RESUMO
Because of evident role of renin-angiotensin system in the etiology of rheumatoid arthritis, the current study's objective was to assess the anti-arthritic efficacy of ramipril through CFA-instigated arthritic model. The drug has been shown to have anti-inflammatory potential. CFA-instigated arthritic model assessed the anti-arthritic efficacy of ramipril by estimating different parameters, including paw volume, arthritic index scoring, haematological and biochemical attributes, histological and radiographic analyses, and various cytokines level. Ramipril significantly (p < 0.001) reduced paw volume and the arthritic index especially at the dose of 4mg/kg. The biochemical and haematological changes were likewise restored to normal by ramipril administration with an increase in anti-inflammatory cytokines while reducing pro-inflammatory cytokines level. Ramipril's ability to prevent arthritis by preserving the normal architecture of arthritis-induced joints is further supported by radiographic and histological investigation. The study's findings demonstrated ramipril's considerable anti-arthritic activity. To identify the precise mechanism of action, however, thorough mechanistic studies are still needed.
Assuntos
Artrite Experimental , Ramipril , Ratos , Animais , Adjuvante de Freund , Ramipril/efeitos adversos , Extratos Vegetais/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Anti-Inflamatórios/uso terapêutico , CitocinasRESUMO
For most researchers, discovering new anticancer drugs to avoid the adverse effects of current ones, to improve therapeutic benefits and to reduce resistance is essential. Because the COX-2 enzyme plays an important role in various types of cancer leading to malignancy enhancement, inhibition of apoptosis, and tumor-cell metastasis, an indispensable objective is to design new scaffolds or drugs that possess combined action or dual effect, such as kinase and COX-2 inhibition. The start compounds A1 to A6 were prepared through the diazo coupling of 3-aminoacetophenone with a corresponding phenol and then condensed with two new chalcone series, C7-18. The newly synthesized compounds were assessed against both COX-2 and epidermal growth factor receptor (EGFR) for their inhibitory effect. All novel compounds were screened for cytotoxicity against five cancer cell lines. Compounds C9 and G10 exhibited potent EGFR inhibition with IC50 values of 0.8 and 1.1 µM, respectively. Additionally, they also displayed great COX-2 inhibition with IC50 values of 1.27 and 1.88 µM, respectively. Furthermore, the target compounds were assessed for their cytotoxicity against pancreatic ductal cancer (Panc-1), lung cancer (H-460), human colon cancer (HT-29), human malignant melanoma (A375) and pancreatic cancer (PaCa-2) cell lines. Interestingly, compounds C10 and G12 exhibited the strongest cytotoxic effect against PaCa-2 with average IC50 values of 0.9 and 0.8 µM, respectively. To understand the possible binding modes of the compounds under investigation with the receptor cites of EGFR and COX-2, a virtual docking study was conducted.
Assuntos
Antineoplásicos , Chalconas , Inibidores de Ciclo-Oxigenase 2 , Proteínas de Neoplasias , Neoplasias , Inibidores de Proteínas Quinases , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Chalconas/síntese química , Chalconas/química , Chalconas/farmacologia , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Humanos , Estrutura Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologiaRESUMO
Osteogenic sarcoma is the central malignant bone neoplasm affecting the bones of arms and legs and rarely the soft tissues outside the bones. Historically, amputation was the chief surgical technique; currently, the popular standard is limb salvage surgery (LSS), although both procedures' effect on 5-year-event survival, 5-year disease-free survival rates (DFS) and the local recurrence is uncertain. Therefore, this meta-study aimed to establish the relationship between the effect of LSS and amputation in subjects with osteogenic carcinoma. A systematic survey till January 2021 to know the effect of LLS vs amputation with subjects treated with neoadjuvant chemotherapy was conducted. Clinical studies were identified with 9760 subjects with osteosarcoma of the extremities at the beginning of the trial; 7095 of them were managed with limb salvage surgery and 2611 with amputation. This study tried to compare the effects of LSS vs amputation in subjects with osteogenic sarcoma in the extremities. The dichotomous method in statistical analysis was used as a tool for establishing odds ratio (OR) at a confidence interval of 95% (CI) to assess the efficiency of LSS and amputees with osteosarcoma of the extremities with a fixed or random-effect model. Although patients with osteosarcoma of the extremities managed with LSS were significantly related to a higher local recurrence rate than those treated with amputation, they were also associated with higher 5-year overall survival (OS) than amputation. Patients showed no significant difference in a 5-year DFS rate between LSS vs amputation. The subjects who have undergone LSS for osteosarcoma of the extremities may have a higher risk of local recurrence than amputees. However, LSS may increase 5-year OS compared to amputees. These results depict that local recurrence of osteosarcoma does not influence survival rate. However, more studies are needed to validate this finding.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Salvamento de Membro/métodos , Terapia Neoadjuvante , Osteossarcoma/tratamento farmacológico , Osteossarcoma/cirurgia , Osteossarcoma/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Amputação Cirúrgica/métodos , Extremidades/cirurgia , Recidiva Local de Neoplasia/cirurgiaRESUMO
A meta-analysis was performed to assess the effect of surgical site wound infections and risk factors in neonates undergoing surgery. A systematic literature search up to January 2022 incorporated 17 trials involving 645 neonates who underwent surgery at the beginning of the trial; 198 of them had surgical site wound infections, and 447 were control for neonates. The statistical tools like the dichotomous or continuous method used within a random or fixed-influence model to establish the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to evaluate the risk factors and influence of surgical site wound infections in neonates undergoing surgery. Surgical site wound infections had significantly higher mortality with OR value 2.03 at 95% CI 1.40-2.95 with P-value <0.001, the longer length of hospital stay (MD, 31.88; 95% CI, 18.17-45.59, P < 0.001), and lower birthweight of neonates (MD, -0.30; 95% CI, -0.53 to -0.07, P = 0.01) compared with neonates with no surgical site wound infections undergoing surgery. However, no remarkable change was observed with surgical site wound infections in the gestational age at birth of neonates (MD, -0.70; 95% CI, -1.46 to 0.05, P = 0.07), and the preoperative antibiotic prophylaxis (OR, 1.28; 95% CI, 0.57-2.87, P = 0.55) compared with no surgical site wound infections for neonates undergoing surgery. Surgical site wound infections had significantly higher mortality, a longer length of hospital stay, and lower birthweight of neonates. However, they had no statistically significant difference in the gestational age at birth of neonates and the preoperative antibiotic prophylaxis compared with no surgical site wound infections for neonates undergoing surgery. Furthermore, evidence is needed to confirm the outcomes.
Assuntos
Antibioticoprofilaxia , Infecção da Ferida Cirúrgica , Recém-Nascido , Humanos , Peso ao Nascer , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Fatores de Risco , Tempo de InternaçãoRESUMO
Background: Individuals with underlying chronic illnesses have demonstrated considerable hesitancy towards COVID-19 vaccines. These concerns are primarily attributed to their concerns over the safety profile. Real-world data on the safety profile among COVID-19 vaccinees with comorbid conditions are scarce. This study aimed to ascertain the side-effects profile after two doses of COVID-19 vaccines among chronic-disease patients. Methodology: A cross-sectional questionnaire-based study was conducted among faculty members with comorbid conditions at a public educational institute in Saudi Arabia. A 20-item questionnaire recorded the demographics and side effects after the two doses of COVID-19 vaccines. The frequency of side effects was recorded following each dose of vaccine, and the association of the side-effects score with the demographics was ascertained through appropriate statistics. Results: A total of 204 patients with at least one comorbid condition were included in this study. A total of 24 side effects were reported after the first dose and 22 after second dose of the COVID-19 vaccine. The incidence of at least one side effect was 88.7% and 95.1% after the first and second doses of the vaccine, respectively. The frequent side effects after the first dose were pain at the injection site (63.2%), fatigue (58.8%), fever (47.5%), muscle and joint pain (38.7%), and headache (36.3%). However, pain at the injection site (71.1%), muscle and joint pain (62.7%), headache (49.5%), fever (45.6%), and stress (33.3%) were frequent after the second dose. The average side-effects score was 4.41 ± 4.18 (median: 3, IQR: 1, 6) and 4.79 ± 3.54 (median 4, IQR: 2, 6) after the first and second dose, respectively. Female gender, diabetes mellitus, hypertension, hyperlipidemia, comorbidity > 2, family history of COVID-19, and the AstraZeneca vaccine were significantly associated with higher side-effect scores. Only 35.8% of study participants were satisfied with the safety of COVID-19 vaccines. Conclusions: Our analysis showed a high proportion of transient and short-lived side effects of Pfizer and AstraZeneca vaccines among individuals with chronic illnesses. However, the side-effects profile was comparable with the safety reports of phase 3 clinical trials of these vaccines. The frequency of side effects was found to be associated with certain demographics, necessitating the need for further investigations to establish a causal relationship. The current study's findings will help instill confidence in the COVID-19 vaccines among people living with chronic conditions, overcome vaccine hesitancy, and increase vaccine coverage in this population.
Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Feminino , Vacinas contra COVID-19/efeitos adversos , Arábia Saudita/epidemiologia , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Comorbidade , Dor , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , ArtralgiaRESUMO
The resurgence of scrutiny in plant-based medicine is mainly due to the current widespread belief that "green medicine" is safe and more dependable than the expensive synthetic drugs. The current study was focused to evaluate the anti-myocardial ischemic potential of Berberis orthobotrys Bien ex Aitch against chemically induced myocardial ischemia in animal models. Myocardial ischemia was instigated in Sprague Dawley rats of either sex (250-450g) by administration of Isoproterenol (ISO) and doxorubicin (DOX) at doses of 25mg/kg b.w and 15mg/kg b.w. respectively. The protective effect of the plant extract was explored by pretreating a group of animals with aqueous methanolic extract of Berberis orthobotrys roots at a dose of 50mg/kg b.w. (orally) for 10 days in ISO-ischemic model while for doxorubicin ischemic model; the study was conducted for 14 days. The findings of the study revealed that serum levels of cardiac marker enzymes were significantly increased (p<0.0001) followed by the administration of Isoproterenol and doxorubicin whereas the pretreatment with aqueous methanolic plant extract had significantly (p<0.0001) prevented the rise in the same, as compared to both intoxicated groups. The statistical analysis of the study led to the conclusion that Berberis orthobotrys possesses cardio protective potential against chemically induced myocardial ischemia.
Assuntos
Doxorrubicina/toxicidade , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Berberis , Isoproterenol/toxicidade , Extratos Vegetais/química , Ratos , Ratos Sprague-DawleyRESUMO
Terbutaline have been reported to have anti-inflammatory activity. Present study aimed to check the anti-arthritic activity of terbutaline. The drug was tested using in vitro models (bovine serum albumin denaturation, egg albumin denaturation and HRBC membrane stabilization) and in vivo (formaldehyde induced arthritis). Results of bovine serum albumin denaturation assay illustrated that terbutaline inhibited 89.54±0.46% denaturation at 6400µg/ml concentration. Terbutaline resulted in dose dependent impediment of protein denaturation in egg albumin denaturation assay with 74.40±0.72% inhibition at concentration of 6400µg/ml. Terbutaline also showed protection of HRBC membrane against hypotonic stress in a dose dependent manner, with maximum 76.45±0.62% prevention at 6400µg/ml concentration. Results of formaldehyde induced arthritis model showed that paw volume was significantly declined by terbutaline with maximum percentage inhibition at 10th day of study period which implies immune inhibitory potential of terbutaline. Findings of present study concluded that terbutaline has arthritis reducing potential possible through inhibitory effects on synthesis and release of inflammatory mediators as well as limiting the formation of autoantigen. Thus, terbutaline might be the potential candidate for use in treatment of arthritis.
Assuntos
Artrite Experimental/prevenção & controle , Simpatomiméticos/farmacologia , Terbutalina/farmacologia , Animais , Artrite Experimental/induzido quimicamente , Feminino , Formaldeído/toxicidade , Masculino , Ovalbumina/química , Ratos , Ratos Sprague-Dawley , Soroalbumina BovinaRESUMO
In developing countries, myocardial ischemia and the resulting impairments in heart function are the leading cause of illness and mortality. Thymus linearis Benth has been used as an antibiotic, antioxidant, and antihypertensive agent for centuries. The goal of this investigation was to see if Thymus linearis could protect isoproterenol and doxorubicin-induced myocardial ischemia in vivo at doses of 25 mg/kg s.c. and 15 mg/kg i.p., respectively. The level of cardiac enzymes (CK-MB, LDH, and AST) in the serum isolated from the experimental animal's blood was used to determine myocardial ischemia. The anti-ischemic potential was assessed by comparing the levels of the aforementioned cardiac biomarkers in the intoxicated and treated animal groups. The study found substantial increase (p0.0001) in the serum levels of CK-MB, LDH, AST when compared to intoxicated groups, while pretreatment of animals with crude extract of Thymus linearis significantly reduced the rise in serum cardiac indicators. The findings of the study indicated that the aqueous methanolic Thymus linearis crude extract has cardioprotective potential against Isoproterenol and Doxorubicin-induced cardiac necrosis in rats.
Assuntos
Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/prevenção & controle , Extratos Vegetais/farmacologia , Thymus (Planta)/química , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Feminino , Isoproterenol/toxicidade , L-Lactato Desidrogenase/sangue , Masculino , Extratos Vegetais/química , Ratos , Ratos Sprague-DawleyRESUMO
Ciprofloxacin is a commonly used antibiotic for treatment of bacterial conjunctivitis. The conventional eye drop dosage form is the widely used mode of treatment, but it has low corneal residence time. This drawback can be overcome by developing a bioadhesive noisome system (chitosan-coated) for enhanced corneal residence time. The niosomes were prepared by thin-film hydration technique and optimized by using Box-Behnken statistical design software. Cholesterol (A), Span 60 (B), and sonication time (C) were selected as independent variables, whereas vesicle size (Y1 in nm), entrapment efficiency (Y2 in %), and drug release (Y3 in %) were chosen as dependent variables. The vesicle size, entrapment efficiency, and drug release of optimized CIP niosomes (CIP-NSMopt) were found to be 180.34 ± 5.13 nm, 78.32 ± 4.49%, and 82.87 ± 4.01% (in 12 h), respectively. Further CIP-NSMopt was coated with different chitosan concentrations (0.1 to 0.3%) to enhance mucoadhesion. Finally, optimized chitosan-coated niosomes (chitosomes; CIP-CHTopt) showed a vesicle size of 210.65 ± 2.76 nm, zeta potential of - 35.17 ± 2.25Mv, and PDI of 0.221. CIP-CHTopt exhibited sustained release profile (75.31% in 12 h) with the Korsmeyer-Peppas kinetic model (R2 = 0.980). The permeation study showed 1.79-fold enhancements in corneal permeation compared with marketed CIP eye drop. The hen's egg chorioallantoic membrane (HET-CAM) study showed 0 scores (no irritation), and it was further confirmed by corneal hydration and histopathology study. The antimicrobial study exhibited a significant high zone (P < 0.05) of inhibition against tested organism. Our findings demonstrated that chitosan-coated niosomes are a promising drug carrier to enhance corneal contact time and treatment of bacterial conjunctivitis.
Assuntos
Antibacterianos/química , Quitosana/química , Membrana Corioalantoide/efeitos dos fármacos , Ciprofloxacina/química , Soluções Oftálmicas/química , Animais , Galinhas , Ciprofloxacina/farmacologia , Ciprofloxacina/toxicidade , Portadores de Fármacos , Composição de Medicamentos , Lipossomos/químicaRESUMO
OBJECTIVE: Researchers have confirmed that chronic administration of drugs at high doses causes genotoxicity which serve as first step in development of cancers. Apremilast, a phosphodiesterase-4 inhibitor is Food and Drug Administration (FDA) approved drug for Psoriatic Arthritis. The present study designed to conduct genotoxicity testing using the genotoxic study which give simple, sensitive, economical and fast tools for the assessment of damage of genetic material. METHODS: To conduct genotoxicity study of Apremilast, 60 Swiss albino male mice divided into 6 groups (n = 10). Group1 served as a normal control group without any treatment, Group 2 treated as a disease control and administered with cyclophosphamide 40 mg/kg, IP. Group 3, 4, 5 and 6 treated as test groups and received 10, 20, 40 and 80 mg/kg/day Apremilast respectively. The total duration of study was 13 weeks. At termination day animals were sacrificed and chromosomal aberration assay (BMCAA) and micronucleus assay (BMMNA) were performed to know the genotoxicity potential of Apremilast. RESULTS: The results indicates significant rise in chromosomal aberrations (CA) frequency in bone marrow cells and decrease in the MI of the disease control animals as well as Apremilast treated groups. Further significant (p < 0.001; p < 0.0001) increase in score of micronucleated polychromatic erythrocytes (MNPCEs) and percentage of micronucleated PCEs per 1000 PCEs and decrease in the ratio of polychromatic/normochromatic erythrocytes (PCE/NCE) was observed in micronucleus assay. Genotoxic effect increases with the increase of Apremilast dose. Conclusion: Finding of present indicates that Apremilast shows genotoxic potential on high administration although further detailed toxicity studies required for confirmations.
RESUMO
The aim of this study was the evaluation of diuretic potential of Delphinium brunonianum. Acute diuretic effect in rats was evaluated 8 h after administration of various doses of crude extract, fractions and hydrochlorthiazide. While, prolonged effect of butanolic fraction was assessed after 7days of oral administration in rats. Thereafter, involvement of different pathways in diuretic activity was also appraised. Furthermore, polyphenolic contents in butanolic fraction were assessed using HPLC/UV-VIS technique. All doses of extract and fractions induced a prominent increase in urine and Na+ excretion with no effect on excretion of K+. Prior administration of indomethacin and atropine considerably avoided the diuretic effect of butanolic fraction. Regarding the quantitative chemical analysis the polyphenolic contents were recorded as 28.78 µg/mg. Thus results of present investigation suggested that Delphinium brunonianum possess remarkable diuretic potential.
Assuntos
Delphinium/química , Diuréticos/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Atropina/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Indometacina/farmacologia , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Sódio/metabolismoRESUMO
Ranunculus scleratus Linn. is used in folk medicine to treat hypertension. This study was aimed at providing validation to its traditional use and to explore underlying mechanisms of action. Effects of hydro-ethanolic crude extract of the plant and its fractions on blood pressure was evaluated using direct surgical method in normotensive and in fructose induced hypertensive rats. Various doses of crude extract, RSC, (5, 10, 20, 30mg/kg) and all fractions (3, 5, 10, 20mg/kg) were studied. Results suggested that aqueous fraction of R. scleratus (RSA) produced most pronounced effects at 10mg/kg in normotensive and at 20mg/kg in hypertensive animals. Underlying mechanisms, using various pharmacological antagonists were also elucidated. Results suggested the involvement of muscarinic receptor, angiotensin converting enzyme (ACE) inhibition, ganglionic block and nitric oxide (NO) release in presenting hypotensive response.
Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Extratos Vegetais/farmacologia , Ranunculus , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/isolamento & purificação , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Frutose , Bloqueadores Ganglionares/isolamento & purificação , Bloqueadores Ganglionares/farmacologia , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Antagonistas Muscarínicos/isolamento & purificação , Antagonistas Muscarínicos/farmacologia , Óxido Nítrico/metabolismo , Extratos Vegetais/isolamento & purificação , Ranunculus/química , Ratos Sprague-Dawley , Receptores Muscarínicos/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
Acacia jacquemontii Benth. is used traditionally to treat hypertension but no scientific literature supports this claim. So, this study was aimed at validating this claim. This was done by injecting various doses of crude extract of Acacia jacquemontii, AJC (5, 10, 20, 30mg/kg) and all fractions (hexane, ethyl acetate, n-butanol and aqueous) (3, 5, 10, 20mg/kg) intravenously in anaesthetized rat. Based on the results, butanol fraction (AJB) at 20mg/kg was found to be the most potent, so it was selected for exploring mechanisms of action. For this purpose, different groups were injected with various pharmacological inhibitors (L-NAME, atropine, captopril, propranolol and hexamethonium) prior to AJB administration. Also, AJB at 20mg/kg was evaluated for prolonged hypotensive effect for the period of 40 min. Results showed a significant dose dependent reduction in BP in normotensive and in hypertensive rats. AJC and AJB produced a decline in SBP, DBP and MAP with p<0.05 - p<0.001 and p<0.001 respectively in normotensive animals. Whereas in hypertensive animals, AJC showed significant reduction at 5mg/kg with p<0.01 and at 10, 20 and 30 mg/kg with p<0.001. AJB produced a decline in hypertensive animals at all tested doses with p<0.001. AJB resulted in hypotensive effect mediated by ß receptors, ganglionic block operating central sympathetic neural responses and renin angiotensin aldosterone system (RAAS). This study supports the ethnomedicinal claim of Acacia jacquemontii Benth. in treating hypertension.
Assuntos
Acacia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Extratos Vegetais/farmacologia , Acacia/química , Animais , Anti-Hipertensivos/isolamento & purificação , Modelos Animais de Doenças , Etnofarmacologia , Frutose , Gânglios Autônomos/efeitos dos fármacos , Gânglios Autônomos/fisiopatologia , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Extratos Vegetais/isolamento & purificação , Ratos Sprague-Dawley , Receptores Adrenérgicos beta/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologiaRESUMO
Sorghum halepense L (Poaceae), ordinarily it is known as Johnson grass and locally as baru. This study was designed to find the vascular mechanisms underlying the hypotensive activity of S. halepense. In this study, effect of S. halepense seed extract/fractions on various blood pressure parameters were evaluated in normal and fructose induced hypertensive rats by invasive technique. Possible underlying hypotensive mechanism of active fraction was determined by using various pharmacological inhibitors. S. halepense extract/fractions vasorelaxant effect were also evaluated on rat aorta rings in organ bath and various intracellular signaling pathway inhibitors were used for determination of underlying mechanisms. S. halepense extract/fractions produced blood pressure lowering effect with most significant effect by its aqueous soluble fraction at dose of 10mg/kg. This effect was attenuated by pretreatment of atropine. Aqueous soluble fraction produced endothelium dependent vasorelaxation in rat aortic rings that was inhibited by pretreatment of atropine after phenylephrine induced contraction. The vasorelaxant effect of aqueous soluble fraction was attenuated by potassium channel blockers and also produced inhibitory effect on calcium entry through calcium channels. It also suppressed phenylephrine induced contraction like verapamil. By HPLC analysis found vanillic acid and naringinin in it. In conclusion, aqueous soluble fraction of S.halepense possess phytoconstituents which may be responsible for hypotensive and vasorelaxant effect of Sorghum halepense.
Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Extratos Vegetais/farmacologia , Sorghum , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Anti-Hipertensivos/isolamento & purificação , Modelos Animais de Doenças , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Frutose , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Extratos Vegetais/isolamento & purificação , Ratos Sprague-Dawley , Sorghum/química , Ácido Vanílico/isolamento & purificação , Ácido Vanílico/farmacologia , Vasodilatadores/isolamento & purificaçãoRESUMO
Teucrium stocksianum Boiss. is an aromatic perennial herb. It has long been used traditionally in the treatment of hypertension in northern areas of Pakistan. The aim of this study was to evaluate its folkloric claim as hypotensive plant, phytochemical analysis and to predict potential phytoconstituent through in-silico studies. Hypotensive effect was investigated in anesthetized normotensive Sprague-Dawley rats. Recording of chronotropic and inotropic effect of plant extract in isolated right atria was done using tissue organ bath technique. Further, phytochemical characterization was performed through LC-MS. Whereas docking studies were carried out against M2 mAchR and Ca2+ Channel receptor. Dose dependent reduction in systolic, diastolic, mean arterial pressure and heart rate was observed. Pretreatment with atropine and amlodipine significantly (p<0.001) reduced the hypotensive and negative chronotropic and inotropic effect. Phytochemical studies revealed the presence of twenty active compounds including Luteolin, Sarmentosin epoxide and Quinic acid. Docking studies showed pronounced interactions of majority of these phytochemicals with M2 mAch receptor in agonistic way and Ca2+ Channel receptor in antagonistic way. Results speculate that dose dependent hypotensive and bradycardia effect of Teucrium stocksianum are mediated through muscarinic pathway and Ca2+antagonism and is also well predicted by in-silico studies.
Assuntos
Anti-Hipertensivos/farmacologia , Compostos Fitoquímicos/análise , Extratos Vegetais/farmacologia , Teucrium/química , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/química , Ratos , Ratos Sprague-Dawley , Receptor Muscarínico M2/antagonistas & inibidoresAssuntos
COVID-19 , Reposicionamento de Medicamentos , Antivirais/uso terapêutico , Humanos , SARS-CoV-2RESUMO
OBJECTIVE: Self-medication has become a major concern among nonmedical professionals during the treatment of COVID-19. Such concerns have been attributed to the adverse effect of information shared via media outlets. Here, a survey was undertaken among nonhealthcare professionals to find out the adverse effect of media on self-medication for treating COVID-19. METHODS: A questionnaire-based survey was conducted electronically among nonmedical professionals (270 respondents). The questionnaire comprised three main components: demographic, education, and factor for self-medication. Statistical analysis of the data was made using analysis of variance to determine the degree of agreement between the response of participants with education below and above graduation. RESULTS AND CONCLUSION: Most of the respondents agreed that they get information about the COVID-19 medicines from different media. However, most of them do not visit the reliable source like World Health Organization (WHO) website to get information about COVID-19. The respondents were aware of the usage of medications such as Remdesvir, azithromycin, vitamins, herbal preparations, paracetamol, and cetirizine for COVID-19. The usage of herbal preparation may be due to their promotion in the media as over the counter drugs (OTC) products. It has been proposed to create more awareness and warning signs for the patients in and around pharmacy and hospital. Media campaign to create awareness for the prevention of COVID-19 spread should also be added with a caution line not to use any medication for treatment without prior consultation with physician. The matter of concern is that only a small fraction of the respondents follow WHO website to get information regarding COVID-19, which mandates to create awareness among the public regarding the role of WHO in healthcare. A significant agreement was noted between below graduates and post-graduates regarding questions such as visiting WHO website and the safety of taking medicine without consulting physician. Media is a contributing factor to self-medication, and measures of caution are highly imperative.
Assuntos
COVID-19 , Humanos , Automedicação , Medicamentos sem Prescrição/efeitos adversos , Escolaridade , Inquéritos e QuestionáriosRESUMO
Myocardial infarction (MI) is a cardiovascular disease that occurs due to the blockage of the coronary artery. Subsequently, cardiac muscles receive a lower oxygen supply, which leads to the death of cardiac muscles. The etiology of MI is linked to various environmental, occupational, and genetic factors. Various studies have been conducted on the polymorphism of genes involved in MI. Previous studies have shown that different variants of the methylene tetrahydrofolate reductase (MTHFR) gene are involved in causing MI by altering the metabolism of folate and homocysteine. However, the genetic polymorphism of MTHFR C677T (rs1801133) and its association with MI in the presence of diabetes mellitus (DM) as a risk factor still needs to be investigated. This study recruited 300 participants who were divided into three groups, i.e., the control, MI, and MI-DM. The blood samples collected from the study participants were subjected to various biochemical tests and their clinical parameters were monitored. MTHFR C677T (rs1801133) genotyping was performed by Tetra ARMS PCR using predetermined primers. The MTHFR C677T (rs1801133) polymorphism was associated with MI in the presence of DM as a risk factor among the participants. The MTHFR C677T (rs1801133) T/T homozygous genotype was found to be significant among MI patients in the presence of DM as a risk factor.
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BACKGROUND: Diversifying the conventional role of community pharmacists from dispensing to involvement in public health services could help in optimized patient care and ultimately good health practices. The current study aimed to ascertain the involvement of community pharmacists, barriers to involvement, their preparedness towards the provision of public health services in the future, and effective strategies to improve their existing role, especially in remote areas of the Kingdom of Saudi Arabia. METHODS: A cross-sectional study was conducted in the Al-Jouf region of Saudi Arabia (KSA), between January to April 2023. A convenient sampling technique was used to recruit community pharmacists (CPs). A self-designed and validated questionnaire was used for data collection. The relative importance index (RII) was utilized to rank the barriers to participation in public health services. Data were subjected to statistical analysis using SPSS. RESULTS: This study recruited 119 participants (mean age: 32.2 ± 7.9; male gender: 67.2%). Of these, 91.6% were involved in the provision of public health services at community pharmacies. Majority of CPs (n = 114/119, 95.8%) provided drug use-related written information to the patients, and the least practiced service was screening of dyslipidemia (n = 81; 68.1%). According to RII, the major barrier was the lack of time given by patients (RII: 0.812). Overall, the majority of the pharmacists (n = 94/119; 79%) were willing to provide public health services. Most of the CPs reported that empowerment through education and awareness (n = 100/119; 84%) is most effective strategy to enhance the involvement of pharmacists in public health services. CONCLUSIONS: Findings of the present study underscored the adequate participation of community pharmacists in public health activities. Further studies are required in other remote regions of KSA to get a clear insight into the overall participation of community pharmacists in public health services and generalize the findings.
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Background and purpose: The study focuses on examining the relationship between a single nucleotide polymorphism (SNP) in KLF14 rs4731702 and risk of type 2 diabetes mellitus (T2DM) and dyslipidemia in different ethnic populations. The purpose of this study was to evaluate the association between KLF14 rs4731702 and serum lipid profile and to determine the frequency distribution of KLF14 rs4731702 among T2DM and cardiometabolic patients. Methods: A total of 300 volunteers were recruited, consisting of three groups: 100 healthy individuals, 100 individuals diagnosed with T2DM, and 100 individuals diagnosed with cardiometabolic disorders. Biochemical analysis of blood samples was conducted to assess various biomarkers related to glycemic control and lipid profile. This involved measuring levels of glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and ApoA1. Genotyping analysis was performed to investigate KLF14 rs4731702 polymorphism. The Tetra ARMS-PCR method was employed for genotyping analysis. Results: The results of biochemical profiling revealed a significant association between altered glycemic biomarkers and lipid profile in diseased patients compared to healthy participants. The frequencies of KLF14 rs4731702 alleles and genotypes were compared between the control group and T2DM group. A statistically significant difference was observed, indicating a potential association between KLF14 rs4731702 and T2DM. In the dominant inheritance model of KLF14 rs4731702 SNP, a statistically significant difference [odds ratio (95% confidence interval)] of 0.56 (0.34 -0.96) was found between the control and T2DM subjects. This suggests that the presence of certain genotypes influences the risk of T2DM. In T2DM patients, individuals carrying the C allele exhibited compromised insulin sensitivity, decreased HDL-C and ApoA1 levels, and increased serum glucose, TG, and LDL-C concentrations. Conversely, TT genotype carriers demonstrated increased levels of HDL-C and ApoA1, lower insulin resistance, serum glucose, LDL-C, and TG levels. Conclusion: The study's findings indicate that dyslipidemia in T2DM patients is associated with reduced KLF14 functionality due to CC and CT genotypes, leading to insulin resistance and an increased risk of cardiovascular diseases. Additionally, risk of KLF14 rs4731702 polymorphism was found to increase with age and was more prevalent in female than in male individuals. These insights contribute to understanding genetic factors influencing the development and progression of T2DM and dyslipidemia in different ethnic populations.