving monotherapy or combination therapy. Efficacy benefits persisted throughout the 25-week period. The most common adverse events were akathisia (11.1%), injection-site pain (10.6%), and insomnia (10.0%). Paliperidone palmitate once-monthly administered as monotherapy or in combination with mood stabilizers or antidepressants in patients with an acute exacerbation of SCA provided rapid, broad, and persistent reduction in psychotic, depressive, and manic symptoms, as well as improved functioning. PMID:27322760

  19. Clinical analysis of cause, treatment and prognosis in acute kidney injury patients.

    PubMed

    Yang, Fan; Zhang, Li; Wu, Hao; Zou, Hongbin; Du, Yujun

    2014-01-01

    Acute kidney injury (AKI) is characterized by an abrupt decline in renal function, resulting in an inability to secrete waste products and maintain electrolyte and water balance, and is associated with high risks of morbidity and mortality. This study retrospectively analyzed clinical data, treatment, and prognosis of 271 hospitalized patients (172 males and 99 females) diagnosed with AKI from December, 2008 to December, 2011. In addition, this study explored the association between the cause of AKI and prognosis, severity and treatment of AKI. The severity of AKI was classified according to the Acute Kidney Injury Network (AKIN) criteria. Renal recovery was defined as a decrease in a serum creatinine level to the normal value. Prerenal, renal, and postrenal causes accounted for 36.5% (99 patients), 46.5% (126 patients) and 17.0% (46 patients), respectively, of the incidence of AKI. Conservative, surgical, and renal replacement treatments were given to 180 (66.4%), 30 (11.1%) and 61 patients (22.5%), respectively. The overall recovery rate was 21.0%, and the mortality rate was 19.6%. Levels of Cl(-), Na(+) and carbon dioxide combining power decreased with increasing severity of AKI. Cause and treatment were significantly associated with AKI prognosis. Likewise, the severity of AKI was significantly associated with cause, treatment and prognosis. Multivariate logistic regression analysis found that respiratory injury and multiple organ dysfunction syndrome (MODS) were associated with AKI patient death. Cause, treatment and AKIN stage are associated with the prognosis of AKI. Respiratory injury and MODS are prognostic factors for death of AKI patients. PMID:24586237

  20. Efficacy and tolerability of almotriptan versus zolmitriptan for the acute treatment of menstrual migraine.

    PubMed

    Allais, G; Acuto, G; Cabarrocas, X; Esbri, R; Benedetto, C; Bussone, G

    2006-05-01

    Menstrual migraine (MM) attacks are a challenge for the headache specialist, because they are particularly difficult to treat. Almotriptan is a second-generation triptan successfully used for the acute treatment of migraine. No data on the efficacy and safety of almotriptan in MM treatment have been published previously. The objective was to evaluate the efficacy and tolerability of almotriptan in the symptomatic treatment of MM attacks and to compare these parameters to those obtained with zolmitriptan, another second-generation triptan. Data from a multicentre, multinational, randomised, double-blind, parallel clinical trial, conducted at 118 centres in 9 European countries, to evaluate the efficacy and tolerability of almotriptan 12.5 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine were analysed retrospectively. Of the 1061 patients included, 902 were women and 255 of these treated a MM attack: 136 with almotriptan and 119 with zolmitriptan. No significant difference between the two treatments was found. Two hours after dosing, 67.9% of almotriptan-treated and 68.6% of zolmitriptan-treated patients had obtained pain relief; while 44.9% and 41.2%, respectively, were pain free. Recurrence rates 2-24 h after dosing were 32.8% for almotriptan and 34.7% for zolmitriptan. Adverse events in the 24 h after dosing were reported by 19.8% of those taking almotriptan and 23.1% of those taking zolmitriptan. In conclusion, almotriptan is effective and safe in the treatment of MM attacks. PMID:16688629

  1. Paliperidone Palmitate Once-Monthly Injectable Treatment for Acute Exacerbations of Schizoaffective Disorder

    PubMed Central

    Fu, Dong-Jing; Turkoz, Ibrahim; Simonson, R. Bruce; Walling, David; Schooler, Nina; Lindenmayer, Jean-Pierre; Canuso, Carla; Alphs, Larry

    2016-01-01

    Abstract The optimal treatment for schizoaffective disorder (SCA) is not well established. In this initial 6-month open-label treatment period of a large, multiphase, relapse-prevention study, the efficacy and safety of paliperidone palmitate once-monthly (PP1M) injectable were evaluated in subjects with symptomatic SCA. Subjects with acute exacerbation of SCA (ie, with psychotic and either depressive and/or manic symptoms) were enrolled and treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers (combination therapy group). After flexible-dose treatment with PP1M for 13 weeks, stabilized subjects continued into a 12-week fixed-dose PP1M treatment period. A total of 667 subjects were enrolled; 320 received monotherapy and 347 received PP1M as combination therapy; 334 subjects completed the entire 25-week treatment. Statistically significant and clinically meaningful improvements from baseline were observed for all efficacy measures in psychosis (per Positive and Negative Syndrome Scale), mood symptoms (per Young Mania Rating Scale and Hamilton Depression Rating Scale—21 items), and functioning (per Personal and Social Performance Scale) from week 1 to all time points during the 25-week treatment period (P < 0.001). Similar improvements in efficacy measures were observed between subjects receiving monotherapy or combination therapy. Efficacy benefits persisted throughout the 25-week period. The most common adverse events were akathisia (11.1%), injection-site pain (10.6%), and insomnia (10.0%). Paliperidone palmitate once-monthly administered as monotherapy or in combination with mood stabilizers or antidepressants in patients with an acute exacerbation of SCA provided rapid, broad, and persistent reduction in psychotic, depressive, and manic symptoms, as well as improved functioning. PMID:27322760

  2. Eosinophilic Fasciitis and Acute Encephalopathy Toxicity from Pembrolizumab Treatment of a Patient with Metastatic Melanoma.

    PubMed

    Khoja, Leila; Maurice, Catherine; Chappell, MaryAnne; MacMillan, Leslie; Al-Habeeb, Ayman S; Al-Faraidy, Nada; Butler, Marcus O; Rogalla, Patrik; Mason, Warren; Joshua, Anthony M; Hogg, David

    2016-03-01

    Anti-PD-1 inhibitors have significant activity in metastatic melanoma. Responses often occur early and may be sustained. The optimal duration of treatment with these agents is unknown. Here, we report the case of a 51-year-old woman treated with pembrolizumab, as part of the Keynote-001 trial, as first-line treatment for metastatic disease. She experienced a complete response after 13.8 months of treatment with no adverse events. One month after the last drug infusion and 18 months from starting treatment, the patient presented with eosinophilic fasciitis. She then developed acute confusion and weakness, thought to be due to intracranial vasculitis. High-dose steroids were initiated with resolution of the fasciitis. Aspirin was commenced for presumed vasculitis with resolution of the neurologic symptoms. To our knowledge, there are no previous reports of eosinophilic fasciitis or cerebral vasculitis due to anti-PD-1 agents. This case demonstrates that toxicity may occur in association with pembrolizumab treatment after a prolonged period of treatment without toxicity. Future trials should explore the optimal duration of treatment with pembrolizumab. PMID:26822024

  3. Treatment of patients with mild acute ischemic stroke and associated large vessel occlusion.

    PubMed

    Cerejo, Russell; Cheng-Ching, Esteban; Hui, Ferdinand; Hussain, M Shazam; Uchino, Ken; Bullen, Jennifer; Toth, Gabor

    2016-08-01

    Several recent studies have shown that patients presenting with mild acute ischemic stroke (mAIS) symptoms may have an unfavorable natural history. The presence of associated large vessel occlusion (LVO) may lead to even worse outcomes, but most mAIS patients are still excluded from acute stroke treatment (AST). A retrospective review of patients with acute ischemic stroke presenting to our institution between 2010 and 2014 was carried out. Inclusion criteria were mAIS (initial National Institutes of Health Stroke Scale [NIHSS] ⩽7) due to LVO, presenting within 6hours from onset. Demographics, treatments and short-term outcomes were analyzed. Favorable 30day outcome was defined as modified Rankin Scale (mRS) ⩽2. Out of 2636 patients, 62 patients (median age 63years, 33 (53.2%) males) met inclusion criteria. The anterior circulation was involved in 74.1%. Median admission NIHSS and pre-admission mRS were 4 and 0, respectively. Twenty-three patients (71.8%) received AST (intravenous tissue plasminogen activator: 14, intra-arterial therapy: 4, both: 5). Favorable outcomes were 4.5 times higher in treated (78.3%) versus untreated (53.8%) patients (odds ratio 4.5, 95% confidence interval 1.26-19.2; p=0.028). None of the treated patients had symptomatic intracranial hemorrhage. We demonstrate that a significant proportion of untreated mAIS patients with LVO have an unfavorable natural history. Our results suggest better outcomes in patients who receive early therapy rather than conservative management. The detection of LVO, even with mild clinical symptoms, may prompt rapid treatment considerations. PMID:27050916

  4. Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

    PubMed

    Denier, Niklaus; Schmidt, André; Gerber, Hana; Vogel, Marc; Huber, Christian G; Lang, Undine E; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan

    2015-12-01

    Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction. PMID:26441146

  5. Acute phase treatment of venous thromboembolism: advanced therapy. Systemic fibrinolysis and pharmacomechanical therapy.

    PubMed

    Konstantinides, Stavros V; Wärntges, Simone

    2015-06-01

    Venous thromboembolism, which encompasses deep-vein thrombosis and acute pulmonary embolism (PE), represents a major contributor to global disease burden worldwide. For patients who present with cardiogenic shock or persistent hypotension (acute high-risk PE), there is consensus that immediate reperfusion treatment applying systemic fibrinolysis or, in the case of a high bleeding risk, surgical or catheter-directed techniques, is indicated. On the other hand, for the large, heterogeneous group of patients presenting without overt haemodynamic instability, the indications for advanced therapy are less clear. The recently updated guidelines of the European Society of Cardiology emphasise the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for distinguishing between an intermediate and a low risk for an adverse early outcome. In intermediate-high-risk PE defined by the presence of both right ventricular dysfunction on echocardiography (or computed tomography) and a positive troponin (or natriuretic peptide) test, the bleeding risks of full-dose fibrinolytic treatment have been shown to outweigh its potential clinical benefits unless clinical signs of haemodynamic decompensation appear (rescue fibrinolysis). Recently published trials suggest that catheter-directed, ultrasound-assisted, low-dose local fibrinolysis may provide an effective and particularly safe treatment option for some of these patients. PMID:25789580

  6. [Bronchial asthma and chronic obstructive pulmonary disease with acute exacerbation: preclinical differential diagnostic and emergency treatment].

    PubMed

    Friege, B; Friege, L; Pelz, J; Weber, M; von Spiegel, T; Schröder, S

    2009-06-01

    Chronic obstructive pulmonary disease (COPD) and bronchial asthma are the most common causes of obstructive pulmonary diseases and acute dyspnoea. In the preclinical emergency situation a distinction between bronchial asthma and exacerbated COPD is difficult because symptoms are similar. Although the preclinical measures differ only marginally, a differential diagnosis from other causes of respiratory obstruction and acute dyspnoea, such as cardiac decompensation, anaphylaxis, aspiration of foreign bodies, tension pneumothorax and inhalation trauma is necessary because alternative treatment options are required. In the treatment of COPD and bronchial asthma inhalative bronchodilatory beta(2)-mimetics are the first choice especially for serious obstructive emergencies because there is an unfavorable relationship between effect and side-effects for the intravenous route. Dosable aerosols, nebulization and if necessary, continuous nebulization, are appropriate application forms even for serious obstructive crises with the need of a respirator. In these cases a minimal inspiratory flow in patients is not required. Theophylline only plays a minor role to beta(2)-mimetics and anticholinergics as a bronchodilator in asthma and COPD guidelines, even in serious obstructive diseases. For severe asthma attacks the administration of magnesium is a possible additional option. Systemic intravenous administration of steroids has an anti-inflammatory effect and for this reason is the second column of treatment for both diseases. Invasive ventilation remains a last resort to ensure respiratory function and indications for this are given in patients with clinical signs of impending exhaustion of breathing. PMID:19424670

  7. Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia.

    PubMed Central

    Moëll, C; Garwicz, S; Westgren, U; Wiebe, T; Albertsson-Wikland, K

    1989-01-01

    The spontaneous secretion of growth hormone during a 24 hour period and the response of growth hormone to growth hormone releasing hormone was studied in 13 girls who had received treatment for acute lymphoblastic leukemia that included cranial irradiation with 20-24 Gy in 12-14 fractions. At the time of investigation the girls were at varying stages of puberty and had normal concentrations of thyroid hormones. The mean interval between the end of treatment and investigation was 4.6 years. The mean age at onset of the disease was 3.2 years and at investigation 10.7 years. The average attained height equalled -0.3 SD at onset, and -1.0 SD at the time of investigation. Secretion of growth hormone was substantially reduced compared with controls and did not increase during puberty. A prompt rise in growth hormone secretion was seen after injection of growth hormone releasing hormone, but the mean maximum growth hormone concentration was, however, only 25 mU/l. There was no correlation between the 24 hour secretion and growth hormone response to growth hormone releasing hormone, or the time since irradiation. These results confirm earlier work that suggested that girls who had received treatment for acute lymphoblastic leukaemia, that included cranial irradiation, have a comparative growth hormone insufficiency characterised by normal prepubertal growth and slow growth during puberty because of an inability to respond to the increased demands for growth hormone at that time. PMID:2494952

  8. Pharmacokinetics and interactions of headache medications, part I: introduction, pharmacokinetics, metabolism and acute treatments.

    PubMed

    Sternieri, Emilio; Coccia, Ciro Pio Rosario; Pinetti, Diego; Ferrari, Anna

    2006-12-01

    Recent progress in the treatment of primary headaches has made available specific, effective and safe medications for these disorders, which are widely spread among the general population. One of the negative consequences of this undoubtedly positive progress is the risk of drug-drug interactions. This review is the first in a two-part series on pharmacokinetic drug-drug interactions of headache medications. Part I addresses acute treatments. Part II focuses on prophylactic treatments. The overall aim of this series is to increase the awareness of physicians, either primary care providers or specialists, regarding this topic. Pharmacokinetic drug-drug interactions of major severity involving acute medications are a minority among those reported in literature. The main drug combinations to avoid are: i) NSAIDs plus drugs with a narrow therapeutic range (i.e., digoxin, methotrexate, etc.); ii) sumatriptan, rizatriptan or zolmitriptan plus monoamine oxidase inhibitors; iii) substrates and inhibitors of CYP2D6 (i.e., chlorpromazine, metoclopramide, etc.) and -3A4 (i.e., ergot derivatives, eletriptan, etc.), as well as other substrates or inhibitors of the same CYP isoenzymes. The risk of having clinically significant pharmacokinetic drug-drug interactions seems to be limited in patients with low frequency headaches, but could be higher in chronic headache sufferers with medication overuse. PMID:17125411

  9. Minimising time to treatment: targeted strategies to minimise time to thrombolysis for acute ischaemic stroke.

    PubMed

    Tai, Y J; Yan, B

    2013-11-01

    Time to thrombolysis is a critical determinant of favourable outcomes in acute ischaemic stroke. It is not infrequent that patient outcomes are compromised due to out-of-hospital and in-hospital time delays. On the other hand, time delays could be minimised through the identification of barriers and the implementation of targeted solutions. This review outlines the different strategies in minimising treatment delays and offers recommendations. Literature search in PubMed, Medline and EBSCO Host was conducted to identify studies that are relevant to reduction of time to treatment from January 1995 to December 2012. Strategies to reduce time to thrombolysis are categorised into pre-hospital strategies, in-hospital strategies and post-treatment decision strategies. Proposed pre-hospital strategies include public education on stroke symptoms awareness, prioritising stroke by emergency medical services, increasing ease of access to medical records, pre-hospital notification, and mobile computed tomography scanning. In-hospital strategies include a streamlined code stroke system, computed tomography scanner co-location with emergency department, 24/7 availability of stroke physicians, point-of-care laboratory testing and access to expert neuroimaging interpretation. Post-decision strategies include increasing availability of intravenous thrombolysis and simplification of informed consent procurement. Time to thrombolysis delays is multifactorial. Effective reduction of time delays for acute ischaemic stroke requires the correct identification of and targeted strategies to overcome time barriers. PMID:23734983

  10. Xyloglucan for the Treatment of Acute Gastroenteritis in Children: Results of a Randomized, Controlled, Clinical Trial

    PubMed Central

    Pleșea Condratovici, Cătălin; Bacarea, Vladimir; Piqué, Núria

    2016-01-01

    Background. Xyloglucan, a film-forming agent, improves intestinal mucosa resistance to pathologic damage. The efficacy, safety, and time of onset of the antidiarrheal effect of xyloglucan were assessed in children with acute gastroenteritis receiving oral rehydration solution (ORS). Methods. This randomized, controlled, open-label, parallel-group, multicenter, clinical trial included children (3 months–12 years) with acute gastroenteritis of infectious origin. Children were randomized to xyloglucan and ORS, or ORS only, for 5 days. Diarrheal symptoms, including stool number/characteristics, and safety were assessed at baseline and after 2 and 5 days and by fulfillment of a parent diary card. Results. Thirty-six patients (58.33% girls) were included (n = 18/group). Patients receiving xyloglucan and ORS had better symptom evolution than ORS-only recipients, with a faster onset of action. At 6 hours, xyloglucan produced a significantly greater decrease in the number of type 7 stools (0.11 versus 0.44; P = 0.027). At days 3 and 5, xyloglucan also produced a significantly greater reduction in types 6 and 7 stools compared with ORS alone. Xyloglucan plus ORS was safe and well tolerated. Conclusions. Xyloglucan is an efficacious and safe option for the treatment of acute gastroenteritis in children, with a rapid onset of action in reducing diarrheal symptoms. This study is registered with ISRCTN number 65893282. PMID:27212943

  11. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

    PubMed Central

    Eriksson, A; Österroos, A; Hassan, S; Gullbo, J; Rickardson, L; Jarvius, M; Nygren, P; Fryknäs, M; Höglund, M; Larsson, R

    2015-01-01

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis. PMID:25885427

  12. Platelet-rich plasma (PRP) treatment of sports-related severe acute hamstring injuries

    PubMed Central

    Guillodo, Yannick; Madouas, Gwénaelle; Simon, Thomas; Le Dauphin, Hermine; Saraux, Alain

    2015-01-01

    Summary Purpose hamstring injury is the most common musculoskeletal disorder and one of the main causes of missed sporting events. Shortening the time to return to play (TTRTP) is a priority for athletes and sports medicine practitioners. Hypothesis platelet-rich plasma (PRP) injection at the site of severe acute hamstring injury increases the healing rate and shortens the TTRTP. Study design Cohort study. Methods all patients with ultrasonography and MRI evidence of severe acute hamstring injury between January 2012 and March 2014 were offered PRP treatment. Those who accepted received a single intramuscular PRP injection within 8 days post-injury; the other patients served as controls. The same standardized rehabilitation program was used in both groups. A physical examination and ultrasonography were performed 10 and 30 days post-injury, then a phone interview 120 days post-injury, to determine the TTRTP at the pre-injury level. Results of 34 patients, 15 received PRP and 19 did not. Mean TTRTP at the pre-injury level was 50.9±10.7 days in the PRP group and 52.8±15.7 days in the control group. The difference was not statistically significant. Conclusion a single intramuscular PRP injection did not shorten the TTRTP in sports people with severe acute hamstring injuries. PMID:26958537

  13. [Acute rheumatic fever and infectious-inflammatory diseases of the pharynx: the relationship, treatment, and prophylaxis].

    PubMed

    Belov, B S

    2015-01-01

    The relationship between pharyngeal infections, such as tonsillitis and pharyngitis, caused by group A beta-hemolytic streptococci (BHSA) and acute rheumatic fever (ARF) is a well-established fact confirmed by numerous studies carried out along the following lines: epidemiological, immunological, therapeutic, and prophylactic. The currently available data provide an opportunity to discuss the existence of «rheumatogenic» BHSA strains exhibiting a number of characteristic clinical and morphological properties. According to the current recommendations penicillins remain the means of first-line therapy for the treatment of acute forms of BHSA-induced tonsillitis and pharyngitis, whereas the macrolides should be applied only as the alternative medications in the patients with intolerance to beta-lactam antibiotics. This article contains characteristics of BHSA-carrier state and the principal indications for the prescription of antibiotics to the patients with these conditions. The key principle of secondary medicamental prophylaxis of acute respiratory infections are expounded along with the main fines of future research on the problems associated with BHSA-induced pharyngeal infections. PMID:26870861

  14. Treatment-related deaths in second complete remission in childhood acute myeloid leukaemia.

    PubMed

    Molgaard-Hansen, Lene; Möttönen, Merja; Glosli, Heidi; Jónmundsson, Guðmundur K; Abrahamsson, Jonas; Hasle, Henrik

    2011-03-01

    The frequency and causes of treatment-related deaths (TRD) in second complete remission (CR2) in acute myeloid leukaemia (AML) were investigated in a historical, prospective cohort study of 429 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-88 and -93 trials. Relapse occurred in 158 children (39%). Seventeen (18%) of the 96 patients entering CR2 suffered TRD. The main causes were infection (59%) and complications from graft-versus-host disease (22%). Fourteen (82%) of 17 TRDs occurred in children undergoing haematopoietic stem cell transplantations (HSCT). Optimal supportive care after HSCT is essential, and studies on risk factors for TRD are needed. PMID:21241281

  15. [Acute myeloblastic leukemia and adenocarcinoma of the rectum as secondary malignancies after treatment of rhabdomyosarcoma].

    PubMed

    Hasanbegović, E; Sabanović, S; Sporisević, L

    2000-01-01

    It is shown very rare case of eight years old girl with two secondary sicknesses: myeloic leucosis and adenocarcinoma of rectum that developed after six years of successful treatment. The diagnose of embryonal Rhabdomyosarcoma was set up in Sarajevo six years ago after surgical extirpation of tumor from orbitae and its pathohistology finding. Complete chemo and radiotherapy was performed in Germany (Bonn) according protocol (CWS 91). Diagnoses of acute myeloic leucosis and adenocarcinoma of rectum was set up according: clinical picture, peripheral blood smear, bone marrow smear and biopsy of bleeding polyp of rectum. PMID:10934835

  16. The role of Clofarabine in the treatment of adults with acute myeloid leukemia.

    PubMed

    Fozza, Claudio

    2015-03-01

    The therapeutic scenario available for adult patients with acute myeloid leukemia (AML) has shown only partial progresses over the last few years. This is especially true for refractory and relapsed AML whose outcome is still extremely disappointing. In this context Clofarabine has offered new promising perspectives within first and second line protocols. This review will firstly describe the initial development in monotherapy, considering then the different potential combination strategies which include both polichemotherapeutic regimens and less conventional approaches with new generation drugs. The potential use of Clofarabine as induction treatment for patients candidate to stem cell transplantation and within conditioning regimens will be finally evaluated. PMID:25457773

  17. Cardiac Failure 30 Years after Treatment Containing Anthracycline for Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Goldberg, John M.; Scully, Rebecca E.; Sallan, Stephen E.; Lipshultz, Steven E.

    2012-01-01

    In 1977, a 5-year-old girl diagnosed with acute lymphoblastic leukemia (ALL) was treated on DFCI Childhood ALL Protocol 77-01, receiving a cumulative doxorubicin dose of 465 mg/m2, cranial radiation, and other drugs. After being in continuous complete remission for 34 months, she developed heart failure (HF) and was treated with digoxin and furosemide. At 16, she was diagnosed and treated for dilated cardiomyopathy. Over the years she continued to have bouts of HF, which became less responsive to treatment. At 36, she received a heart transplant. Six months later, she stopped taking her medications and suffered a sudden cardiac death. PMID:22584777

  18. Advances in the diagnosis and treatment of acute and chronic leukemia in Mexico.

    PubMed

    Ruiz-Argüelles, Guillermo José

    2016-04-01

    In the last 60 years, there have been substantial advances regarding the diagnosis and treatment of patients with acute and chronic leukemia in Mexico. Immunologic and molecular classifications of these diseases have improved both diagnosis and therapeutic capabilities. Although the pace of diagnostic and therapeutic advances has been slower compared with developed countries, Mexico is at the forefront among developing countries. Supporting research in these fields is expected to enhance the generation of new knowledge and improve the care of patients suffering from these diseases. PMID:27557388

  19. Effect of acute fentanyl treatment on synaptic plasticity in the hippocampal CA1 region in rats

    PubMed Central

    Tian, Hai; Xu, Yueming; Liu, Fucun; Wang, Guowei; Hu, Sanjue

    2015-01-01

    Postoperative cognitive dysfunction (POCD), mainly characterized by short-term decline of learning and memory, occurs after operations under anesthesia. However, the underlying mechanisms are poorly understood. The μ-opioid receptors (MOR) are highly expressed in interneurons of hippocampus, and is believed to be critical for the dysfunction of synaptic plasticity between hippocampal neurons. Therefore, we investigated the effect of fentanyl, a strong agonist of MOR and often used for anesthesia and analgesia in clinical settings, on hippocampal synaptic plasticity in the Schaffer-collateral CA1 pathway during acute exposure and washout in vitro. Our results revealed that acute fentanyl exposure (0.01, 0.1, 1 μM) dose-dependently increased the field excitatory postsynaptic potentials (fEPSPs), which was prevented by pre-administration of picrotoxin (50 μM) or MOR antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH2 (CTOP, 10 μM). While fentanyl exposure-increased fEPSPs amplitude was prevented by picrotoxin [an inhibitor of γ-aminobutyric acid receptor (GABAR)] treatment or fentanyl washout, pretreatment of picrotoxin failed to prevent the fentanyl-impaired long-term potentiation (LTP) of synaptic strength as well as the fentanyl-enhanced long-term depression (LTD). These results demonstrated that fentanyl acute exposure and washout increases hippocampal excitability in the Schaffer-collateral CA1 pathway, depending on disinhibiting interneurons after MOR activation. In addition, fentanyl acute exposure and washout modulated synaptic plasticity, but the inhibitory activation was not critical. Elucidating the detailed mechanisms for synaptic dysfunction after fentanyl exposure and washout may provide insights into POCD generation after fentanyl anesthesia. PMID:26578961

  20. Analysis of Recurrence Management in Patients Who Underwent Nonsurgical Treatment for Acute Appendicitis.

    PubMed

    Liang, Tsung-Jung; Liu, Shiuh-Inn; Tsai, Chung-Yu; Kang, Chi-Hsiang; Huang, Wei-Chun; Chang, Hong-Tai; Chen, I-Shu

    2016-03-01

    The recurrence rate for acute appendicitis treated nonoperatively varies between studies. Few studies have adequately evaluated the management of these patients when appendicitis recurs. We aimed to explore the recurrence rate and management of patients with acute appendicitis that were first treated nonoperatively.We identified patients in the Taiwan National Health Insurance Research Database who were hospitalized due to acute appendicitis for the first time between 2000 and 2010 and received nonsurgical treatment. The recurrence and its management were recorded. Data were analyzed to access the risk factors for recurrence and factors that influenced the management of recurrent appendicitis.Among the 239,821 patients hospitalized with acute appendicitis for the first time, 12,235 (5.1%) patients were managed nonoperatively. Of these, 864 (7.1%) had a recurrence during a median follow-up of 6.5 years. Appendectomy was performed by an open and laparoscopic approach in 483 (55.9%) and 258 (29.9%) patients, respectively. The remaining 123 (14.2%) patients were again treated nonsurgically. Recurrence was independently associated with young age, male sex, percutaneous abscess drainage, and medical center admission by multivariable analysis. In addition, age <18, a (CCI) <2, medical center admission, and a longer time to recurrence were correlated with using laparoscopy to treat recurrence. Neither type of appendicitis, percutaneous abscess drainage, nor length of first time hospital stay had an influence on the selection of surgical approach.In conclusion, a laparoscopic appendectomy can be performed in recurrent appendicitis cases, and its application may not be related to previous appendicitis severity. PMID:27015200

  1. Systematic review of probiotics for the treatment of community-acquired acute diarrhea in children

    PubMed Central

    2013-01-01

    Background Oral rehydration salts (ORS), zinc, and continued feeding are the recommended treatments for community-acquired acute diarrhea among young children. However, probiotics are becoming increasingly popular treatments for diarrhea in some countries. We sought to estimate the effect of probiotics on diarrhea morbidity and mortality in children < 5 years of age. Methods We conducted a systematic review of randomized controlled trials to estimate the effect of probiotic microorganisms for the treatment of community-acquired acute diarrhea in children. Data were abstracted into a standardized table and study quality was assessed using the Child Health Epidemiology Reference Group (CHERG) adaption of the GRADE technique. We measured the relative effect of probiotic treatment in addition to recommended rehydration on hospitalizations, duration and severity. We then calculated the average percent difference for all continuous outcomes and performed a meta-analysis for discrete outcomes. Results We identified 8 studies for inclusion in the final database. No studies reported diarrhea mortality and overall the evidence was low to moderate quality. Probiotics reduced diarrhea duration by 14.0% (95% CI: 3.8-24.2%) and stool frequency on the second day of treatment by 13.1% (95% CI: 0.8 – 25.3%). There was no effect on the risk of diarrhea hospitalizations. Conclusion Probiotics may be efficacious in reducing diarrhea duration and stool frequency during a diarrhea episode. However, only few studies have been conducted in low-income countries and none used zinc (the current recommendation) thus additional research is needed to understand the effect of probiotics as adjunct therapy for diarrhea among children in developing countries. PMID:24564646

  2. Effect of Tamoxifen and Lithium on Treatment of Acute Mania Symptoms in Children and Adolescents

    PubMed Central

    Fallah, Elham; Arman, Sorror; Najafi, Mostafa; Shayegh, Bahar

    2016-01-01

    Objective Many studies have supported the role of protein kinase C (PKC) inhibitors in the physiopathology and treatment of bipolar disorder in adults. Tamoxifen is one of the drugs with the effect of PKC inhibition. This study aimed to determine the effect of tamoxifen on the rate of improvement mania symptoms in the sample of children and adolescents with acute mania. Materials & Methods In this randomized, placebo-controlled clinical trial study, registered in www.irct.ir with the code of IRCT201410126418N3, overall 44 patients with bipolar disorder with acute manic episode were randomly assigned into treatment and control groups. The serum levels of lithium and tamoxifen among the participants in the treatment groups were 0.8 -1.1 mg and 20-40 mg per day respectively. Serum level of lithium among participants in the control group was similar. The main comparisons were made based on the Young Mania Rating Scale (YMRS) and Children Depression Inventory (CDI) scores of the participants at baseline and at the end of each study week. The pharmacological side effects of serum level of lithium were examined weekly. Analysis of Covariance(ANCOVA) test was used for the statistical analysis. Results There was no difference in the baseline score of YMRS and CDI in the treatment and control groups while a statistical significant difference (P < 0.05) in these scores was found between and within the groups. Conclusion The addition of tamoxifen to lithium causes a significant difference in reducing the symptoms of mania and depression in the treatment group compared to the control group. PMID:27247580

  3. Herbal drug BNO 1016 is safe and effective in the treatment of acute viral rhinosinusitis

    PubMed Central

    Jund, Rainer; Mondigler, Martin; Stammer, Holger; Stierna, Pontus; Bachert, Claus

    2015-01-01

    Abstract Conclusion: Daily intake of 480 mg of BNO 1016 for 15 days is an effective treatment in acute viral rhinosinusitis. Objectives: The pooled efficacy data of two similar randomized placebo-controlled clinical trials were analyzed. Safety was evaluated on the basis of the individual trials. Methods: The efficacy analysis was based on 589 patients. Treatment was performed orally with either 3 × 160 mg BNO 1016 (n = 294) or 3 × placebo (n = 295) for 15 days. In both trials patients underwent five visits to the investigational sites. Symptoms were evaluated according to the EPOS 2012 guideline. Ultrasonography was used to confirm the diagnosis at onset of treatment and the remission of symptoms at the last visit. Efficacy was evaluated by the investigator as the mean major symptom score (MSS) at the end of treatment (visit 5, day 14). Patients reported symptoms and social/emotional consequences of rhinosinusitis using a quality of life questionnaire (SNOT-20 GAV). Results: MSS improved during the treatment period by a mean of 10.02 ± 1.61 score points to 2.47 ± 2.55 for BNO 1016 and of 9.87 ± 1.52 to 3.63 ± 3.63 for placebo. Differences between treatment groups at end of therapy (1.16 ± 3.14 score points; p < 0.0001) and patient-assessed quality of life (p = 0.0015) were statistically significant in favor of BNO 1016. PMID:25496178

  4. Potential efficacy of early treatment of acute acoustic trauma with steroids and piracetam after gunshot noise.

    PubMed

    Psillas, George; Pavlidis, Pavlos; Karvelis, Ioannis; Kekes, George; Vital, Victor; Constantinidis, John

    2008-12-01

    The purpose of this randomized study was to evaluate the early effect of the treatment of acute acoustic trauma (AAT) with steroids and piracetam in a sample of 52 young soldiers who were exposed to intense gunfire noise (G3 rifle). These patients were divided into three groups: (1) group A (20 patients) in which the treatment began within the first hour after the AAT, (2) group B (17 patients) in which the treatment started more than 1 h later and less than 16 h after the AAT and (3) group C (15 patients) in which the treatment began after 24 h or more. One month after the treatment onset, 36 (69%) patients of all the groups showed hearing improvement (complete-partial recovery) in the pure tone audiometry. The greater number of patients who showed complete recovery after AAT was noted in group A (65%) compared to group B (23.5%) and C (13.3%). Moreover, in group A, in the final audiogram, the averaged hearing threshold was statistically better (P < 0.001) than that of groups B and C. In spite of the lack of control group, our data demonstrated the possible effectiveness of the immediate onset of treatment of AAT. PMID:18463885

  5. Adjuvant therapy with minocycline for schizophrenia (The MINOS Trial): study protocol for a double-blind randomized placebo-controlled trial

    PubMed Central

    2013-01-01

    Background Schizophrenia is understood to be a heterogeneous brain condition with overlapping symptom dimensions. The negative symptom dimension, with its protean cognitive manifestations, responds poorly to treatment, which can be a particular challenge in countries where clozapine therapy is not available. Preliminary data indicate that minocycline may be beneficial adjunct in the treatment of schizophrenia: positive, negative, and cognitive symptoms. In this study we aim to assess the efficacy of adjunctive minocycline to alleviate symptoms of schizophrenia in patients who have failed to respond to a therapeutic trial of antipsychotic medications. Methods The study is a parallel group, double-blind, randomized, placebo-controlled trial. Participants will be adults (aged 18 years and above) with first episode or relapse episode of schizophrenia of under 5 years’ duration. Patients who failed to show adequate therapeutic response to at least one antipsychotic medication given for a minimum of 4 weeks will be recruited from a psychiatry hospital in Addis Ababa and a psychiatry clinic in Butajira, Ethiopia. A total of 150 participants (75 in each arm) will be required to detect a five-point mean difference between the intervention arms adjusting for baseline symptom severity, at 90% power and 95% confidence. Patients in the intervention arm will receive minocycline (200 mg/day orally) added on to the regular antipsychotic medications participants are already on. Those in the placebo arm will receive an inactive compound identical in physical appearance to minocycline. Intervention will be offered for 12 weeks. Diagnosis will be established using the operational criteria for research (OPCRIT). Primary outcome measure will be a change in symptom severity measured using the positive and the negative syndrome scale for schizophrenia (PANSS). Secondary outcome measures will include changes in severity of negative symptoms, proportion achieving remission, and level

  6. Endovascular Acute Stroke Treatment Performed by Vascular Interventional Radiologists: Is It Safe and Efficacious?

    SciTech Connect

    Fjetland, Lars Roy, Sumit; Kurz, Kathinka D.; Larsen, Jan Petter; Kurz, Martin W.

    2012-10-15

    Purpose: To evaluate the safety and efficacy of neurointerventional procedures in acute stroke patients performed by a team of vascular interventional radiologists in close cooperation with diagnostic neuroradiologists and stroke neurologists and to compare the results with those of previous reports from centres with specialised interventional neuroradiologists. Material and Methods: A total of 39 patients with acute ischemic stroke due to large-vessel occlusion not responding to or not eligible for intravenous thrombolysis were treated with either intra-arterial thrombolysis or mechanical thrombectomy (Penumbra System or solitaire FR thrombectomy system, respectively) and included in our prospective study. Outcomes were measured using the modified Rankin scale after 90 days, and recanalization was assessed by thrombolysis using the myocardial infarction score. Results: Mean patient age was 68.3 {+-} 14.2 years; the average National Institutes of Health Stroke Scale score at hospital admission was 17.2 (SD = 6.2 [n = 38]). Successful recanalization was achieved in 74.4 % of patients. Median time from clinical onset to recanalization was 5 h 11 min. Procedure-related complications occurred in 5 % of patients, and 7.5 % had a symptomatic intracerebral hemorrhage. Of the patients, 22.5 % died within the first 90 postprocedural days, 5 % of these from cerebral causes. Patients who were successfully recanalized had a clinical better outcome at follow-up than those in whom treatment failed. Of the patients, 35.9 % had an mRS score {<=}2 after 90 days. Conclusion: Our results are in line with those in the published literature and show that a treatment strategy with general interventional radiologists performing neurointerventional procedures in acute stroke patients with large vessel occlusions can be achieved to the benefit of patients.

  7. Prostaglandin synthetase inhibition with indomethacin rectal suppositories in the treatment of acute and chronic urinary calculus obstruction.

    PubMed

    Al-Waili, N S

    1986-03-01

    The effect of indomethacin suppositories on both acute urinary colic and urinary calculus, resistant or refractory to conventional therapy with analgesics and spasmolytics was investigated. Fifty-five patients with acute urinary colic refractory to treatment with repeated injections of antispasmodics and analgesics had dramatic or complete pain relief after receiving indomethacin suppositories (100 mg) (P less than 0.01). Fifteen of the 55 patients passed urinary stones within 30 days of treatment with indomethacin. Three out of 30 other patients with renal or ureteric stones were treated with indomethacin suppositories (100 mg) twice daily. Twenty-one of the 30 patients passed their stones within 30 days of treatment. It is concluded that indomethacin suppositories can relieve acute urinary colic resistant to treatment with analgesic/antispasmodic drugs, and facilitate expulsion of urinary calculi. The mechanism of action of indomethacin is discussed in terms of its analgesic and anti-inflammatory effects and its prostaglandin synthesis inhibition. PMID:3720020

  8. IL-1, IL-4 production and IgE levels in acute and chronic fasciolosis before and after triclabendazole treatment.

    PubMed

    Allam, A F; Osman, M M; el-Sayed, M H; Demian, S R

    2000-12-01

    IL-1 generation by mononuclear phagocytes, IL-4 production by Th2 lymphocytes and IgE levels in serum were measured in eight patients with acute fasciolosis and seven patients in the chronic stage of the disease before and after triclabendazole treatment. Results were compared with those of a control group of ten individuals. The monocytes and lymphocytes from patients with acute and chronic fasciolosis produced significantly lower levels of IL-1 and IL-4 respectively, particularly in the chronic phase of the disease, as compared to the control. A significant increase in IgE level in both acute and chronic fasciolosis was observed. The level was significantly higher in acute as compared to chronic cases. After treatment with triclabendazole IL-1, IL-4 and IgE levels moved towards the control indicating obvious improvement in the immunological responses of the patients. PMID:11198376

  9. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2016-05-19

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  10. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers.

    PubMed

    Kjell, Jacob; Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew; Olson, Lars

    2015-11-01

    With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines--monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)--to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  11. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    PubMed Central

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  12. Minocycline protects PC12 cells against NMDA-induced injury via inhibiting 5-lipoxygenase activation.

    PubMed

    Song, Ying; Wei, Er-Qing; Zhang, Wei-Ping; Ge, Qiu-Fu; Liu, Jian-Ren; Wang, Meng-Ling; Huang, Xiao-Jia; Hu, Xin; Chen, Zhong

    2006-04-26

    Recently, we have reported that minocycline, a semi-synthetic tetracycline with neuroprotective effects, inhibits the in vitro ischemic-like injury and 5-lipoxygenase (5-LOX) activation in PC12 cells. In the present study, we further determined whether minocycline protects PC12 cells from excitotoxicity via inhibiting 5-LOX activation. We used N-methyl-d-aspartate (NMDA, 200 microM) to induce early (exposure for 6 h) and delayed (exposure for 6 h followed by 24 h recovery) injuries. We found that NMDA receptor antagonist ketamine, 5-LOX inhibitor caffeic acid and minocycline concentration dependently attenuated NMDA-induced early and delayed cell injuries (viability reduction and cell death). However, only ketamine (1 microM) inhibited NMDA-evoked elevation of intracellular calcium. In addition, immunohistochemical analysis showed that NMDA induced 5-LOX translocation to the nuclear membrane after 1- to 6-h exposure which was confirmed by Western blotting, indicating that 5-LOX was activated. Ketamine, caffeic acid and minocycline (each at 1 microM) inhibited 5-LOX translocation after early injury. After delayed injury, PC12 cells were shrunk, and 5-LOX was translocated to the nuclei and nuclear membrane; ketamine, caffeic acid and minocycline inhibited both cell shrinking and 5-LOX translocation. As a control, 12-LOX inhibitor baicalein showed a weak effect on cell viability and death, but no effect on 5-LOX translocation. Therefore, we conclude that the protective effect of minocycline on NMDA-induced injury is partly mediated by inhibiting 5-LOX activation. PMID:16574083

  13. A controlled Nordic multicentre study of zuclopenthixol acetate in oil solution, haloperidol and zuclopenthixol in the treatment of acute psychosis.

    PubMed

    Baastrup, P C; Alhfors, U G; Bjerkenstedt, L; Dencker, S J; Fensbo, C; Gravem, A; Pedersen, V; Elgen, K; Brekke, B; Fredslund-Andersen, K

    1993-01-01

    Zuclopenthixol acetate--a new injectable formulation with a duration of action of 2-3 days--was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed, psychotic patients. The patients were stratified into 3 diagnostic categories: acute psychoses (48 patients), mania (22 patients), and exacerbation of chronic psychoses (73 patients). The patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Mania Rating Scale (BRMAS) (only manic patients) and globally on the Clinical Global Impression (CGI). The study was an open, randomized multicentre trial with a 6-day treatment period. The zuclopenthixol acetate patients received 1-4 doses, the haloperidol patients 1-26 and the zuclopenthixol patients 1-22 doses. The assessments on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories, with no differences between treatments. The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments. All 3 treatments caused a rapid remission of symptoms on the BRMAS. Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments. Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients. PMID:8093824

  14. Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food. This retrospective cohort study compared data from the treatment of two groups of children in Malawi aged 6-59 months w...

  15. Availability of Diagnostic and Treatment Services for Acute Stroke in Frontier Countie