Cardiovascular and Hematological Agents in Medicinal Chemistry最新文献

Background: Reflex cardio-vascular and respiratory (CVR) alterations evoked by intraarterial instillation of nociceptive agents are termed vasosensory reflexes. Such responses elicited by optimal doses of inflammatory mediators have been described in our earlier work.

Objective: The present study was designed to evaluate the interactions between subthreshold doses of inflammatory mediators on perivascular nociceptive afferents in urethane anesthetized rats.

Methods: Healthy male adult rats (Charles-Foster strain) were anesthetized with an intraperitoneal injection of urethane. After anesthesia, the right femoral artery was cannulated. Respiratory movements, blood pressure, and electrocardiogram were recorded. The interactions between subthreshold doses of algogens in the elicitation of vasosensory reflex responses were studied by instillation of bradykinin (1 nM) and histamine (100 μM) into the femoral artery one after the other, in either temporal combination in separate groups of rats. The CVR responses obtained in these groups were then compared with the responses produced by 100 μM histamine and 1 nM bradykinin in saline-pretreated groups, which served as control.

Results: Subthreshold doses of histamine elicited transient tachypnoeic, hyperventilatory, hypotensive, and bradycardiac responses, in rats pretreated with subthreshold doses of bradykinin [p < 0.01, two-sided Dunnett's test] but not in saline pretreated groups [p > 0.05, two-sided Dunnett's test]. Similar responses were elicited by bradykinin after histamine pretreatment compared to the saline-pretreated group. Furthermore, CVR responses produced by histamine in the bradykininpretreated group were greater in magnitude as compared to bradykinin-induced responses in the histamine-pretreated group [p < 0.05, two-sided Dunnett's test].

Conclusion: The present study demonstrates that both bradykinin and histamine potentiate one another in the elicitation of vasosensory reflex responses, and bradykinin is a better potentiator than histamine at the level of perivascular nociceptive afferents in producing reflex CVR changes.

Surgery, radiation, chemotherapy, and targeted therapy were the four basic kinds of cancer treatment until recently. Immuno-oncology (IO), or the concept that cancer cells were damaged by activating the body's immune system, has emerged and is explained as a unique and crucial method for treating different cancers over the last decade. The US Food and Drug Administration and the European Medicines Agency both approved this newly recognized way of treating cancer in 2020. Within IO, different therapeutic classes have arisen, which are the subject of this article. Immune checkpoint inhibitors are currently the most well-known therapeutic class of immuno-oncology medications due to their amazing ability to show efficacy in a variety of tumor types. Biomarkers were tested for different tumors like gastrointestinal cancer, whole Head, lower and upper part Neck cancer, and also cervical cancer by programmed death-ligand 1 (PD-L1) check point and their targets and are currently being utilized prior to treatment by using Pembrolizumab. However, the significance of PD-L1 expression for immune check point reticence therapy in other/different onco-cancer types remains unclear. Homogenized immuneoncology drugs with regular therapy have been recently studied and clinical efficacy outcomes have shown to be significantly improved. While IO agents are fast transforming the marketed treatment for cancer patients, there are still a number of obstacles to overcome in terms of associating their adverse effects and confirming those different healthcare systems, such as financing these expensive therapies. In addition to cancer vaccines and chimeric antigen receptor T-cell treatments, other IO drugs are in pipeline containing chimeric antigen receptor T-cell therapies; earlier ones have their own set of toxicities and high cost related challenges.

Aims: The aim of the study was to investigate the antihypertensive effect of L-Tartaric acid.

Background: L-Tartaric acid (L-TA) is a well-known weak organic acid that naturally occurs in a wide range of fruits, most notably in grapes, tamarind, and citrus.

Objective: The present study aimed to assess the effect of acute and subchronic administration of L-TA on blood pressure parameters in normotensive and hypertensive rats as well as its vasorelaxant potency.

Methods: In the current study, the antihypertensive activity of L-TA was pharmacologically studied. L-NAME-induced hypertensive and normotensive rats received L-TA (80 and 240 mg/kg) orally over six hours for the acute experiment and seven days for the subchronic treatment. Thereafter, systolic, diastolic, mean, mid arterial blood pressure, and pulse pressure as well as heart rate were evaluated. In the in vitro experiment, the vasorelaxant ability of L-TA was performed in ratisolated thoracic aorta.

Results: An important drop in blood pressure was recorded in L-NAME-induced hypertensives treated with L-TA. This molecule also produced a dose-dependent relaxation of the aorta precontracted with norepinephrine (NEP) and KCl. The study demonstrated that the vasorelaxant capacity of L-TA seems to be exerted through the activation of eNOS/NO/cGMP pathways.

Background & objective: The use of the hemoperfusion method is recommended for treating cytokine storms and reducing complications in patients with COVID-19. The side effects of this treatment are not known; therefore, this study was performed to determine the final outcome and complications of hemoperfusion in patients with COVID-19 hospitalized in ICU.

Methods: In this retrospective cross-sectional study, all patients with severe COVID-19 without any comorbidities or organ failure underwent hemoperfusion treatment in ICU at Kosar Hospital in Semnan, Iran, from March to November 2021 were included. The clinical data and short-term complications up to 10 days after hemoperfusion and the final outcome were extracted from medical files.

Results: The mean age of 40 patients with severe COVID-19 undergoing hemoperfusion was 57.5±15.9 years. Most (24, 60%) patients were male. The time interval from hospitalization to hemoperfusion and the time interval between hemoperfusion and final outcome was 4.85 days and 8.30 days, respectively. Arrhythmia, bleeding, thrombocytopenia, and coagulation disorders were the most common short-term complications of hemoperfusion in patients with COVID-19, respectively. Most complications occurred on the second and third days after hemoperfusion. Mortality occurred in 20 (50 %) patients with severe COVID-19 undergoing hemoperfusion in ICU.

Conclusion: It seems that the short-term complications and deaths due to hemoperfusion are relatively high in patients with COVID-19 admitted to the ICU. Further studies are recommended.

Obstructive hypertrophic cardiomyopathy results from asymmetric septal hypertrophy, which eventually obstructs the outflow of the left ventricle. Obstructive hypertrophic cardiomyopathy is linked to mutations in genes that encode for sarcomere proteins, including actin, β-myosin heavy chain, titin, and troponin. The mutations lead to structural abnormalities in myocytes and myofibrils, causing conduction irregularities and abnormal force generation. Obstructive hypertrophic cardiomyopathy is a chronic disease that worsens over time, and patients become at higher risk of developing atrial fibrillation, heart failure, and stroke. Up until recently, there were no disease- specific medications for obstructive hypertrophic cardiomyopathy. Nevertheless, the US Food and Drug Administration approved mavacamten on April 28, 2022, for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (New York Heart Association class II to III) in adults to improve functional capacity and symptoms. Its approval was based on data from EXPLORER- HCM and EXPLORER-LTE (NCT03723655). Mavacamten is a novel, first-in-class, orally active, allosteric inhibitor of cardiac myosin ATPase, which decreases the formation of actin- myosin cross-bridges, and thus, it reduces myocardial contractility, and it improves myocardial energetics. It represents a paradigm-shifting pharmacological treatment of obstructive hypertrophic cardiomyopathy. In this review, we describe its chemical and mechanistic aspects as well as its pharmacokinetics, adverse effects and warnings, potential drug-drug interactions, and contraindications.

Aims: The present work aimed to assess the antihypertensive activity of Salvia aucheri.

Background: Salvia aucheri (S. aucheri) is an aromatic and medicinal herb belonging to the Lamiaceae family. In Morocco, this plant is locally used for used to treat stomach, digestive disorders, rheumatism, and hypertension. Nevertheless, the effect of Salvia aucheri on hypertension has not yet been studied.

Objective: The objective of this investigation was to evaluate the beneficial effect of the aqueous extract of S. aucheri leaves on arterial blood pressure, systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) in normotensive and hypertensive rats. In addition, the effect of the aqueous extract of S. aucheri leaves on vasodilatation was assessed in isolated rat aortic rings with functional endothelium precontracted with epinephrine EP or KCl.

Methods: The aqueous extract of the aerial parts of S. aucheri (AESA) was obtained, and its antihypertensive ability was pharmacologically investigated in L-NAME hypertensive and normotensive rats. The rats received AESA orally at two selected doses of 100 and 140 mg/kg for six hours (acute experiment) and seven days (sub-chronic). Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. Moreover, the vasorelaxant activity of AESA was performed in thoracic aortic ring rats. In addition, the mechanisms of action involved in the vasorelaxant effect were studied.

Results: The results indicated that AESA significantly reduced the systolic, diastolic, and mean arterial blood pressure in hypertensive rats over both single and repeated oral administration. However, AESA did not change the blood pressure parameters in normotensive rats. Concerning the results of vasorelaxant activity, the results showed that AESA was able to provoke potent vasorelaxant ability, which seems to be mediated through direct nitric oxide (NO) and NO-cyclic guanosine monophosphate pathways.

Conclusion: The study elucidates the beneficial action of AESA as an antihypertensive and vasorelaxant agent.