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A Review on the Pharmacological Importance of PDE5 and Its Inhibition to Manage Biomedical Conditions PDE5的药理意义及其对生物医学疾病的抑制作用综述
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-09-01 DOI: 10.1177/0976500X221129008
Queen Saikia, A. Hazarika, Ritu Mishra
Phosphodiesterase type 5 (PDE5) is a cyclic GMP (cGMP) specific protein. It hydrolyzes the phosphodiesterase linkage and catalyzes the conversion of cGMP to 5’ GMP, which controls different physiological activities of the body. PDE5 is associated with biomedical conditions like neurological disorders, pulmonary arterial hypertension, cardiomyopathy, cancer, erectile dysfunction, and lower urinary tract syndrome. Inhibition of PDE5 has now been proven pharmaceutically effective in a variety of therapeutic conditions. Avanafil, tadalafil, sildenafil, and vardenafil are the most commonly used PDE5 inhibitors (PDE5i) today which are often used for the management of erectile dysfunction, lower urinary tract syndromes, malignancy, and pulmonary arterial hypertension. However, these synthetic PDE5i come with a slew of negative effects. Some of the most common side effects include mild headaches, flushing, dyspepsia, altered color vision, back discomfort, priapism, melanoma, hypotension and dizziness, non-arteritic anterior ischemic optic neuropathy (NAION), and hearing loss. In light of the potential negative effects of this class of medications, there is a lot of room for new, selective PDE5 inhibitors to be discovered. We have found 25 plant botanical compounds effectively inhibiting PDE5 which might be useful in treating a variety of disorders with minimal or no adverse effects.
磷酸二酯酶5 (PDE5)是一种环GMP (cGMP)特异性蛋白。它水解磷酸二酯酶链,催化cGMP转化为5′GMP,控制机体的各种生理活动。PDE5与神经系统疾病、肺动脉高压、心肌病、癌症、勃起功能障碍和下尿路综合征等生物医学疾病有关。抑制PDE5现已被证明在多种治疗条件下具有药学上的有效性。阿那非、他达拉非、西地那非和伐地那非是目前最常用的PDE5抑制剂(PDE5i),常用于治疗勃起功能障碍、下尿路综合征、恶性肿瘤和肺动脉高压。然而,这些合成的PDE5i带来了一系列的负面影响。一些最常见的副作用包括轻度头痛、潮红、消化不良、色觉改变、背部不适、阴茎勃起、黑色素瘤、低血压和头晕、非动脉性前缺血性视神经病变(NAION)和听力损失。鉴于这类药物的潜在负面影响,有很大的空间来发现新的,选择性PDE5抑制剂。我们已经发现了25种有效抑制PDE5的植物化合物,这些化合物可能对治疗各种疾病有用,而且副作用很小或没有副作用。
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引用次数: 2
A Comparative Study of Chromium: Therapeutic Uses and Toxicological Effects on Human Health 铬的比较研究:治疗用途和对人体健康的毒理学影响
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-09-01 DOI: 10.1177/0976500X221128646
Anaiska Ray, J. Jankar
Chromium is an essential trace element whose deficiency can cause impairment of glucose tolerance, growth and various biological functions. There are two isotopes of chromium-trivalent chromium and hexavalent chromium. Both the isotopes of chromium have quite different effects on the human body. The objective of this narrative review is to compile the different effects of the two isotopes of chromium and give a comprehensive analysis of the effects of hexavalent and trivalent chromium. Data from various studies across different forums were compared to provide a concrete analysis of the therapeutic and harmful effects of two isotopes of chromium on human health. Chromium plays a vital role in the biological functions of the body. It might be helpful in balancing the glycaemic levels, triglyceride levels and cholesterol levels in the body. Excessive intake of chromium is harmful for health. Overexposure to chromium can lead to carcinogenic effects. Consumption of an insufficient amount of chromium might not be adequate as well. Trivalent chromium can be quite beneficial if taken in proper quantities. Hexavalent chromium can cause cancer. Trivalent chromium is beneficial, while hexavalent chromium is harmful to human health.
铬是人体必需的微量元素,缺乏铬可引起糖耐量、生长和各种生物功能的损害。铬有两种同位素——三价铬和六价铬。铬的两种同位素对人体的影响大不相同。这篇叙述性综述的目的是汇编两种铬同位素的不同影响,并对六价和三价铬的影响进行综合分析。对来自不同论坛的各种研究的数据进行了比较,以便对铬的两种同位素对人体健康的治疗和有害影响进行具体分析。铬在人体的生物功能中起着至关重要的作用。它可能有助于平衡体内的血糖水平、甘油三酯水平和胆固醇水平。过量摄入铬对健康有害。过量接触铬会导致致癌作用。摄入不足的铬也可能是不够的。如果摄入适量,三价铬是非常有益的。六价铬会致癌。三价铬对人体有益,而六价铬对人体有害。
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引用次数: 2
Homocysteine Levels and Clinical Outcomes in Schizophrenia—A Pilot Randomized Controlled Trial 精神分裂症患者同型半胱氨酸水平与临床疗效的初步随机对照试验
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-09-01 DOI: 10.1177/0976500X221128649
Venkata Aksheena Varahi Vedam, M. Ghanta, S. Kantipudi, D. David, Melanathuru Vijayalakshmi, Poojith Nuthalapati
Objectives: To find out the relation between homocysteine levels in peripheral blood and the effectiveness as well as the safety of haloperidol and olanzapine in schizophrenia treatment. Materials and Methods: A prospective randomized parallel-group open-label interventional clinical trial was conducted on 40 mild to moderate schizophrenia patients. To compare the efficacy of olanzapine and haloperidol Brief Psychiatric Rating Scale (BPRS) score was used. Homocysteine levels of peripheral blood and Abnormal Involuntary Movement Scale scores were evaluated. Results: BPRS score improved in both groups on day 14 and day 28. But significantly more with olanzapine (P value =.001). The olanzapine group showed a higher reduction (13.91±0.47 to 9.74±0.5) in homocysteine levels than the haloperidol group. Also, the BPRS scores negatively correlated (r = –0.66) to homocysteine levels. Conclusion: Therefore, our study shows that peripheral blood homocysteine levels can be used to predict and assess the treatment outcome in schizophrenia patients. Biomarker driven approach in schizophrenia will allow the patients to be treated promptly with the right drug. In this light, personalized treatment holds great potential in the future.
目的:了解外周血同型半胱氨酸水平与氟哌啶醇和奥氮平治疗精神分裂症的疗效及安全性的关系。材料与方法:对40例轻中度精神分裂症患者进行前瞻性随机平行组开放标签介入临床试验。为了比较奥氮平和氟哌啶醇的疗效,采用简明精神病评定量表(BPRS)评分。评估外周血同型半胱氨酸水平和异常非自愿运动量表评分。结果:两组BPRS评分在第14天和第28天均有改善。但与氟哌啶醇组相比,奥氮平组的同型半胱氨酸水平下降幅度更大(13.91±0.47至9.74±0.5)。此外,BPRS评分与同型半胱氨酸水平呈负相关(r=-0.66)。结论:因此,我们的研究表明,外周血同型半胱氨酸水平可用于预测和评估精神分裂症患者的治疗结果。精神分裂症的生物标志物驱动方法将使患者能够及时得到正确的药物治疗。有鉴于此,个性化治疗在未来具有巨大潜力。
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引用次数: 0
Treatment Considerations and Pharmacist Collaborative Care in Diabetic Ketoacidosis Management 糖尿病酮症酸中毒管理的治疗注意事项及药师协同护理
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-09-01 DOI: 10.1177/0976500X221128643
Alanood S. Algarni
Diabetic ketoacidosis (DKA) is a medical emergency caused by the lack of insulin. Metabolic acidosis, hyperglycemia, and ketoacidosis are its defining features. Insulin deficiency can cause DKA either in the presence or absence of a triggering event causing a chain of pathophysiological changes. Normalizing volume status, hyperglycemia, electrolytes, and ketoacidosis are the objectives of DKA treatment. While hospital pharmacists are involved in managing DKA, community or ambulatory care pharmacists can help to prevent DKA. Depending on the particular field of practice, a pharmacist’s engagement in DKA may involve a number of factors. Inpatient pharmacists are in a good position to help with the acute care of DKA. Because they can recognize patients who are at risk for DKA due to factors including medication nonadherence or insulin pump failure, pharmacists in the community or ambulatory-care environment play a crucial role in its prevention. When a patient finds it challenging to navigate prescription plan coverage or a lack of coverage, community pharmacists can help them obtain insulin. Regardless of the professional environment, patient education is essential. Every pharmacist has the ability to give DKA patients thorough medication education that emphasizes the value of adhering to their drug schedule, addresses any obstacles that may occur, and teaches patients how to correctly monitor their blood glucose levels. Studies showed that pharmacists’ medication counseling and treatment monitoring could improve adherence to insulin medication. The aim of this review is to provide evidence that pharmacists can contribute to optimizing medication adherence and decrease the incidence of DKA.
糖尿病酮症酸中毒(DKA)是由缺乏胰岛素引起的医疗紧急情况。代谢性酸中毒、高血糖和酮症酸中毒是其主要特征。胰岛素缺乏可在引发一系列病理生理变化的触发事件存在或不存在的情况下导致DKA。DKA治疗的目标是使容量状态正常化、高血糖、电解质和酮症酸中毒。虽然医院药剂师参与管理DKA,但社区或门诊护理药剂师可以帮助预防DKA。根据具体的执业领域,药剂师参与DKA可能涉及许多因素。住院药剂师能够很好地帮助DKA的急性护理。由于他们可以识别出因药物不依从或胰岛素泵故障等因素而有DKA风险的患者,社区或门诊护理环境中的药剂师在预防DKA方面发挥着至关重要的作用。当患者发现难以驾驭处方计划覆盖范围或缺乏覆盖范围时,社区药剂师可以帮助他们获得胰岛素。无论专业环境如何,患者教育都是必不可少的。每个药剂师都有能力为DKA患者提供全面的药物教育,强调遵守药物计划的价值,解决可能出现的任何障碍,并教患者如何正确监测血糖水平。研究表明,药剂师的药物咨询和治疗监测可以提高对胰岛素药物的依从性。这篇综述的目的是提供证据,证明药剂师可以为优化药物依从性和降低DKA的发生率做出贡献。
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引用次数: 0
Role of Nrf2 Pathway Activation in Neurological Disorder: A Brief Review Nrf2通路激活在神经系统疾病中的作用:综述
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-09-01 DOI: 10.1177/0976500X221128855
Mohammad Zubair Baba, S. Gomathy, Umair Wahedi
Oxidative stress plays a crucial role in the emergence of numerous neurodegenerative diseases, with protein accumulation and mitochondrial damage, which result in neurological disorders. To minimize oxidative stress, several defensive mechanisms protect nerve cells by releasing antioxidants such as nuclear erythroid factor2 (Nrf2)-Kelch-like ECH-associated protein1 (Keap1) signaling pathway activation has been proved to be a prospective treatment to reduce oxidative stress and neuroinflammation for protection of neurons in a variety of neurological disorders. In this review, we focus beneficial role of Nrf2 in Alzheimer’s and Parkinson’s diseases. Nrf2 is proved to be a master regulator of antioxidants by releasing over 250 cytoprotective genes aimed at oxidative stress and neuroinflammation. In animal studies Nrf2 activation is proved to improve autophagy, mitochondrial biogenesis, and Suppression of inflammatory cytokinin which protects neuronal cells and inhibit progressive neurodegeneration.
氧化应激在许多神经退行性疾病的出现中起着至关重要的作用,蛋白质积累和线粒体损伤会导致神经系统疾病。为了最大限度地减少氧化应激,几种防御机制通过释放抗氧化剂来保护神经细胞,如核红细胞因子2(Nrf2)-凯尔奇样ECH相关蛋白1(Keap1)信号通路激活已被证明是一种减少氧化应激和神经炎症的前瞻性治疗方法,用于保护各种神经疾病中的神经元。在这篇综述中,我们关注Nrf2在阿尔茨海默病和帕金森病中的有益作用。Nrf2通过释放250多个针对氧化应激和神经炎症的细胞保护基因,被证明是抗氧化剂的主要调节因子。在动物研究中,Nrf2的激活被证明可以改善自噬、线粒体生物发生和抑制炎性细胞分裂素,后者保护神经元细胞并抑制进行性神经退行性变。
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引用次数: 1
The Effect of Intravenous Ketamine After Spinal Anesthesia on the Duration of Postoperative Analgesia and Analgesic Requirement 脊髓麻醉后静脉注射氯胺酮对术后镇痛持续时间和镇痛需求的影响
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-07-10 DOI: 10.1177/0976500X221108533
A. Bagle, S. Pujari, K. Shah, Shreyank Solanki, Chandra M. Singh
Objective: To evaluate the impact of ketamine following spinal anesthesia on the duration of postoperative analgesia and the need for analgesics. Methods: This was a prospective, randomized, double-blinded placebo-controlled study done over a period of two years. A total of 60 participants undergoing elective surgeries under spinal anesthesia were randomized into two groups. After 10 min of spinal anesthesia and achieving the required level of sensory and motor blockade, both groups were given Inj. Midazolam 1 mg intravenously, followed by Inj. Ketamine 0.25 mg/kg, volume made up to 10 mL with normal saline, given intravenously for Group K and Inj. Normal Saline 10 mL was given intravenously for Group N. Hemodynamic monitoring was done intraoperatively, and the postoperative visual analog score (VAS), sedation score, the mean time for the first rescue analgesia, and the total dose of postoperative analgesic required in 24 h were tabulated. Results: There was no statistical difference between the two groups in terms of age, weight, ASA grade, and duration of surgery. In Group K, the VAS scores were significantly lower and patients were comfortable when compared to Group N (P value <.01). The mean time to first rescue analgesia was longer in Group K (6.4 ± 1.69 h) when compared to Group N (2.9 ± 1.01 h), and the total dose of postoperative analgesia (Tramadol) required in 24 h was also significantly less in Group K (143.33 ± 56.83 mg) when compared to Group N (236 ± 49.01 mg). Changes in hemodynamic parameters (heart rate and mean arterial pressure (MAP)) were statistically and clinically not significant in both the intraoperative and postoperative periods between the groups. Conclusion: Patients in Group K were more comfortable, had a longer duration of postoperative analgesia, and required less dose of rescue analgesia in the postoperative period. Ketamine is a safe drug that is readily available, and it decreases the use of opioids and opioid-related side effects. Therefore, ketamine can serve effectively as an adjunctive analgesic drug.
目的:评价脊髓麻醉后氯胺酮对术后镇痛时间和镇痛药物需求的影响。方法:这是一项前瞻性,随机,双盲安慰剂对照研究,为期两年。在脊髓麻醉下接受选择性手术的60名参与者被随机分为两组。脊髓麻醉10分钟后,达到所需的感觉和运动阻断水平后,两组均给予注射。静脉滴注咪达唑仑1mg,随后静脉注射。氯胺酮0.25 mg/kg,体积达10ml,加入生理盐水,K组和注射组静脉给予。n组静脉滴注生理盐水10 mL,术中监测血流动力学,统计术后视觉模拟评分(VAS)、镇静评分、首次抢救镇痛平均时间、术后24 h所需镇痛总剂量。结果:两组患者在年龄、体重、ASA分级、手术时间等方面无统计学差异。与N组比较,K组VAS评分明显降低,患者感觉舒适(P值< 0.01)。K组首次抢救镇痛的平均时间(6.4±1.69 h)较N组(2.9±1.01 h)更长,24 h内所需的曲马多术后总镇痛剂量(143.33±56.83 mg)较N组(236±49.01 mg)明显减少。两组患者术中术后血流动力学参数(心率和平均动脉压(MAP))的变化均无统计学意义和临床意义。结论:K组患者更舒适,术后镇痛持续时间更长,术后需要的抢救镇痛剂量更少。氯胺酮是一种安全易得的药物,它可以减少阿片类药物的使用和阿片类药物相关的副作用。因此,氯胺酮可以作为一种有效的辅助镇痛药物。
{"title":"The Effect of Intravenous Ketamine After Spinal Anesthesia on the Duration of Postoperative Analgesia and Analgesic Requirement","authors":"A. Bagle, S. Pujari, K. Shah, Shreyank Solanki, Chandra M. Singh","doi":"10.1177/0976500X221108533","DOIUrl":"https://doi.org/10.1177/0976500X221108533","url":null,"abstract":"Objective: To evaluate the impact of ketamine following spinal anesthesia on the duration of postoperative analgesia and the need for analgesics. Methods: This was a prospective, randomized, double-blinded placebo-controlled study done over a period of two years. A total of 60 participants undergoing elective surgeries under spinal anesthesia were randomized into two groups. After 10 min of spinal anesthesia and achieving the required level of sensory and motor blockade, both groups were given Inj. Midazolam 1 mg intravenously, followed by Inj. Ketamine 0.25 mg/kg, volume made up to 10 mL with normal saline, given intravenously for Group K and Inj. Normal Saline 10 mL was given intravenously for Group N. Hemodynamic monitoring was done intraoperatively, and the postoperative visual analog score (VAS), sedation score, the mean time for the first rescue analgesia, and the total dose of postoperative analgesic required in 24 h were tabulated. Results: There was no statistical difference between the two groups in terms of age, weight, ASA grade, and duration of surgery. In Group K, the VAS scores were significantly lower and patients were comfortable when compared to Group N (P value <.01). The mean time to first rescue analgesia was longer in Group K (6.4 ± 1.69 h) when compared to Group N (2.9 ± 1.01 h), and the total dose of postoperative analgesia (Tramadol) required in 24 h was also significantly less in Group K (143.33 ± 56.83 mg) when compared to Group N (236 ± 49.01 mg). Changes in hemodynamic parameters (heart rate and mean arterial pressure (MAP)) were statistically and clinically not significant in both the intraoperative and postoperative periods between the groups. Conclusion: Patients in Group K were more comfortable, had a longer duration of postoperative analgesia, and required less dose of rescue analgesia in the postoperative period. Ketamine is a safe drug that is readily available, and it decreases the use of opioids and opioid-related side effects. Therefore, ketamine can serve effectively as an adjunctive analgesic drug.","PeriodicalId":16761,"journal":{"name":"Journal of Pharmacology & Pharmacotherapeutics","volume":"13 1","pages":"278 - 283"},"PeriodicalIF":0.2,"publicationDate":"2022-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42233239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antiemetic Efficacy of Prophylactic Ondansetron Versus Ondansetron with Dexamethasone Combination Therapies in Women Undergoing Breast Surgeries: A Randomized Controlled Trial 预防性昂丹司琼与昂丹司酮联合地塞米松治疗乳腺外科女性的止吐效果:一项随机对照试验
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-06-01 DOI: 10.1177/0976500X221105758
A. Shivanna, R. Kadni, Syed Farzan Tausif, Varghese K. Zachariah
Objective: To compare the prophylactic antiemetic efficacy of ondansetron monotherapy with that of the combination of ondansetron and dexamethasone in the prevention on postoperative nausea and vomiting (PONV) in breast surgeries by observing the incidence of PONV, assess the percentage of participants requiring rescue antiemetics, know the side effects of drugs, and analyze the effect of the surgical duration of breast surgeries. Methods: The group ondansetron (O) received 0.1 mg/kg IV ondansetron and the other group (ondansetron and dexamethasone combination, OD) received 0.1 mg/kg IV ondansetron and 0.1 mg/kg of dexamethasone. The incidence of PONV in the first 24 h, percentage of population receiving rescue antiemetics, surgical duration, and hemodynamic parameters were noted. Results: In the 0 h to 6 h postoperative period, 38.9% of participants of group O had PONV, whereas only 13.9% in group OD had PONV, which was statistically significant (P < .016). About 30.6% of study population in group O and 8.3% in group OD required rescue antiemetics which was statistically significant (P = .017). Surgical duration of more than 120 min had a statistically significant higher incidence of PONV in the O group with a P-value of .048. Conclusion: The combination of prophylactic ondansetron with dexamethasone is more efficacious than ondansetron alone for the prevention of PONV in women undergoing breast surgeries.
目的:通过观察乳腺手术术后恶心呕吐(PONV)的发生率,评估需要抢救性止吐药物的参与者百分比,了解药物的副作用,比较昂丹司琼单药治疗与昂丹司酮和地塞米松联合治疗在预防乳腺手术后恶心呕吐中的预防性止吐效果,并分析乳腺手术时间的影响。方法:昂丹司琼(O)组静脉注射昂丹司酮0.1mg/kg,另一组(昂丹司隆与地塞米松联合用药,OD)静脉注射昂丹司琼0.1mg/kg和地塞米松0.1mg/kg。注意前24小时PONV的发生率、接受止吐药物抢救的人群百分比、手术持续时间和血液动力学参数。结果:术后0~6h,O组有38.9%的受试者出现PONV,而OD组只有13.9%的受试人出现PONV,具有统计学意义(P<.016)。O组约30.6%的研究人群和OD组约8.3%的研究人群需要抢救性止吐药物,具有统计学意义,(P=.017)。手术时间超过120分钟的O组PONV发生率具有统计学意义更高,P值为.048。结论:预防性昂丹司琼联合地塞米松预防乳腺手术妇女PONV的疗效优于单独应用昂丹司酮。
{"title":"Antiemetic Efficacy of Prophylactic Ondansetron Versus Ondansetron with Dexamethasone Combination Therapies in Women Undergoing Breast Surgeries: A Randomized Controlled Trial","authors":"A. Shivanna, R. Kadni, Syed Farzan Tausif, Varghese K. Zachariah","doi":"10.1177/0976500X221105758","DOIUrl":"https://doi.org/10.1177/0976500X221105758","url":null,"abstract":"Objective: To compare the prophylactic antiemetic efficacy of ondansetron monotherapy with that of the combination of ondansetron and dexamethasone in the prevention on postoperative nausea and vomiting (PONV) in breast surgeries by observing the incidence of PONV, assess the percentage of participants requiring rescue antiemetics, know the side effects of drugs, and analyze the effect of the surgical duration of breast surgeries. Methods: The group ondansetron (O) received 0.1 mg/kg IV ondansetron and the other group (ondansetron and dexamethasone combination, OD) received 0.1 mg/kg IV ondansetron and 0.1 mg/kg of dexamethasone. The incidence of PONV in the first 24 h, percentage of population receiving rescue antiemetics, surgical duration, and hemodynamic parameters were noted. Results: In the 0 h to 6 h postoperative period, 38.9% of participants of group O had PONV, whereas only 13.9% in group OD had PONV, which was statistically significant (P < .016). About 30.6% of study population in group O and 8.3% in group OD required rescue antiemetics which was statistically significant (P = .017). Surgical duration of more than 120 min had a statistically significant higher incidence of PONV in the O group with a P-value of .048. Conclusion: The combination of prophylactic ondansetron with dexamethasone is more efficacious than ondansetron alone for the prevention of PONV in women undergoing breast surgeries.","PeriodicalId":16761,"journal":{"name":"Journal of Pharmacology & Pharmacotherapeutics","volume":"13 1","pages":"182 - 189"},"PeriodicalIF":0.2,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42829496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Silico Modeling and Docking Analysis of CTX-M-5, Cefotaxime-Hydrolyzing β-Lactamase from Human-Associated Salmonella Typhimurium 头孢噻肟水解鼠伤寒沙门氏菌β-内酰胺酶CTX-M-5的原位建模和对接分析
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-06-01 DOI: 10.1177/0976500X221109721
S. K. Md. Jasmine, V. Reddy G., Neelima Gorityala, S. Sagurthi, Sandhya Mungapati, Kota Neela Manikanta, U. Allam
Objective: To computationally model the CTX-M-5 β-lactamase and establish its structure, which is exclusively present in human-associated Salmonella. Methods: The CTX-M-5 aminoacid sequence (Uniprot ID:O65975) of Salmonella enterica subsp. enterica serovar typhimurium was retrieved from UniProt database and subjected to homology modeling using MODELLER 9v7. The homology models were duly validated using RAMPAGE tool by generating Ramachandran plots, ERRAT graphs, and ProSA score. DoGSiteScorer server and ConSurf server were used to detect the cavities, pockets, and clefts to identify conserved amino acid sites in the predicted model. Subsequently, the modeled structure was docked using CLC Drug Discovery Workbench against proven drugs and known inhibitors. Results: Obtained high-quality homology model with 91.7% of the residues in favorable regions in Ramachandran plot and qualified in other quality parameters. Docking studies resulted in a higher dock score for PNK (D-benzylpenicilloic acid) molecule when compared to other reported inhibitors. Conclusion: This in silico study suggests that the compound PNK could be an efficient ligand for CTX-M-5 β-lactamase and serve as a potent inhibitor of CTX-M-5.
目的:对CTX-M-5β-内酰胺酶进行计算建模,并建立其结构,该酶仅存在于人相关沙门氏菌中。方法:对肠炎沙门氏菌亚种CTX-M-5氨基酸序列(Uniprot ID:O65975)进行测序。从UniProt数据库中检索鼠伤寒肠炎血清型,并使用MODELLER 9v7进行同源性建模。通过生成Ramachandran图、ERRAT图和ProSA评分,使用RAMPAGE工具对同源性模型进行了适当验证。DoGSiteScorer服务器和ConSurf服务器用于检测空腔、口袋和切口,以确定预测模型中的保守氨基酸位点。随后,使用CLC药物发现工作台针对已证实的药物和已知的抑制剂对接建模的结构。结果:获得了高质量的同源性模型,Ramachandran图中有利区域的残基占91.7%,其他质量参数合格。与其他报道的抑制剂相比,对接研究导致PNK(D-苄基青霉酸)分子的对接得分更高。结论:该化合物PNK是CTX-M-5β-内酰胺酶的有效配体,是CTX-M-5的有效抑制剂。
{"title":"In Silico Modeling and Docking Analysis of CTX-M-5, Cefotaxime-Hydrolyzing β-Lactamase from Human-Associated Salmonella Typhimurium","authors":"S. K. Md. Jasmine, V. Reddy G., Neelima Gorityala, S. Sagurthi, Sandhya Mungapati, Kota Neela Manikanta, U. Allam","doi":"10.1177/0976500X221109721","DOIUrl":"https://doi.org/10.1177/0976500X221109721","url":null,"abstract":"Objective: To computationally model the CTX-M-5 β-lactamase and establish its structure, which is exclusively present in human-associated Salmonella. Methods: The CTX-M-5 aminoacid sequence (Uniprot ID:O65975) of Salmonella enterica subsp. enterica serovar typhimurium was retrieved from UniProt database and subjected to homology modeling using MODELLER 9v7. The homology models were duly validated using RAMPAGE tool by generating Ramachandran plots, ERRAT graphs, and ProSA score. DoGSiteScorer server and ConSurf server were used to detect the cavities, pockets, and clefts to identify conserved amino acid sites in the predicted model. Subsequently, the modeled structure was docked using CLC Drug Discovery Workbench against proven drugs and known inhibitors. Results: Obtained high-quality homology model with 91.7% of the residues in favorable regions in Ramachandran plot and qualified in other quality parameters. Docking studies resulted in a higher dock score for PNK (D-benzylpenicilloic acid) molecule when compared to other reported inhibitors. Conclusion: This in silico study suggests that the compound PNK could be an efficient ligand for CTX-M-5 β-lactamase and serve as a potent inhibitor of CTX-M-5.","PeriodicalId":16761,"journal":{"name":"Journal of Pharmacology & Pharmacotherapeutics","volume":"13 1","pages":"135 - 147"},"PeriodicalIF":0.2,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42869683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
The Association Between Serum Vitamin D Levels and Serum Cathelicidin Antimicrobial Peptide (CAMP) Levels Among Tuberculosis Patients in Comparison with Control Subjects 结核病患者与对照组血清维生素D水平与血清Cathelicidin抗菌肽(CAMP)水平的相关性
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-06-01 DOI: 10.1177/0976500X221105760
Kiran Belur, P. Arunachalam, Jamuna Rani Raveendran
Objectives: To compare the serum vitamin D and serum cathelicidin antimicrobial peptide (CAMP) levels among tuberculosis patients and healthy subjects and to determine the association between serum vitamin D and cathelicidin in tuberculosis. Materials and Methods: This is a case-control study carried out at the pulmonary medicine and pediatrics departments of a tertiary care hospital in Chengalpattu. The study included 180 tuberculosis cases and 90 control subjects of both sexes between the age group of 1 to 80 years. Serum was used to estimate vitamin D and CAMP. The study was analyzed using SPSS version 21 (IBM Corp. Armonk, New York). The results were evaluated using the chi-square test at a 95% confidence interval, and P value <.05 was considered highly significant. Results: This study observed vitamin D deficiency, vitamin D insufficiency, and optimum vitamin D among 55%, 41%, and 3.89% tuberculosis cases, respectively. Similarly, vitamin D deficiency, vitamin D insufficiency, and optimum vitamin D were seen in 40%, 50%, and 10% healthy controls, respectively. Conclusion: This study found no association between serum vitamin D and serum CAMP levels in tuberculosis patients and healthy controls.
目的:比较结核病患者与健康人血清维生素D和抗菌肽(CAMP)水平,探讨结核病患者血清维生素D与抗菌肽的关系。材料和方法:这是一项在成都某三级医院肺内科和儿科进行的病例对照研究。该研究包括180例结核病病例和90例对照受试者,年龄在1至80岁之间。血清测定维生素D和CAMP。该研究使用SPSS版本21 (IBM Corp. Armonk, New York)进行分析。结果采用卡方检验,置信区间为95%,P值<。0.05被认为是非常显著的。结果:55%、41%和3.89%的结核病患者存在维生素D缺乏、维生素D不足和维生素D适宜。同样,维生素D缺乏、维生素D不足和最佳维生素D分别出现在40%、50%和10%的健康对照中。结论:本研究未发现结核病患者和健康对照者血清维生素D和血清CAMP水平之间存在关联。
{"title":"The Association Between Serum Vitamin D Levels and Serum Cathelicidin Antimicrobial Peptide (CAMP) Levels Among Tuberculosis Patients in Comparison with Control Subjects","authors":"Kiran Belur, P. Arunachalam, Jamuna Rani Raveendran","doi":"10.1177/0976500X221105760","DOIUrl":"https://doi.org/10.1177/0976500X221105760","url":null,"abstract":"Objectives: To compare the serum vitamin D and serum cathelicidin antimicrobial peptide (CAMP) levels among tuberculosis patients and healthy subjects and to determine the association between serum vitamin D and cathelicidin in tuberculosis. Materials and Methods: This is a case-control study carried out at the pulmonary medicine and pediatrics departments of a tertiary care hospital in Chengalpattu. The study included 180 tuberculosis cases and 90 control subjects of both sexes between the age group of 1 to 80 years. Serum was used to estimate vitamin D and CAMP. The study was analyzed using SPSS version 21 (IBM Corp. Armonk, New York). The results were evaluated using the chi-square test at a 95% confidence interval, and P value <.05 was considered highly significant. Results: This study observed vitamin D deficiency, vitamin D insufficiency, and optimum vitamin D among 55%, 41%, and 3.89% tuberculosis cases, respectively. Similarly, vitamin D deficiency, vitamin D insufficiency, and optimum vitamin D were seen in 40%, 50%, and 10% healthy controls, respectively. Conclusion: This study found no association between serum vitamin D and serum CAMP levels in tuberculosis patients and healthy controls.","PeriodicalId":16761,"journal":{"name":"Journal of Pharmacology & Pharmacotherapeutics","volume":"13 1","pages":"175 - 181"},"PeriodicalIF":0.2,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44677075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacokinetics of a Novel Sustained-Release Vitamin C Oral Tablet: A Single Dose, Randomized, Double-Blind, Placebo-Controlled Trial 新型维生素C缓释口服片的药代动力学:单剂量、随机、双盲、安慰剂对照试验
IF 0.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2022-06-01 DOI: 10.1177/0976500X221111669
Shah Rajat, S. Thanawala, R. Abiraamasundari
Objectives To evaluate the pharmacokinetics of a novel sustained-release oral tablet (C-Fence, Inventia Healthcare Limited, Mumbai, India). Methods We conducted a randomized, placebo-controlled, parallel-design, 500 mg single-dose pharmacokinetic study of this new preparation in 18 healthy adult human subjects (nine in each group) under fasting conditions. The concentration-time profile and pharmacokinetic parameters of L-ascorbic acid, including Cmax (maximum plasma concentration), Tmax (time to reach Cmax), and AUC0-24h (area under the plasma concentration versus time curve from time 0 h to 24 h) were calculated using baseline-corrected values. Results The sustained-release tablets resulted in mean Cmax and AUC0-24h, respectively, of 1.39 ± 1.21 µg/mL and 11.72 ± 10.73 µg.h/mL against 0.18 ± 0.10 µg/mL and 0.89 ± 0.27 µg.h/mL, respectively, in the placebo group. The mean Tmax with the sustained-release tablets was 4.3 ± 2.5 h. At 12, 16, and 24 h from dosing, the concentrations were 0.6, 0.4, and 0.3 µg/mL, respectively, above baseline values. Conclusion Novel sustained-release formulations of vitamin C are expected to help achieve plasma vitamin C values above the homeostatic saturation level and result in higher steady-state plasma concentration, which might result in better cellular uptake.
目的评价一种新型缓释口服片剂(C-Fence,Inventia Healthcare Limited,孟买,印度)的药代动力学。方法我们在禁食条件下对18名健康成年受试者(每组9名)进行了这种新制剂的随机、安慰剂对照、平行设计、500mg单剂量药代动力学研究。使用基线校正值计算L-抗坏血酸的浓度-时间曲线和药代动力学参数,包括Cmax(最大血浆浓度)、Tmax(达到Cmax的时间)和AUC0-24h(从0小时到24小时的血浆浓度与时间曲线下的面积)。结果缓释片的平均Cmax和AUC0-24h分别为1.39±1.21µg/mL和11.72±10.73µg.h/mL,而安慰剂组分别为0.18±0.10µg/mL和0.89±0.27µg.h/mL。缓释片的平均Tmax为4.3±2.5小时。给药后12、16和24小时,浓度分别为0.6、0.4和0.3µg/mL,高于基线值。结论新型维生素C缓释制剂有望帮助实现血浆维生素C值高于稳态饱和水平,并导致更高的稳态血浆浓度,这可能导致更好的细胞摄取。
{"title":"Pharmacokinetics of a Novel Sustained-Release Vitamin C Oral Tablet: A Single Dose, Randomized, Double-Blind, Placebo-Controlled Trial","authors":"Shah Rajat, S. Thanawala, R. Abiraamasundari","doi":"10.1177/0976500X221111669","DOIUrl":"https://doi.org/10.1177/0976500X221111669","url":null,"abstract":"Objectives To evaluate the pharmacokinetics of a novel sustained-release oral tablet (C-Fence, Inventia Healthcare Limited, Mumbai, India). Methods We conducted a randomized, placebo-controlled, parallel-design, 500 mg single-dose pharmacokinetic study of this new preparation in 18 healthy adult human subjects (nine in each group) under fasting conditions. The concentration-time profile and pharmacokinetic parameters of L-ascorbic acid, including Cmax (maximum plasma concentration), Tmax (time to reach Cmax), and AUC0-24h (area under the plasma concentration versus time curve from time 0 h to 24 h) were calculated using baseline-corrected values. Results The sustained-release tablets resulted in mean Cmax and AUC0-24h, respectively, of 1.39 ± 1.21 µg/mL and 11.72 ± 10.73 µg.h/mL against 0.18 ± 0.10 µg/mL and 0.89 ± 0.27 µg.h/mL, respectively, in the placebo group. The mean Tmax with the sustained-release tablets was 4.3 ± 2.5 h. At 12, 16, and 24 h from dosing, the concentrations were 0.6, 0.4, and 0.3 µg/mL, respectively, above baseline values. Conclusion Novel sustained-release formulations of vitamin C are expected to help achieve plasma vitamin C values above the homeostatic saturation level and result in higher steady-state plasma concentration, which might result in better cellular uptake.","PeriodicalId":16761,"journal":{"name":"Journal of Pharmacology & Pharmacotherapeutics","volume":"13 1","pages":"167 - 174"},"PeriodicalIF":0.2,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48380505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Pharmacology & Pharmacotherapeutics
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