scholarly journals Adrenergic Modulation with Photochromic Ligands

2020 ◽  
Author(s):  
Davia Prischich ◽  
Alexandre M. J. Gomila ◽  
Santiago Milla-Navarro ◽  
Gemma Sangüesa ◽  
Rebeca Diez-Alarcia ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Respiratory Rate ◽  
Vascular Tone ◽  
Systemic Administration ◽  
On Demand ◽  
Adrenergic Drugs ◽  
Pupillary Responses ◽  
Adrenergic Modulation

Adrenoceptors are ubiquitous and regulate heart and respiratory rate, digestion, metabolism, and vascular tone. They can be activated or blocked with adrenergic drugs, but systemic administration causes broad adverse effects. We have developed photochromic ligands (adrenoswitches) to switch on and off adrenoceptor activity on demand at selected locations. Their pharmacology, photochromism, bioavailability and lack of toxicity allow photomodulating adrenergic signalling, as demonstrated by controlling locomotion in zebrafish and pupillary responses in blind mice.

scholarly journals Adrenergic Modulation with Photochromic Ligands

2020 ◽  
Author(s):  
Davia Prischich ◽  
Alexandre M. J. Gomila ◽  
Santiago Milla-Navarro ◽  
Gemma Sangüesa ◽  
Rebeca Diez-Alarcia ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Respiratory Rate ◽  
Vascular Tone ◽  
Systemic Administration ◽  
On Demand ◽  
Adrenergic Drugs ◽  
Pupillary Responses ◽  
Adrenergic Modulation

Adrenoceptors are ubiquitous and regulate heart and respiratory rate, digestion, metabolism, and vascular tone. They can be activated or blocked with adrenergic drugs, but systemic administration causes broad adverse effects. We have developed photochromic ligands (adrenoswitches) to switch on and off adrenoceptor activity on demand at selected locations. Their pharmacology, photochromism, bioavailability and lack of toxicity allow photomodulating adrenergic signalling, as demonstrated by controlling locomotion in zebrafish and pupillary responses in blind mice.

The Use of Methotrexate in Rheumatoid Arthritis

1985 ◽  
Vol 19 (5) ◽  
pp. 349-358 ◽  
Author(s):  
Peter W. Letendre ◽  
Douglas J. DeJong ◽  
Donald R. Miller
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Folic Acid ◽  
Side Effects ◽  
Adverse Effects ◽  
Systemic Administration ◽  
Refractory Disease ◽  
Controlled Clinical Trials ◽  
Folic Acid Antagonist ◽  
Acid Antagonist

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

Two Strategies of Stem Cells Mobilization Using Plerixafor and Comparison of Grafts Obtained with and without It. Is Plerixafor Only a Mobilization Agent?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4385-4385
Author(s):  
Michal Zwiewka ◽  
Zdenka Stefanikova ◽  
Katarína Masárová ◽  
Ján Martinka ◽  
Mikuláš Hrubiško ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Adverse Effects ◽  
Peripheral Blood ◽  
First Line ◽  
Term Survival ◽  
On Demand ◽  
Cd34 Cells ◽  
Poor Mobilizers ◽  
Better Than

Abstract Abstract 4385 Introduction: Successful autologous peripheral blood stem cell transplantation (aPBSCT) is critical for long-term survival and quality of life in patients with multiple myeloma (MM). Standard mobilization of PBSCs is in 15 to 20% of MM patients inefficient. Better mobilization response is achieved by adding plerixafor to current mobilization regimens. Based on studies it is possible to reduce these numbers to 2%. Methodology: During the period from 06/2009 to 08/2011 our department mobilized five patients with MM using plerixafor, of whom three were remobilized using standard G-CSF + plerixafor scheme (G+P) after a previous unsuccessful mobilization with cyclophosphamide + G-CSF (C+G). Two patients received plerixafor on demand in a failed first-line mobilization attempt (C+G+P). Comprehensive statistical analysis of products mobilized with plerixafor (8 products) versus products obtained using C+G regime alone (40 products) was performed comparing smears, colony forming-units (CFUs) and immunophenotype profile. Time to mobilization, pretreatment, used mobilization regime and adverse effects of plerixafor regimes were also analyzed. The ultimate goal of every mobilization - successful transplantation - was also described and analyzed comparing composition of transplanted products with engraftment of white blood cells (WBC), neutrophil granulocytes and platelets. Results: Analysis of the plerixafor group only: 1. Both mobilization strategies (second-line G+P and first-line C+G+P) allowed to collect enough CD34+ cells for one (3 patients) or two (2 patients) transplants. Failure to mobilize using plerixafor has not been recorded. 3 patients successfully received transplants. 2. Based on an analysis of risk factors for determining poor mobilizer 3 patients could be mobilized preemptively using G+P scheme preventing use of controversial cyclophosphamide. 3. Adverse effects were mild and mainly related to G-CSF. In one patient mobilization was stopped after collecting 2.45 ×106/kg because of anxiety. However, we were unable to definitely connect anxiety symptoms to plerixafor. 4. There was a statistically significant increase of leukocytes in peripheral blood observed after adding plerixafor. In 3 patients it allowed the CD34+ cells to rise above 20/μl. Comparative analysis of plerixafor group vs. group of patients mobilized with C+G: 1. Duration of cytopenia after transplantation was comparable and statistically not different. 2. Significantly higher numbers of CD19+ cells after plerixafor administration suggest a possible value of this drug in the treatment of diseases with this marker. 3. Significant reduction of toxic granulation after plerixafor administration may be a proof of lesser number of infectious complications. 4. Significantly lower numbers of younger cell forms and non-significantly higher numbers of mature cells in products mobilized with plerixafor prove a) no cytotoxic effect of plerixafor b) decreased regenerative potential of bone marrow in poor mobilizers even if chemotherapy is used. 5. Significantly lower numbers of CD34+ cells and CFUs in plerixafor mobilized products suggest a worse overall mobilization response in this group. However CFUs have shown to predict stem cells yield better than CD34+ cells alone. 6. The importance of a non-significant decrease in CD56+ cells in plerixafor mobilized products is unclear as co-expression of CD 38/56 does not show any differences. Conclusions: 1. Preemptive first line mobilization with G+P seems to be an important strategy in predicted poor mobilizers which would otherwise be mobilized with C+G(+P). This prevents possible neutropenia and its complications. On demand first line G+P seems to be a good choice in patients that are mobilized with growth factors only as there is no risk of neutropenia. 2. We highly recommend the investigation of CFUs which usually predict stem cells yield better than CD34+ cells alone and may allow transplantation even if CD34+ cells are low. 3. Because aPBSCT is a therapeutic modality with clear benefit for patients with MM, we highly recommend the use of plerixafor in all MM patients where it is impossible to collect sufficient stem cells. According to our investigation, we believe that plerixafor is only starting its career as a mobilization drug. Its most valuable potential may be in curative regimens of diseases which have affinity to bone marrow. Disclosures: No relevant conflicts of interest to declare.

scholarly journals COMPARISON OF DEXMEDETOMIDINE AND MIDAZOLAM-FENTANYL COMBINATION FOR TYMPANOPLASTY UNDER MONITORED ANAESTHESIA CARE

2020 ◽  
pp. 1-3
Author(s):  
Shivankar Azatshatru ◽  
Sanjul Dandona
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Adverse Effects ◽  
Arterial Pressure ◽  
Respiratory Rate ◽  
Hemodynamic Profile ◽  
Sedation And Analgesia ◽  
Anaesthesia Care ◽  
Surgeon Satisfaction

Objective- To compare the sedation, analgesia, hemodynamics effects, surgeon satisfaction and quality of surgical field provided by dexmedetomidine with combination of midazolam and fentanyl. Methods- 100 patients of ASA I or II posted for tympanoplasty were divided into two groups of 50 patients each. Group D received Dexmedetomidine 1 μg/kg intravenously over 10 minutes loading and 0.2 μg/kg/h intravenously maintenance dose. Group MF received intravenously 0.03 mg/kg midazolam plus 1 μg/kg fentanyl over 10 minutes loading dose and normal saline 0.2 ml/kg/h intravenously as maintenance. Heart rate (HR), Mean Arterial Pressure (MAP), Respiratory Rate (RR), level of Sedation and degree of Analgesia were assessed intraoperatively. Surgeon satisfaction with the operative field and quality of sedation was inquired post-operatively with assessment of Pulse Rate (PR), Mean Arterial Pressure (MAP), Respiratory Rate (RR), sedation and duration of analgesia. Results- Dexmedetomidine showed statistically significant decrease in heart rate and mean arterial pressure, better sedation and analgesia intraoperatively needing lesser rescue doses for sedation and analgesia and better surgeon satisfaction and longer duration of analgesia postoperatively. The adverse effects were bradycardia and hypotension with dexmedetomidine and nausea with midazolam-fentanyl. Conclusion- Dexmedetomidine is better than a combination of midazolam-fentanyl for sedation and analgesia for tympanoplasty surgery under monitored anaesthesia care which provides optimal hemodynamic profile, better sedation, analgesia, surgeon satisfaction and minimal adverse effects.

scholarly journals A Simulation-Based Evaluation of a Cargo-Hitching Service for E-Commerce Using Mobility-on-Demand Vehicles

2021 ◽  
Vol 1 (3) ◽  
pp. 639-656
Author(s):  
André Romano Alho ◽  
Takanori Sakai ◽  
Simon Oh ◽  
Cheng Cheng ◽  
Ravi Seshadri ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Spare Capacity ◽  
On Demand ◽  
Passenger Travel ◽  
Simulation Based ◽  
Total Vehicle ◽  
Passenger Flows ◽  
Parcel Deliveries ◽  
Service Vehicles

Time-sensitive parcel deliveries—shipments requested for delivery in a day or less—are an increasingly important aspect of urban logistics. It is challenging to deal with these deliveries from a carrier perspective. These require additional planning constraints, preventing the efficient consolidation of deliveries that is possible when demand is well known in advance. Furthermore, such time-sensitive deliveries are requested to a wider spatial scope than retail centers, including homes and offices. Therefore, an increase in such deliveries is considered to exacerbate negative externalities, such as congestion and emissions. One of the solutions is to leverage spare capacity in passenger transport modes. This concept is often denominated as cargo hitching. While there are various system designs, it is crucial that such a solution does not deteriorate the quality of service of passenger trips. This research aims to evaluate the use of mobility-on-demand (MOD) services that perform same-day parcel deliveries. To test the MOD-based solutions, we utilize a high-resolution agent- and activity-based simulation platform of passenger and freight flows. E-commerce demand carrier data collected in Singapore are used to characterize simulated parcel delivery demand. We explore operational scenarios that aim to minimize the adverse effects of fulfilling deliveries with MOD service vehicles on passenger flows. Adverse effects are measured in fulfillment, wait, and travel times. A case study on Singapore indicates that the MOD services have potential to fulfill a considerable amount of parcel deliveries and decrease freight vehicle traffic and total vehicle kilometers travelled without compromising the quality of MOD for passenger travel. Insights into the operational performance of the cargo-hitching service are also provided.

scholarly journals Safety and Efficacy of Secondary Prophylactic in Patients with Severe Hemophilia Type A and B: A Systematic Review and Meta-Analysis Study

2021 ◽  
Author(s):  
Reza Goudarzi ◽  
Shirin Seraji ◽  
Mohammad Reza Amiresmaili ◽  
Hasan Gharibnavaz
Keyword(s):  
Systematic Review ◽  
Adverse Effects ◽  
Meta Analysis ◽  
Coagulation Factor ◽  
Type A ◽  
Treatment Method ◽  
Severe Hemophilia ◽  
Bleeding Rate ◽  
Safety And Efficacy ◽  
On Demand

Context: Patients with hemophilia receive coagulation factor replacement for a lifetime. In Iran, on-demand treatment method is used as a standard. Clinical studies have shown significant improvements in clinical and economic outcomes as a result of the use of prophylaxis compared with other therapies. The aim of this study was to evaluate the safety and efficacy of prophylaxis in patients with severe hemophilia type A and B. Evidence Acquisition: This is a systematic review and meta-analysis in order to evaluate the safety and efficacy of prophylaxis treatment in patients with severe hemophilia. To this response, all clinical trials, cohorts, and case-control studies, which have been investigated, were published between 1970 to Sep of 2017. STROBE and CONSORT checklists have been used according to the type of study to assess the quality of the study reports, and the results have been analyzed in STATA by meta-analysis methods. Results: A total of 1439 studies were found in primary search and 17 of them had an inclusion criteria. The mean annual bleeding rate in prophylays treatment was 2.8 times per person/year. This study also showed that in prophylaxis, the average incidence of adverse effects was 0.13 cases, and the severe adverse effects was 0.06 cases per person/year. Conclusions: The analysis of the studies entered in this evaluation showed that the adverse effects were significantly lower in patients treated with prophylaxis than in patients treated with on-demand treatment. This difference was observed in severe adverse effect, however, it was not statistically significant; this shows that prophilaxis is safer than the on-demand method. The lower annual bleeding rate in prophylaxis compared with the on-demand treatment method is also a sign of the effectiveness of prophilaxis.

Prospective Randomized Double-Blind Study Comparing l-Epinephrine and Racemic Epinephrine Aerosols in the Treatment of Laryngotracheitis (Croup)

PEDIATRICS ◽  
1992 ◽  
Vol 89 (2) ◽  
pp. 302-306
Author(s):  
Yeheskel Waisman ◽  
Bruce L. Klein ◽  
Douglas A. Boenning ◽  
Grace M. Young ◽  
James M. Chamberlain ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Adverse Effects ◽  
Respiratory Rate ◽  
Double Blind Study ◽  
Double Blind ◽  
Treatment Groups ◽  
Fraction Of Inspired Oxygen ◽  
To Receive ◽  
Inspired Oxygen

Aerosolized racemic epinephrine, but not l-epinephrine, is commonly used in treating croup. The efficacy and adverse effects of nebulized racemic and l-epinephrine in the treatment of laryngotracheitis were compared. Children 6 months to 6 years of age with a croup score of 6 or above were assigned in a randomized double-blind fashion to receive either racemic (n = 16) or l-epinephrine (n = 15) aerosols. Croup score, heart rate, blood pressure, respiratory rate, fraction of inspired oxygen, and oxygen saturation were recorded before treatment and at 5, 15, 30, 60, 90, and 120 minutes after the aerosol. Patients in both groups showed significant transient reduction of the croup score and respiratory rate following the aerosol (P < .001), but there were no differences between treatment groups when croup score, heart rate, blood pressure, and respiratory rate were assessed over time. It is concluded that l-epinephrine is at least as effective as racemic epinephrine in the treatment of laryngotracheitis and does not carry the risk of additional adverse effects. l-Epinephrine is also more readily available worldwide, is less expensive, and can be recommended for this purpose.

Immunoelectron microscope detection of C-type natriuretic peptide in normal human atrial tissue

1993 ◽  
Vol 51 ◽  
pp. 388-389
Author(s):  
Chi-Ming Wei ◽  
Margaret Hukee ◽  
Christopher G.A. McGregor ◽  
John C. Burnett
Keyword(s):  
Amino Acid ◽  
Natriuretic Peptide ◽  
Vascular Tone ◽  
Cardiac Tissue ◽  
Ring Structure ◽  
Terminal Amino Acid ◽  
Amino Acid Peptide ◽  
Normal Human ◽  
Terminal Amino ◽  
The Brain

C-type natriuretic peptide (CNP) is a newly identified peptide that is structurally related to atrial (ANP) and brain natriuretic peptide (BNP). CNP exists as a 22-amino acid peptide and like ANP and BNP has a 17-amino acid ring formed by a disulfide bond. Unlike these two previously identified cardiac peptides, CNP lacks the COOH-terminal amino acid extension from the ring structure. ANP, BNP and CNP decrease cardiac preload, but unlike ANP and BNP, CNP is not natriuretic. While ANP and BNP have been localized to the heart, recent investigations have failed to detect CNP mRNA in the myocardium although small concentrations of CNP are detectable in the porcine myocardium. While originally localized to the brain, recent investigations have localized CNP to endothelial cells consistent with a paracrine role for CNP in the control of vascular tone. While CNP has been detected in cardiac tissue by radioimmunoassay, no studies have demonstrated CNP localization in normal human heart by immunoelectron microscopy.

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