maximal dosage
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2022 ◽  
Author(s):  
C.M. Gant ◽  
M.M. Oosterwijk ◽  
S.H. Binnenmars ◽  
G.J. Navis ◽  
H. Haverkate ◽  
...  

Abstract Objective Pharmacological inhibition of the renin-angiotensin-aldosterone-system (RAASi) is the cornerstone of hypertension treatment, renoprotection and secondary prevention of cardiovascular disease in patients with type 2 diabetes. Although there is a dose-dependent effect of RAASi with optimum protection when using maximal dose, little is known on actual use of maximal dosage RAASi in clinical practice. Here we investigate prevalence of maximal dosage RAASi, and contraindications for, optimizing RAASi dosage, in patients with complicated type 2 diabetes in a real-life clinical setting.Research Design and MethodsWe performed a retrospective analysis in 668 patients included in the DIAbetes and LifEstyle Cohort Twente (DIALECT). We grouped patients according to no RAASi, submaximal RAASi and maximal RAASi use. All potassium and creatinine measurements between January 1st 2000 and date of inclusion in DIALECT were extracted from patients files. We identified determinants of maximal RAASi use vs submaximal RAASi use with multivariate logistic regression analysis. ResultsMean age was 64 ± 10 years and 61% were men. In total, 460 patients (69%) used RAASi, and 30% used maximal RAASi. Maximal RAASi use was not statistically different between different indications for RAASi (i.e. hypertension, diabetic kidney disease, coronary heart disease and cerebrovascular disease; P>0.05). Per patient, 2 [1-4] measurements of potassium and 20 [13-31] measurements of creatinine were retrieved, retrospective follow-up time was -3.0 [-1.4 to -5.7] years. Pre-baseline hyperkalemia >5.0 mmol/l and acute kidney injury were found in 151 (23%) patients and 119 patients (18%), respectively. Determinants of maximal RAASi were prior acute kidney injury (OR 0.51 (0.30-0.87)), increased albuminuria (OR 1.89 (1.17-3.08)) and total number of used antihypertensives (OR 1.66 (1.33-2.06)).ConclusionsMaximal dose RAASi is used in almost one third of complicated type 2 diabetes patients in a real-life setting. The prevalence of contraindications is considerable, but relative in nature, suggesting that it is worthwhile to explore strategies aimed at maximizing RAASi while circumventing the alleged contraindications.


Plants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 21
Author(s):  
Giselle A. Borges e Soares ◽  
Tanima Bhattacharya ◽  
Tulika Chakrabarti ◽  
Priti Tagde ◽  
Simona Cavalu

Essential oils (EOs) have been traditionally used as ancient remedies to treat many health disorders due to their enormous biological activities. As mainstream allopathic medication currently used for CNS disorders is associated with adverse effects, the search to obtain safer alternatives as compared to the currently marketed therapies is of tremendous significance. Research conducted suggests that concurrent utilization of allopathic medicines and EOs is synergistically beneficial. Due to their inability to show untoward effects, various scientists have tried to elucidate the pharmacological mechanisms by which these oils exert beneficial effects on the CNS. In this regard, our review aims to improve the understanding of EOs’ biological activity on the CNS and to highlight the significance of the utilization of EOs in neuronal disorders, thereby improving patient acceptability of EOs as therapeutic agents. Through data compilation from library searches and electronic databases such as PubMed, Google Scholar, etc., recent preclinical and clinical data, routes of administration, and the required or maximal dosage for the observation of beneficial effects are addressed. We have also highlighted the challenges that require attention for further improving patient compliance, research gaps, and the development of EO-based nanomedicine for targeted therapy and pharmacotherapy.


2018 ◽  
Vol 82 (6) ◽  
pp. 621-624 ◽  
Author(s):  
Dean M. DeLuke ◽  
Darriel Cannon ◽  
Caroline Carrico ◽  
B. Ellen Byrne ◽  
Daniel M. Laskin

2018 ◽  
Vol 4 (2) ◽  
pp. 249-255
Author(s):  
Rini Hendari ◽  
Dahlan H Ahmad ◽  
A Haris

Background: Lo'i Karana is one type of traditional therapies that has existed for more than one hundred years in the midst of society of Bima and Dompu to overcome the discomfort due to labor. However, lack of research has been conducted to examine its effect on pain in postpartum mothers.Objective: To examine the effect of Lo’I Karana on muscle pain in postpartum mothers.Methods: This was a quasy experimental study with posttest only control group design. Thirty mothers were selected using purposive sampling, which 10 assigned in 3 groups (standard-dose group, minimal-dose group, and maximal-dose group). Wong-Baker Faces Pain rating scale was used to measure pain on day 1 and day 3. Kruskal-Wallis Test and Mann Whitney test were used for data analysis. Results: There were significant effects of Lo’I karana in minimal, standard and maximal dosage on pain level in the first day (p=0.004) and the third day (p=0.009) in postpartum mothers. The results revealed that the higher doses used for the treatment, the less pain of the mothers will be. Conclusion: Lo’I Karana has a significant effect in reducing pain level in postpartum mothers. It is recommended that this intervention can be applied as a part of nursing intervention in caring postpartum mothers.


2017 ◽  
Vol 13 (6) ◽  
pp. 72 ◽  
Author(s):  
Doloreza Prifti ◽  
Ardian Maçi

This research study intended to provide evidence and proof of the positive effects, that applying of the Bio-Fertilizer Herbagreen produced through nanotechnology has on the agriculture in Albania. There are no doubts that nanotechnology is one of the most relevant innovations not only in agriculture, but also in other scientific fields such as biotechnology, medicine etc. Herbagreen nano-particles are able to directly penetrate plants after being applied, thus becoming immediately part of the plants lifecycle and metabolism. This is due to the new nano- and micro-dimensions of the grinded particles after being treated through TMAC (Tribo-Mechanical Activation of Calcite). This technology does not interfere with the mineral initial composition. It simply grinds the mineral particles in nano-dimensions and by so doing increases sensibly their contact surface. This makes these particles “magically” influence the yield quantity and quality in the treated plants. Based on the experiments performed during two consecutive years on the selected crops of corn and wheat, it was noticed that in addition to a yield increase in the plots treated with this nanotechnology, there was also an increase in the gluten values in wheat, while regarding the percentage values of proteins and lipids it was noted that the values of the treated plots with Herbagreen had the same values of the plots treated with the maximal dosage of chemical fertilizers. It was also concluded, that using of the Herbagreen fertilizers can avoid or reduce the soil and waters contamination caused by only traditional mineral fertilizers use. The financial costs for the treatment can be reduced as well.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2541-2541 ◽  
Author(s):  
Mathilde Roumier ◽  
Louis Terriou ◽  
Mohamed Hamidou ◽  
Antoine Dossier ◽  
Anne Sophie Morin ◽  
...  

Abstract Introduction: The serious consequences of severe, life-threatening bleeding in immune thrombocytopenia (ITP) justify the use of several regimens, including platelet transfusions, high-dose parenteral glucocorticoid and intravenous immunoglobulins. The goal of such treatments is to rapidly elevate the platelet count to a level where the risk of severe bleeding is minimized. We lack experience with the use of thrombopoetin receptor agonists (Tpo-RAs) in this situation of emergency. The aim of this study was to evaluate the safety of the use of romiplostim at maximal dosage in patients with severe bleeding manifestations, who have previously failed to respond to corticosteroids (CST) and intravenous immunoglobulin (IVIg). Patients and Methods: We carried out a multicenter retrospective study in France. We included ITP patients with platelet count < 30 x 109/L.and severe bleeding manifestations, who have failed to respond to corticosteroids and IVIg, and have received a rescue therapy with romiplostim at maximal dosage (ie., 10 mg/kg body weight per week). Failure to treatment was defined according to standardized international criteria and severe bleeding manifestations as a score >8 according to the bleeding score previously reported by our group that take into account cutaneous, mucosal and visceral bleeding. Physicians were interviewed and patients' medical charts collected using the standardized form of the Referral Center for Adult ITP. Complete response (CR) and Response (R) were defined according to standardized international criteria: platelet count > 30x109/L with at least a doubling of the baseline value or >100 x109/L. Non-response (NR) was defined as the absence of platelet count increase >30 x109/L with at least a doubling of the baseline count. Results: Fifteen patients (8 men/7 women) were included in the study. The median age was 68 ± 20.9 years [range 17-92]. Two patients presented secondary ITP according to the international definition criteria. Eleven were newly diagnosed ITP, and 4 chronic ITP. Severe bleeding symptoms were the manifestation of ITP in all cases, with a median bleeding score of 16 [9-28], including 4 intracranial hemorrhage, 2 metrorrhagia, 1 macroscopic hematuria, 3 gastrointestinal bleeding and 1 haemoperitoneum. The median platelet count was 1 [0-4]. All patients had received corticosteroids (1mg/bw/day) including 12 pulses of methylprednisolone and IVIg (median dose 2 g/bw). Twelve have also received 8 mg of vinblastine (1 to 3 injections). Nine received platelet transfusions and 4 received blood tranfusions. One patient had received anti-CD20 therapy (rituximab) the same day as TPO-RA therapy, and another hydroxychloroquine before starting TPO-RA therapy. Romiplostim was started 12 days [range 6-32] in median after the first bleeding episode. At that time bleeding symptoms were severe (>8), and the median platelet count was 4 [1-47]. All received 10 mg/kg body weight of romiplostim (including 3 escalating dose). At day 7 after TPO-RA initiation, 9 patients achieved a CR, 1 patient achieved a R and 5 were still non-responder. At days 14, 10 patients achieved a CR and 5 were still non-responder. During the first month of follow-up, the maximal platelets count among the responders was 590 [range: 312-1169], 9 patients experienced a platelet count > 500 x 109/L. One 51 years old patient, bed bound for a muscular hematoma, experienced a deep vein thrombosis with asymptomatic pulmonary embolism, 13 days after IVIg and 5 days after TPO-RA initiation, with a platelet count of 629.109/L. One patient presented superficial thromboembolism of the arm, 14 days after IVIg and 9 days after TPO-RA initiation with a platelet count of 162.109/L. They were both treated with anticoagulation without complication. After a median follow-up of 10 months, no other TPO-RA-related side effects were observed, TPO-RA was discontinuated in 10 patients. Conclusion: Our study demonstrated the relative safety and the interest of the use of romiplostim at the maximal dose in emergency bleeding situation in patients with failure of conventional therapy. However, risk of venous thromboembolism should be carrefully assess in this situation. Disclosures Terriou: amgen: Consultancy; Novartis: Consultancy.


2016 ◽  
pp. bcr2015213670
Author(s):  
Christos Stefanou ◽  
Lakis Palazis ◽  
Areti Loizou ◽  
Chrystalla Timiliotou
Keyword(s):  

1986 ◽  
Vol 250 (5) ◽  
pp. C779-C791 ◽  
Author(s):  
D. A. Williams ◽  
F. S. Fay

The Ca2+-sensitive dye quin 2 was used to monitor Ca2+ levels and to follow Ca2+ transients in suspensions of isolated toad (Bufo marinus) smooth muscle cells, whose contractile activity was monitored with a Coulter counter. Single cells were not utilized to follow Ca2+ changes involved with contraction because of problems of rapid dye bleaching and due to photosensitization of smooth muscle cells loaded with quin 2. High levels of quin 2 loading (2-5 mM) severely prolonged (time course increase greater than 3 times), or completely inhibited, contractile responses to carbachol or potassium depolarization. Lower levels (less than 1 mM) produced adequate fluorescent signals, even at the single cell level, and allowed contractile responses of normal magnitude, although with somewhat prolonged (2-3 times) time course. Resting Ca2+ concentrations determined using quin 2 at these lower levels were 129 +/- 3 nM, a value that closely coincided with that measured in the same cell type using Ca-sensitive microelectrodes, or an alternate, more highly fluorescent dye, Fura-2. Resting Ca2+ was highly dependent on the extracellular Ca2+ concentration that appeared to effect intracellular Ca2+ (Cai2+) both by altering the driving force on Ca2+ cross the membrane, as well as the Ca2+ permeability of the cell itself. A small but significant relaxation was observed in response to the lowering of cytoplasmic Ca2+ below resting levels. After carbachol or K+ addition, fluorescent transients peaked significantly before the onset of contraction, which was also transient. Isoproterenol, a known relaxant of these cells, caused a small decrease in Cai2+ (approximately 40 nM) below rest, when applied in maximal dosage (10(-4) M). Isoproterenol also consistently diminished the Ca2+ transient induced by excitatory stimuli such as carbachol or K+. These results indicate that changes in contractility may be directly linked to changes in free cytoplasmic Ca2+ in smooth muscle cells.


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