Bacopa monnieri: Historical aspects to promising pharmacological actions for the treatment of central nervous system diseases

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieriin the central nervous system. It reviewed articles on B. monnieriusing Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieriimproves learning and memory and presents biological effects against Alzheimer’s disease, Parkinson’s disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnierihave been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.

Formulation, Preparation, Characterization, and Evaluation of Dicarboxylic Ionic Liquid Donepezil Transdermal Patches

Donepezil (DPZ) is generally administered orally to treat Alzheimer’s disease (AD). However, oral administration can cause gastrointestinal side effects. Therefore, to enhance compliance, a new way to deliver DPZ from transdermal patch was developed. Ionic bonds were created by dissolving dicarboxylic acid and DPZ in ethanol, resulting in a stable ionic liquid (IL) state. The synthesized ILs were characterized by differential scanning calorimetry, optical microscope, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The DPZ ILs were then transformed to a suitable drug-in-adhesive patch for transdermal delivery of DPZ. The novel DPZ ILs patch inhibits crystallization of the IL, indicating coherent design. Moreover, DPZ ILs and DPZ IL patch formulations performed excellent skin permeability compared to that of the DPZ free-base patch in both in vitro and ex vivo skin permeability studies.

A survey of patients with laryngotracheal stenosis on future clinical trial design

Background/Aims Laryngotracheal stenosis is a rare but devastating proximal airway fibrosis that restricts a patient’s ability to breathe. Treatment is primarily surgical and to date, there has never been a multi-institutional, randomized, prospective, and interventional clinical trial for a medical therapy to treat laryngotracheal stenosis. Therefore, we aimed to obtain patient feedback to guide successful trial design, recruitment, retention, and for identifying potential barriers to study participation. Methods Over 1000 members of an international laryngotracheal stenosis online support community (the Living with Idiopathic Subglottic Stenosis Facebook group) were sent two questionnaires for a proposed interventional double-blinded, randomized, placebo-controlled clinical trial. Results A total of 317 and 558 participants responded to the first and second surveys, respectively. The majority of participants (77%) were willing to consider enrollment, regardless of having a 50% chance of receiving placebo versus treatment (78%). The majority (84%) of participants were willing to travel 200 miles to participate for up to six in-person visits over 50 days. Specific side effects, including anemia/thrombocytopenia (72%) or risk of infection (69.3%) had the greatest impact on clinical trial participation with other side effects (peripheral edema (53%), oral ulcers (51%), and gastrointestinal side effects (41%)) having less impact. Conclusion Patients with laryngotracheal stenosis possess nuanced insight into their disease and treatment options. As a group, they are extremely motivated for better therapies. Future laryngotracheal stenosis clinical trials should focus on providing excellent side effect -related education and utilizing feedback from online advocacy groups to optimize recruitment and retention.

Decrease in the efficacy of glucagon-like peptide-1 receptor agonists: what is the reason?

The review deals with the drugs of a group of glucagon-like peptide-1 receptors agonists (GLP-1RA) the action of which is based on the incretin effect. In addition to insulinotropic and glucagonostatic action, GLP-1RA contributes to the improvement of glycemic control, a decrease in body weight, and also reduces cardiovascular effects in diabetic patients. The members of this group are divided into short- and long-acting preparations that is determined by their pharmacodynamic properties. Studies have shown that the long-acting GLP-1RA, which are administered once a week, demonstrate better glycemic control with a similar or less risk of the hypoglycemia and gastrointestinal side effects than their short-acting analogues. However, with long-term use of GLP-1RA, there is a reduction in the hypoglycemic action associated with a decrease in the inhibition of intestinal motility due to the phenomenon of tachyphylaxis (desensitization) of the GLP-1 receptors as a result of the vagus nerve activation. Promising means to overcome this shortcoming are considered, such as the development of modified and combined coagonists of dipeptidyl peptidase 1 receptors, as well as oral forms of GLP-1RA. In addition, we have described possible mechanisms influencing the effectiveness of GLP-1RA due to the production of antibodies to various drugs in this group, and the relationship between the effects of incretin mimetics with the state of the intestinal microbiota. In conclusion, the group of incretin-based drugs provides broad perspectives for use in type 2 diabetic patients, with the possibility of correction of both basal and prandial glycemia, and new efficient and safe forms of drugs of this group are actively creating.

Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?”

Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients’ dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action.

Adherence to treatment and prevalence of side effects when medical abortion is delivered via telemedicine

BackgroundThe Scottish government introduced legislation during the COVID-19 outbreak to permit medical abortion at home with telemedicine. All women received an initial telephone consultation. For those choosing medical abortion, we provided self-administered medications to eligible women with pregnancies under 12 weeks’ gestation.AimsTo assess adherence to the recommended abortion drug regimen, with particular focus on the number of misoprostol doses used and the interval between mifepristone and misoprostol administration and the induction–expulsion interval. Additionally, to evaluate use of analgesia, antiemetics and antibiotics, and the side effects, pain and bleeding profile of medical abortion at home.MethodsWe conducted a prospective cohort study of 663 women choosing medical abortion at home via telemedicine at an NHS abortion service in Edinburgh, Scotland between 1 April and 9 July 2020. Interviewer-administered questionnaires were completed at telephone follow-up 4 and 14 days following treatment. Outcome measures were self-reported and included use of mifepristone and misoprostol, induction–expulsion interval (time from misoprostol administration until expulsion of pregnancy), antiemetics, antibiotics, analgesia use, pain scores, rates of side effects, bleeding and preparedness for treatment.ResultsAmong the respondents, 652/663 women (98%) answered at least one questionnaire, and 594/663 (89.6%) used both abortion medications as directed (24–72 hours between medications). The mean (SD) induction–expulsion interval was 4.3 (4.3) hours. Antiemetics were used by 611/663 (92%), 383/599 (64%) completed the course of prophylactic antibiotics, and 616/663 (93%) used analgesia, with mean (SD) worst-pain scores of 6.7 (2.2) out of 10. Regarding side effects, 510/663 (77%) experienced either nausea, vomiting, diarrhoea or headache, 101/663 (15%) experienced headache and 510/663 (77%) experienced bleeding that was heavier than a period; 554/663, (84%) felt prepared for their treatment by teleconsultation.ConclusionPatients are able to correctly self-administer abortion medications following a telemedicine consultation. Further research is required to optimise pain management and gastrointestinal side effects during medical abortion.

Lactobacillus reuteri Alleviates Gastrointestinal Toxicity of Rituximab by Regulating the Proinflammatory T Cells in vivo

Rituximab (RTX) is a widely used anticancer drug with gastrointestinal side effects, such as nausea, vomiting, and diarrhea. The reason for these side effects is still poorly understood. Previous studies have reported that the intestinal microbiota is associated with the occurrence of disease and the therapeutic effect of drugs. In this study, we observed mucosal damage, inflammatory cell infiltration and increased intestinal inflammatory factor expression in RTX-treated mice. RTX also changed the diversity of the intestinal microbiota in mice, and decreased abundance of Lactobacillus reuteri was observed in RTX-treated mice. Further experiments revealed that intragastric administration of L. reuteri in RTX-treated mice attenuated the intestinal inflammatory response induced by RTX and regulated the proportion of helper T (Th) cells. In conclusion, our data characterize the effect of the intestinal microbiota on RTX-induced intestinal inflammation, suggesting that modifying the gut microbiota may represent a positive strategy for managing adverse reactions.

A case of denosumab-associated hyperparathyroidism: A differential diagnostic challenge

Denosumab is a relatively new medicine that has become the second option in the treatment of biphosphonate-resistant or intolerant osteoporosis. Subcutaneous injection with 6-month intervals, approval of its usage in stage 3-4 CKD and not having gastrointestinal side effects are advantages of denosumab. However, it has some disadvantages like requiring monitoring serum levels of calcium and vitamin D before each injection.

Taxane-Induced Upper Gastrointestinal Bleeding

Docetaxel is a taxane, which is a class of chemotherapy agent used in the treatment of multiple malignancies. It is known to have gastrointestinal side effects which can range from mild symptoms such as nausea and diarrhea to more severe complications such as neutropenic enterocolitis. In the current literature, taxanes have not been described to cause upper gastrointestinal bleeding and melena. Here, we present a case of a 54-year-old woman with breast cancer who developed dizziness, fatigue, and melena after receiving chemotherapy. Esophagogastroduodenoscopy revealed diffuse gastric erosions as well as ulceration and linear superficial lesions in the duodenum; biopsies from these sites showed taxane-induced toxicity. Her bleeding resolved with medical therapy and subsequent removal of docetaxel from her chemotherapy regimen. This case identifies upper gastrointestinal bleeding as a previously undescribed side effect of docetaxel therapy. Recent docetaxel use should be included in the differential diagnosis for upper gastrointestinal bleed, and diagnosis should lead to consideration of cessation of docetaxel or substitution with another chemotherapeutic agent.