Cardiovascular and Hematological Agents in Medicinal Chemistry最新文献

Introduction: Hypoglycemia and anemia are associated with diabetes mellitus. Medicinal plants and orthodox drugs have been used for the management of this disease. This study aimed to validate the ethnomedical claims of Terminalia catappa Linn. leaf extract in reducing hyperglycemia and hematological potentials in alloxan-induced diabetic rats and to identify likely antidiabetic compounds.

Materials and methods: Ultra-high-performance liquid chromatography was used to identify the various phytochemical constituents. Male Wistar rats were randomly divided into five groups containing 6 rats per group. Group 1 (control) received 0.2 ml/kg of distilled water, group 2 received 130 mg/kg of T. catappa aqueous extract, groups 3-5 were diabetic and received 0.2 ml/g distilled water, 130 mg/kg T. catappa extract and 0.75 IU/kg insulin respectively for 14 days. Hematological parameters were measured and an oral glucose tolerance test was carried out using 2 g/kg body weight glucose. A histological analysis of the pancreas was done.

Results: Twenty-five compounds identified as flavonoids, phenolic acids, tannins, and triterpenoids were detected. The blood glucose levels were significantly (p <0.05) elevated in DM groups but were significantly (p <0.05) reduced following Terminalia catappa leaves extract to DM groups. There was s significant (p <0.05) increase in insulin levels improved hematological parameters (RBC, WBC, and platelets), and increased islet population.

Conclusion: These results suggest that T. catappa extract has hypoglycemic, insulinogenic, and hematopoietic potentials in diabetic condition and offer protection to the pancreas which could be attributed to the phytochemical constituents thereby justifying its use in traditional therapy.

Background: Advances in organ transplantation were made after the discovery of the pure form of cyclosporine by Dr Jean Borel in the 1970s. In fact, in clinical practice achieving a delicate balance in circulating immunosuppressive necessitate focus on the difficult task of posttransplant therapeutic drug monitoring.

Objective: The purpose of this study was to determine the pharmacologic properties of cyclosporine- tacrolimus, detection methods, and the effects on the activity of cytochrome P450 enzymes when prescribing the most efficient treatments in forms of polypharmacy for the recipients of heart transplantation.

Methods: Scientific literature on the interactions of tacrolimus and cyclosporine with human cytochrome P450 enzymes was searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus.

Results: Prescription immunosuppressive drugs based on polypharmacy accompanied by induction agents could result in hidden neurotoxicity and nephrotoxicity. A literature search shows that cyclosporine prescription with antihypertensives drugs needs close monitoring. Co-administration of tacrolimus and diltiazem or verapamil needs a decrease in the tacrolimus dose by 20-50%. Vigilant attention to the lowest possible statin dose is needed when coadministered with fluvastatin or pravastatin. Polypharmacy based on ticlopidine, clopidogrel, and cyclosporine or tacrolimus needs monitoring of immunosuppressive drug levels for several months. A prescription with clotrimazole or fluconazole needs close monitoring, and itraconazole or ketoconazole needs to reduce the initial dose by 50%. Combination with nefazodone needs to be avoided, and alternative drugs such as sertraline or citalopram could be prescribed in addition to further monitoring consideration. In prescription with phenytoin, the bound and free phenytoin levels need close monitoring.

Conclusion: Polypharmacy based on tacrolimus or cyclosporine needs vigilant therapeutic drug monitoring due to the cytochrome P450 enzymes associated with biochemical variables in metabolic pathways. Further attention to polypharmacy should be given to circulate drugs that could hide pharmacokinetics interactions associated with infections, malignancies, chronic kidney disease, and rejection after organ transplantation.

Background: Dysbiosis of the gastrointestinal microbiota is not only related to the pathogenesis of intestinal disorders but also associated with extra-intestinal diseases. Various studies have revealed the role of an imbalance of intestinal microbiota and their metabolites including bile acids, indole derivatives, polyamines, and trimethylamine in the progression of various diseases. The elevated plasma level of the oxidized form of trimethylamine is associated with the increased risk of cardiovascular diseases. Literature supports that herbal medicines can modulate human health by altering the diversity of gut microbiota and their metabolites and proposes the use of prebiotics to improve dysbiotic conditions as a new way of therapeutic strategy.

Methods: In silico studies including drug likeliness, toxicity prediction, and molecular interaction of phytochemicals against trimethylamine lyase enzyme have been done. Antimicrobial activity of extracts of selected plant i.e. Syzygium aromaticum was done by disc diffusion and the protective effects of plant compounds were examined on trimethylamine-n-oxide a bacterial metabolic product and high glucose induced toxicity.

Results: The current study has found that the phytochemicals of S. aromaticum identified as nontoxic and followed the standard rules of drug likeliness and showed a significant binding affinity against trimethylamine-n-oxide producing enzymes. Furthermore, S. aromaticum extract was found to have antimicrobial potential and cardioprotective effects by reducing the production of intracellular reactive oxygen species and correcting the distorted nuclear morphology in the presence of high trimethylamine-n-oxide.

Conclusion: Conclusively, our study explored the herbal intervention in intestinal dysbiosis and suggested a natural therapy against dysbiosis associated with cardiac disease, and S, aromaticum was found to have exceptional cardioprotective potential against TMAO induced gut dysbiosis, which provides a novel future therapeutic intervention for treating cardiovascular complications.

Background: Sepsis is a significant cause of mortality worldwide. This study aimed to compare clinical and laboratory characteristics of sepsis in patients addicted to illicit drugs versus patients with no illicit drug addiction.

Methods: In this cross-sectional study, all patients hospitalized with sepsis diagnosis were recruited within six months from September to March 2019. Sixty patients for each group (illicit drugaddicted and non-addicted individuals) were selected. The data relating to illicit drug consumption, serum indices, the current focus of infection, duration of hospitalization, and disease outcomes were collected. Patients who had an illicit drug addiction were compared with non-addicted patients in terms of clinical and laboratory parameters. The data collected were analyzed using SPSS software (version 19).

Results: The bacterial load in the urine culture was statistically significant in both groups and higher in the non-addicted group. The frequency distributions of focus of infection, duration of hospitalization, and outcome were not significantly different between the two groups. The serum sodium and total neutrophils were significantly higher in the addicted group. However, the MCHC level was significantly lower (p < 0.05).

Conclusion: Opium may have stimulated the immune system and reduced bacterial infection in septic patient users.

Aims: This study aimed to evaluate the hepatotoxicity of buprenorphine in lactating rat pups of buprenorphine-injected mothers. Buprenorphine (BUP), a semisynthetic opioid, is increasingly administrated as a first-line standard maintenance treatment for opioid dependence due to its high safety and efficacy compared to other opioids. Numerous studies have confirmed the safety of BUP maintenance treatment in addicted patients.

Objectives: This study was designed to assess the effects of BUP on the activities of liver enzymes, oxidative parameters, and liver histopathological changes in pups born to a mother exposed to this drug during lactation.

Methods: BUP at a dose of 0.5 or 0.1 mg/kg was subcutaneously administrated to lactating rats for 28 days. At the end of the experiment, the pups were anesthetized, and blood samples were obtained from their hearts for measuring liver enzymes. Then the livers of the animals were dissected to measure oxidative stress parameters. In addition, the liver samples were fixed for histopathological evaluation.

Results: The findings indicated a decrease in the activities of serum liver enzymes (ALT and AST) of the pups born to mothers exposed to 0.5 and 1 mg/kg of BUP during lactation. BUP could not change malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, nor superoxide dismutase (SOD) activity in the liver tissue of animals. Some vacuolated hepatocytes with dark, eccentric nuclei, necrosis with karyolytic nuclei, mitotic figures, and multiple binucleated cells were seen in the pups which received 1 mg/kg of BUP.

Conclusion: In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation.

Introduction: Natural medicine (NM) has been used since ancient times for therapeutic purposes worldwide. Presently, the combination of clopidogrel and NM with a reasonable synergistic effect has gained increasing acceptance in clinical therapeutics.

Methods: Here, we have performed a comprehensive retrieval of literature published in both English and Chinese databases until August 1, 2022, studying the synergistic interactions of clopidogrel and NM through pharmacokinetic/pharmacodynamic (PK-PD) analyses. We retrieved 7, 3, and 5 studies on PK analysis and 3, 3, and 8 studies on PD analysis for the interaction of clopidogrel with single herbal medicines, bioactive compounds, and herbal prescriptions, respectively. Most studies on NM have been found to mainly focus on preclinical observations, and there have been fewer clinical PK analyses.

Results: A potential drug-herb interaction has been observed to occur when clopidogrel and NM were metabolized by an enzyme network comprising P-gp, CES1, and CYP450. In contrast, most PD studies have focused on clinical observations, and few preclinical findings have been reported. Some cases have suggested that the combination of the two types of drugs would alter the antiplatelet efficacy and adverse effects. Studies on PK, however, have shown significant or slightly varying results for the drug prototype and its metabolites.

Conclusion: In the combination therapies, the interaction between clopidogrel and NM was found to alter antiplatelet aggregation pathways and P2Y12 receptor function.

Introduction: Myeloproliferative neoplasms (MPNs) are divided into BCR-ABL positive Chronic myeloid leukemia (CML) and BCR-ABL negative MPNs including Polycythemia vera (PV), Essential Thrombocythemia (ET) and Primary myelofibrosis (PMF). Evaluation of the Philadelphia chromosome in MPNs is a diagnostic requirement for classic CML.

Case report: In 2020, a 37-year-old woman with negative cytogenetic testing for Janus kinase2 (JAK2), Calreticulin (CALR), myeloproliferative leukemia virus oncogene (MPL), and positive for BCR-ABL1 mutation with reticular fibrosis in bone marrow was diagnosed as CML. Some years ago, the patient had been diagnosed with PMF with evidence of histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease (KFD). The BCR-ABL fusion gene was initially evaluated which was negative. Then, Cutaneous squamous cell carcinoma (cSCC) was confirmed by Dermatopathologist with palpable splenomegaly and high white blood cell (WBC) count with basophilia. Finally, BCR-ABL was detected positive by the fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR). In fact, the co-occurrence of PMF with CML was identified.

Conclusion: This case study highlighted the importance of some cytogenetic methods in the detection and classification of MPNs. It is recommended that physicians pay more attention to it and be aware of the planning treatment.

Hypothermia and autophagy are critical regulators of cell homeostasis by regulating intra and intercellular cell communication. Myocardiocyte cryotherapy poses multiple cellular and subcellular effects on the injured cell, including upregulation of autophagy. Autophagy plays a crucial role in modifying cell metabolism by regulating downregulation, reducing reactive oxygen species production, and improving the natural cellular antioxidant defense system. Reduction of reactive oxygen species production and improving natural cellular antioxidant defense system. Therapeutic hypothermia ranges from 32-34°C in terms of local myocardiocyte cooling. Hypothermia induces autophagy by phosphorylating the Akt signaling pathway. Hypothermia has a more therapeutic effect when applied at the beginning of reperfusion rather than in the beginning of ischemia. Moderate hypothermia with 33°C poses most therapeutic effect by viability maintaining and reduction of reactive oxygen species release. Application of local hypothermia to myocardiocytes can be applied to infarcted myocardiocytes, anginal and to the cardiomyopathies.

Objectives: To assess acute lipid profiles, atrial fibrillation and other cardiovascular risk factors in patients undergoing treatments by thrombectomy (EVT) with acute ischemic stroke (AIS).

Methods: We performed a retrospective analysis of the lipid profile and vascular risk factor in 1639 consecutive patients with acute ischemic stroke between January 2016 and December 2021. To assess lipid profiles, laboratory tests, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were obtained the day after admission. We also examined the association between lipid profile, AF and EVT in multivariate logistic regression analysis.

Results: Median age of patients was 74 years, 54.9% were males (95% CI 52.5-57.4%), and 26.8% (95% CI, 24.7-29.0%) had AF. EVT patients (n = 370; 22.57 %; 95% CI, 20.6-24.7) showed no difference in age (median 73 years (IQR; 63-80) versus 74 years (IQR; 63-82)), HbA1c levels (median 5.8 (IQR; 5.4-6.2) versus 5.9 (IQR; 5.4-6.4)), TG/HDL ratio (median 2.40 (IQR; 1.65-3.48) versus 2.51 (IQR; 1.73-3.64)), diabetes (OR 0.82; 95% CI 0.61 to 1.08), hypertension (OR 0.87; 95% CI 0.68 to 1.12) and obesity (OR 1.06; 95% CI 0.78 to 1.42) compared to non-EVT patients. Conversely, EVT patients showed lower levels of TC (160 mg/dl (IQR; 139- 187) versus 173 mg/dl (IQR; 148-202); p <0.001), LDL-C (105 mg/dl (IQR; 80-133) versus 113 mg/dl (IQR; 88-142); p <0.01), TG (98 mg/dl (IQR; 76-126) versus 107 mg/dl (IQR; 85-139); p <0.001), non-HDL-C (117 mg/dl (IQR; 94-145) versus 127 mg/dl (IQR; 103-154); p <0.001), HC (8.3 mmol/l (IQR; 6-11) versus 10 mmol/l (IQR; 7.3-13.5); p <0.001) than non-EVT patients. Multivariate logistic regression analysis showed an independent association of EVT with TC (OR 0.99, 95% CI 0.98-0.99), AF (OR 1.79, 95% CI 1.34-2.38), age (OR 0.98, 95% CI 0.96-0.99), and NIHSS (OR 1.17, 95% CI 0.14-1.19).

Conclusion: Total cholesterol and all cholesterol-related measures were significantly lower in patients undergoing thrombectomy than in other stroke patients. Conversely, we found that AF was significantly high in patients with EVT, suggesting that hypercholesterolemia could be mainly linked to small-vessel occlusion stroke while large vessel occlusion (LVO) stroke could show different causes. AIS patients may have different pathogenesis and their understanding may improve the discovery of specific and tailored preventive treatments.