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Synthetic Approaches to Inhibitors of Isoprenoid Biosynthesis
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Pedro Merino, Loredana Maiuolo, Ignacio Delso, Vincenzo Algieri, Antonio De Nino, Tomas Tejero
Analogues of alendronic acid (49) were prepared through an optimized three-step methodology. The protection of the 1-hydroxy group was necessary for avoiding mixtures in the acylation step (Scheme 2.15) (Vachal et al., 2006).
Corticosteroids
Published in Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer, Handbook of Systemic Drug Treatment in Dermatology, 2015
Bisphosphonates are the agents of choice for treatment and prevention of osteoporosis. They slow the rate of bone turnover. Alendronic acid or risedronate sodium (given daily or once a week) are first-choice drugs and disodium etidronate is an alternative (given in 2-week cycles every 13 weeks).
Case 30: Oral Ulceration
Published in Iqbal Khan, Medical Histories for the MRCP and Final MB, 2018
Greet the patient and introduce yourself.Invite the patient to tell you about his medical problems. Enquire when he first noticed the ulcer and whether it is painful. Is it recurrent? Has it increased in size? Has he noticed any enlarged lymph nodes? Are there any constitutional symptoms? Ask about ulceration in other parts of the body, e.g. genital ulcers.Past medical history. Has he ever been diagnosed with conditions such as Crohn’s disease, celiac disease and Behçet’s disease?Drug history and allergies. Drugs such as NSAIDs, nicorandil and alendronic acid are associated with oral ulceration.Take the social history. Alcohol and tobacco consumption are associated with an increased risk of oral cancer and hence the risk should be quantified by asking about the amount and duration of use of these drugs. Poor oral hygiene also constitutes a risk factor and it would be worth asking about this.Family history. Enquire about the family history of Crohn’s disease. Is it a secure diagnosis?Make the systems enquiry.Now confirm that the information is correct and create a problem list and a possible management plan.
Aortic valve stenosis: drivers of disease progression and drug targets for therapeutic opportunities
Published in Expert Opinion on Therapeutic Targets, 2022
Giuseppe Pinto, Gabriele Fragasso
The degree of valvular calcifications is directly associated to severity of calcific AS. As previously described, calcification of aortic valve has been frequently encountered as a predictor of AS progression. On the contrary, the association of serum calcium levels and calcium-phosphate metabolism with AS progression remains to be established. Whether an increased bone reabsorption, as occurring in osteoporosis, is linked to an increased calcification of aortic valve is not fully understood. For this reason, some retrospective studies have tried to evaluate the role of bisphosphonates, at present first line drugs for osteoporosis as they inhibit bone reabsorption. Unfortunately they have provided inconclusive results [124–126]. More recently, denosumab, an antibody binding to osteoblast-produced receptor activator of nuclear factor-kappaB ligand (RANKL), whose function is to decrease bone resorption and turnover by reducing RANKL binding to the osteoclast receptor RANK, has been tested in vitro showing a reduction in aortic VIC calcification [127]. Unfortunately, these promising results have not been confirmed in a recent double-blind randomized controlled trial testing denosumab or alendronic acid versus placebo. Neither of these two drugs have slowed progression of aortic valve calcification in patients with calcific AS [128].
Facing the future: challenges and opportunities in adoptive T cell therapy in cancer
Published in Expert Opinion on Biological Therapy, 2019
Isabelle Magalhaes, Claudia Carvalho-Queiroz, Ciputra Adijaya Hartana, Andreas Kaiser, Ana Lukic, Michael Mints, Ola Nilsson, Hans Grönlund, Jonas Mattsson, Sofia Berglund
The defective tumor vasculature could also be exploited for drug delivery. Tumor tissues are subject to the enhanced permeability and retention effect, where the leaky vessels allow accumulation of nanoparticles into the tumor, while decreased lymphatic drainage inhibits their removal. Through engineering nanoparticles of a size suited to pass through the gaps in the leaky tumor vasculature, but too large to enter through normal endothelial gaps, preferential tumor accumulation could be achieved [126]. An example of how this principle can be used is found in a study where alendronic acid in a liposomal formulation was used to selectively sensitize tumor tissue to eradication by adoptively infused γδ T cells in a mouse model [127].
Sweat rate and sweat composition following active or passive heat re-acclimation: A pilot study
Published in Temperature, 2021
Lisa Klous, Cornelis de Ruiter, Puck Alkemade, Hein Daanen, Nicola Gerrett
Fifteen non-acclimatized participants visited the laboratory for the same controlled hyperthermia (CH) HA protocol, followed by a 28-day decay period. Thereafter, participants were divided over three HRA groups: six of them were re-exposed to CH (CH-CH), five to hot water immersion (CH-HWI) and four were control (CH-CON); Table 1). Based on their peak oxygen uptake (VO2peak), peak power output and training frequency, participants were either classified as recreationally trained or trained (Table 1) [25,26]. No significant differences were observed between participant characteristics (Table 1). Participants had not encountered hot air temperatures (> 25°C) for > 3 months, were nonsmokers, had no history of heat-related illnesses, cardiovascular complications and did not have any known issues with thermoregulation. Only the female participant in CH-CON was taking medication (70 mg alendronic acid weekly, 500 mg calci-chew and 7.5 mg mirtazapine daily) throughout the study. Female menstrual cycle phase was recorded but not controlled for as this would have been unfeasible given the required timing of each part of the protocol (10-day HA, 28-day decay and 5-day HRA consecutively). Furthermore, participants were instructed to refrain from alcohol and strenuous exercise 24 h prior to the experiments, to avoid excessive caffeine consumption during the entire protocol, and to refrain from caffeine and fast 2 h prior to testing. To promote hydration, participants were asked to consume 500 mL of water the night before the experiments and another 10 mL·kg−1 body mass of water in the 3 h prior to the experiment. Participants replicated their food and fluid intake starting 24 h before each HST.