<b>Background/Objectives</b>: Monoclonal antibodies targeting the PD-1/PD-L1 immune checkpoint have achieved clinical success but face drawbacks such as poor oral bioavailability, limited tumor penetration, and immune-related adverse events. Small-molecule inhibitors present a promising alternative that may overcome these challenges. <b>Methods</b>: Here, an integrated computational framework combining ligand-based pharmacophore modeling and structure-based molecular docking was utilized to screen a comprehensive library consisting of traditional Chinese medicine-derived compounds and clinically approved drugs. The binding affinity between identified candidate compounds and PD-L1 was quantitatively assessed using bio-layer interferometry (BLI). In vitro cytotoxicity assays were conducted on A549 human lung carcinoma and LLC mouse lung carcinoma cell lines. In vivo antitumor efficacy was evaluated in LLC tumor-bearing mice through measurement of tumor growth inhibition, serum cytokine levels (IFN-γ and IL-4) by ELISA, and expression levels of IFN-γ and granzyme B (GZMB) within tumor tissues via immunohistochemistry. <b>Results</b>: In vitro, anidulafungin exhibited anti-tumor effects against both human lung cancer A549 cells and mouse Lewis lung carcinoma (LLC) tumor cells, with IC<sub>50</sub> values of 170.6 µg/mL and 160.9 µg/mL, respectively. The BLI analysis revealed a dissociation constant (K<sub>D</sub>) of 76.9 μM, indicating a high affinity of anidulafungin for PD-L1. In vivo, anidulafungin significantly increased serum levels of IFN-γ and IL-4 in tumor-bearing mice and elevated expression of IFN-γ and granzyme B (GZMB) in tumor tissues, confirming its immune-mediated anti-tumor effects. <b>Conclusions</b>: Anidulafungin represents a promising small-molecule PD-L1 inhibitor, demonstrating significant anti-tumor potential via immune activation and highlighting the feasibility of repurposing approved drugs for cancer immunotherapy.
Objective: To analyze the hotspots, patterns, and distribution of research on the safety and risk of antibody preparations in the past 20 years. It also seeks to summarize the current status and trends of research on the safety and risk control of antibody preparations. Methods: Taking “antibody preparation”, “safety” and “risk” as keywords, relevant articles were searched in the databases Web of Science. CiteSpace was utilized to analyze the annual number of publications, countries, authors, institutions, highly cited literature and keywords of the screened literature, and the relevant maps were drawn and the results were analyzed. Results: A total of 1693 articles were included. The annual number of publications in the field of antibody preparation safety has shown stable growth followed by a rapid increase between 2002 and 2022. Among the countries, the United States accounted for 36.7% of the total publications, ranking first in the world. Large foreign pharmaceutical companies, research institutions, comprehensive university and their affiliated hospitals were the most high-yield institutions. Current hot topics in the field of antibody preparation safety research include “ADC”, “monoclonal antibody”, “anti-tumor activity”, “immunotherapy”, etc. Conclusion: Over the past 20 years, research on antibody formulations has garnered increasing attention both domestically and internationally, with a focus mainly on efficacy and safety. There has been relatively little research on risk control. In the future, more in-depth research is needed on the mechanisms of adverse reactions in antibody formulations to provide more effective strategies for risk control.
Pharmacy and materia medica, Therapeutics. Pharmacology
The Pakistani pharmaceutical industry cannot ignore the contribution of pharmaceutical multinational corporations (MNCs) in terms of innovation and access to advanced treatments. The sale of a pharmaceutical manufacturing plant by an MNC to a Pakistani company has again sparked a debate on why MNCs are closing manufacturing operations in the country. National firms are currently giving MNCs a tough time in Pakistan. Besides competition, MNCs face mergers and acquisitions that hinder the expansion of existing facilities. In the recent past, there has been a noticeable shift in the market shares of multinational corporations (MNCs) and local companies. The market share of national firms has gradually increased, reaching 74.51%, while the market share of MNCs has decreased, falling to 25.49%. These local companies have increasingly partnered with foreign companies through joint ventures, which has had a positive impact on their growth and market share. Nevertheless, the federal government recently deregulated prices for non-essential medicines, so it is expected that MNCs will show their commitment to Pakistan by investing in the country. Investing in new molecules and infrastructure is necessary for MNCs in order to maintain their position in the market. Infrastructure investment is crucial for the smooth operation of pharmaceutical firms. This includes the construction of state-of-the-art manufacturing facilities, the establishment of research and development centres, and the upgrading of technology.
Therapeutics. Pharmacology, Pharmacy and materia medica
Poonam Kumari, Amarjeet Kumar, Chandni Sinha
et al.
Background and Aims:
Both operating table height and patient level in relation to the anesthesiologist influence supraglottic airway device (SAD) insertion and task performance in terms of physical and mental workload. The aim of the study was to find out the appropriate table height during SAD insertion in terms of time taken for insertion, success rate, ease of insertion, and anesthesiologist comfort.
Material and Methods:
In this randomized controlled trial, 90 American Society of Anesthesiologists physical status I and II patients, aged between 18 and 60 years, scheduled for elective surgery were recruited. Patients were divided into three groups of 30 each. During SAD insertion, the table height was adjusted so that the patient’s forehead was at the level of 5 cm above the xiphoid process in group I, at the level of the xiphoid process in group II, and at the level of 5 cm below the xiphoid process in group III of the anesthesiologist. We measured SAD insertion time, first attempt success rate, ease of insertion, and anesthesiologist comfort during the procedure.
Results:
The SAD insertion time (in seconds) was lower in group III than in groups I and II, and a significant difference was found between the groups (P < 0.05). The mean ease of insertion score, anesthesiologist comfort, and the first-attempt success rate of SAD insertion were higher in group III than in groups I and II, and the difference among the groups was statistically significant (P < 0.05).
Conclusions:
We conclude that the lower table height with the patient’s forehead at the level of 5 cm below the xiphoid process of the anesthesiologist is ergonomically more efficient during SAD (I-gel) insertion. This table height is also more comfortable for the anesthesiologist during SAD placement.
Markus Hovd, Ida Robertsen, Jean-Baptiste Woillard
et al.
In combination with Bayesian estimates based on a population pharmacokinetic model, limited sampling strategies (LSS) may reduce the number of samples required for individual pharmacokinetic parameter estimations. Such strategies reduce the burden when assessing the area under the concentration versus time curves (AUC) in therapeutic drug monitoring. However, it is not uncommon for the actual sample time to deviate from the optimal one. In this work, we evaluate the robustness of parameter estimations to such deviations in an LSS. A previously developed 4-point LSS for estimation of serum iohexol clearance (i.e., dose/AUC) was used to exemplify the effect of sample time deviations. Two parallel strategies were used: (a) shifting the exact sampling time by an empirical amount of time for each of the four individual sample points, and (b) introducing a random error across all sample points. The investigated iohexol LSS appeared robust to deviations from optimal sample times, both across individual and multiple sample points. The proportion of individuals with a relative error greater than 15% (P15) was 5.3% in the reference run with optimally timed sampling, which increased to a maximum of 8.3% following the introduction of random error in sample time across all four time points. We propose to apply the present method for the validation of LSS developed for clinical use.
Krzysztof Wierzbicki, Cezary Linart, Monika Bugdol
et al.
Introduction: Carpal tunnel syndrome (CTS) is an upper limb neuropathy that occurs as a result of compression of the median nerve in the carpal tunnel and is the most common mononeuropathy in the general population. The aim of the study was to assess the electrophysiological parameters of the median nerve before and 6 months after surgical treatment of CTS in patients with a history of smoking and comorbidities.
Material and methods: 84 patients with CTS who were eligible for surgery were enrolled in this prospective study. Electrophysiological tests were performed in the patients before and 6 months after surgery for CTS.
Results: The results of the study prove that smoking and diabetes significantly worsen the electrophysiological parameters in patients undergoing surgical treatment of CTS.
Conclusions: Smoking and diabetes cause a significantly worse prognosis in patients after surgery for CTS.
Stefano Russo, Cristina Torrisi, Nunzio Cardullo
et al.
Colorectal cancer is one of the most diffused tumoral diseases. Since most medicaments employed for its treatment are debilitating, the use of naturally derived products, which can be effective against the mutated cells and, in addition, can reduce most inflammatory-related effects, could be extremely beneficial for the continued treatment of this disease. In this research, ethyl protocatechuate (PCAEE), a protocatechuic acid prodrug, was encapsulated in solid lipid nanoparticles (SLN) (prepared without and with Tween 80), which were characterized in terms of size, polydispersity index (PDI), zeta potential and thermotropic behavior. Encapsulation efficiency, release profile and interaction with a model of biomembrane were also assessed. The nanoparticles were tested in vitro on both healthy cells and on a model of tumoral cells. SLN prepared with Tween 80 was promising in terms of physicochemical properties (z-average of 190 nm, PDI 0.150 and zeta potential around −20 mV) and encapsulation efficiency (56%); they showed a desirable release profile, demonstrated an ability to penetrate and release the encapsulated PCAEE into a biomembrane model and were nontoxic on healthy cells. In addition, they caused a greater dose-dependent decrease in the viability of CaCo-2 cells than PCAEE alone. In conclusion, the formulation could be proposed for further studies to assess its suitability for the treatment of colorectal cancer.
Background: Urinary tract infection (UTI) is a common health problem in both community and nosocomial settings. However, the predisposing factors which are responsible for production of extended spectrum beta-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae makes the treatment option narrow and cause multidrug resistance.
Aim and Objectives: This study demonstrate various risk factors associated with multidrug resistance in Enterobacteriaceae from UTI at tertiary care center in Gujarat.
Material and Methods: A retrospective observational study was conducted at a tertiary-care hospital. Urine samples were received from various departments and outpatient department (OPD). Organisms from Enterobacteriaceae group were isolated and identified by various biochemical methods. ESBL and Carbapenemase producing organisms were then processed for Antibiotic susceptibility test as per CLSI guideline.
Results: A total of 196 Enterobacteriaceae organisms were isolated from processed urine samples of tertiary care Hospitals. The most prevalent in people aged 45–65 years (36%) followed by those aged 17–30 (22%) years. UTI due to ESBL and Carbapenemase producer are more isolated in female (28%, 11%) as compare to male (16%, 6%). Indoor patients had higher prevalence of ESBL (29%) and carbapenemases (10%) isolation compare to OPD patient (ESBL-15%, Carbapenemases-7%) and among them most common ward was medicine department. The most common predisposing factor was catheterization followed by diabetes mellitus and obstructive uropathy.
Conclusion: High prevalence of ESBL and Carbapenemase producing Enterobacteriaceae is found in Indoor patients than OPD patients. Most of these patients are from Medicine department. Catheterization is the most common risk factor associated with ESBL and carbapenemase producing organism. [Natl J Physiol Pharm Pharmacol 2023; 13(6.000): 1304-1307]
Therapeutics. Pharmacology, Pharmacy and materia medica
Franciane Souza Guedes, Margareth Hamdan Melo Coelho, Lilia Maria Caldas Embiruçu
et al.
A terapia inalatória tem papel central no tratamento da doença pulmonar obstrutiva crônica (DPOC). O manejo correto dos dispositivos inalatórios é fundamental para deposição pulmonar eficiente dos agentes farmacológicos, e consequentemente, para a efetividade do tratamento da doença.1,2 Entretanto, muitos pacientes podem não utilizar corretamente os inaladores. A técnica inalatória incorreta é associada a desfechos negativos, pior qualidade de vida e maior utilização dos recursos de saúde em pacientes com DPOC.1-4 Dados sobre o manuseio dos dispositivos inalatórios entre indivíduos com DPOC são escassos em nosso meio, sobretudo, no contexto da prática clínica. O objetivo do estudo foi avaliar o domínio da técnica entre pacientes com DPOC grave em uso de dois diferentes dispositivos inalatórios (Respimat® e Diskus®).
Pharmacy and materia medica, Pharmaceutical industry
Nikoleta Đorđevski, Abdullahi Ibrahim Uba, Gokhan Zengin
et al.
This study was designed to investigate the impact of different extraction solvent systems on the chemical composition and biological activities of <i>Allium scorodoprasum</i> L. (Amaryllidaceae)—the medicinal plant that was traditionally used as a remedy in the medieval period in the Balkans. Targeted chemical analysis of nine different extracts was performed by UHPLC(−)HESI–QqQ-MS/MS. Antimicrobial and antibiofilm activities of the extracts were investigated on sixteen clinical isolates of bacteria, yeasts and dermatomycetes, all isolated from infected human skin and corneal formations. Cytotoxicity and wound-healing properties were tested on human immortalized keratinocytes (HaCaT cell line). Antioxidant activity was assessed by six different assays, while beneficial potential against certain neurodegenerative diseases and type 2 diabetes was determined in selected enzyme inhibition assays coupled with molecular modeling. The results showed that the obtained extracts were rich in phenolic compounds, especially flavonoid glycosides such as rutin and kaempferol 3-<i>O</i>-glucoside. All of the extracts showed antimicrobial, wound-healing, antioxidant and anti-enzymatic properties. This study is the first of its kind, linking the medieval medicinal use of wild-growing flowers of <i>A. scorodoprasum</i> with contemporary in vitro scientific approaches.
Andri Wardiana, Martina L Jones, Stephen M Mahler
et al.
The traditional chemotherapy drug has been used as a standard cancer treatment, however it has resulted a modest survival benefit and damaged non-cancerous cells. Thus, the novel strategies which can improve selectivity and specificity in chemotherapy are urgently needed. Antibody drug conjugate (ADC) combines monoclonal antibody and cytotoxic drug is a potential regimen as targeted therapy. However, the heterogeneous mixtures has been observed using the current ADC methods. Here, we develop the strategy for generation a stable ADC utilising modified single chain antibody fragment (scFv) containing azide group for click chemistry reaction with alkyne containing cytotoxic drug. This research focused on targeting prostate cancer as a model disease utilising targeting prostate specific membrane antigen (PSMA) receptor which is overexpressed in all prostate cancer stages. The unnatural amino acid para-azido phenyl alanine (pAzF) has been successfully incorporated into anti-PSMA J591 scFv and specifically bound and internalised into PSMA positive cancer cells. This mutant scFv were also successfully conjugated into a linker containing cyclo-alkyne, DBCO-PEG4-DBCO as a model for creating ADC through copper-free click chemistry reaction. This bioconjugation method is promising as a versatile strategy for generating a stable ADC to improve therapeutic efficacy in cancer treatment.
Schisandrol A possesses pharmacological properties and is used to treat various diseases; however, its effects on osteoarthritis (OA) progression remain unclear. Here, we investigated Schisandrol A as a potential therapeutic agent for OA. In vitro, Schisandrol A effects were confirmed based on the levels of expression of catabolic factors (MMPs, ADAMTS5, and Cox2) induced by IL-1β or Schisandrol A treatment in chondrocytes. In vivo, experimental OA in mice was induced using a destabilized medial meniscus (DMM) surgical model or oral gavage of Schisandrol A in a dose-dependent manner, and demonstrated using histological analysis. In vitro and in vivo analyses demonstrated that Schisandrol A inhibition attenuated osteoarthritic cartilage destruction via the regulation of Mmp3, Mmp13, Adamts5, and Cox2 expression. In the NF-κB signaling pathway, Schisandrol A suppressed the degradation of IκB and the phosphorylation of p65 induced by IL-1β. Overall, and Schisandrol A reduced the expression of catabolic factors by blocking NF-κB signaling and prevented cartilage destruction. Therefore, Schisandrol A attenuated OA progression, and can be used to develop novel OA drug therapies.
Should decision making in health care, notably in respect of the allocation of resources between individuals and disease states, rest on notions of the burden of disease and denial of care as assessed by societal evaluations or on the extent to which the need of patients and caregivers is fulfilled. The prospect of the denial of health care, for those deemed ‘unworthy’ has a long history in the eugenics movement. Many have assumed that this ‘utilitarian aberration’ has long been discredited. Unfortunately, once the question of the allocation of limited health care resources is considered it reasserts itself; manifested in the creation of health state preferences and states worse than death, and application of the cost-per-QALY calculus driving claims for pricing and access. In the US, this focus on cost-per-QALY claims is most closely associated with the Institute for Clinical and Economic Review (ICER) with its regular clinical assessments and modelled imaginary simulations supporting recommendations which, in many if not most cases, give support to the denial of care. The purpose of this commentary is to point to the unfortunate similarities between ‘eugenic’ decision making and the application of thresholds in burden of illness cost-per-QALY exercises. If we are to finally rid ourselves of a ‘eugenic’ approach to health care resource allocation, then we must abandon preferences and the QALY calculus.
Background: The mind map (MM) is a powerful graphic technique that can be applied to improve learning and clearer thinking. MMs can be used as self-learning methods that facilitate understanding of difficult concepts. A learning strategy underutilized in medical education is MM. MMs are multisensory tools that may help medical students organize, integrate, and retain information. Recent work suggests that using MM as a note-taking strategy facilitates critical thinking.
Aims and Objectives: Our objective was to evaluate the effectiveness of using MMs as a self-learning method for the 1st year MBBS students.
Materials and Methods: A total of 60 1st year MBBS students were randomly selected and assigned to two equal groups (MM vs. usual study technique). A text on glucose homeostasis was selected as self-study material. The MM group was given a 45-min lesson in the technique. Both groups were exposed to the study text for a 45-min period and were requested to answer four structured questions based on the study text.
Results: There was no significant difference between the test scores of two groups. The average marks obtained by the MM group were 30.97 ± 0.40. It was 32 ± 0.32 in the usual study technique group. Majority from the MM group felt that it is useful to summarize information and active learning. They wanted to study further about MM and use it in other subjects.
Conclusion: MM technique is not superior in newly admitted medical students for short-term learning; however, most students reported it as a useful learning tool in active learning. [Natl J Physiol Pharm Pharmacol 2018; 8(4.000): 479-483]
Therapeutics. Pharmacology, Pharmacy and materia medica
Mokhtar Bishr, Mohamed El-Degwy, Mohammed Abdel Hady
et al.
Extraction with supercritical fluid technique has proved to be effective in many applications including extraction and separation of various active principals from medicinal plants. It was used due to its advantages especially safety, specificity, selectivity and ease of component recovery.Ammi visnaga, L. belongs to the family Apiaceae. The fruits are used specifically for the treatment of kidney stones depending on its γ-Pyrones (mainly khellin and visnagin) [2]. The supercritical fluid extraction technique of khellin and visnagin was investigated and the operating conditions for their extraction were optimized. The effect of different pressure (150, 200, 300, 400 and 500 bars), temperature (35, 40, 45, 50 and 55 °C), and particle sizes of the raw material (0.5, 1, 1.4 mm and entire fruits) on the extract yield was studied under dynamic conditions for extraction for a run time of 90 min. Optimum supercritical extraction condition was found to be 200 bars at 45 °C and optimum particle size was found to be 1.4 mm. The yield is yellowish white bitter powder and measures 1.74% w/w relative to the dried weight of the fruits containing 38.414% w/w average γ-Pyrones content of which 29.4%w/w khellin, and 9.014%w/w visnagin.The obtained extracts were analyzed by reversed phase HPLC. Keywords: Ammi visnaga fruits, γ-Pyrones (khellin and visnagin), Supercritical fluid extraction and HPLC
Therapeutics. Pharmacology, Pharmacy and materia medica
Abdul Karim F. Jumaa, Alaa A.Abdulrasool, Hikmet A.Al – Dujali
Orphenadrine is an anticholinergic ,antimuscarinic , centrally acting skeletal muscle relaxant .It presents in the form of citrate and HCl salts which are used in treatment of the symptoms of mild Parkinson's disease and also it is used as adjuvant with other drugs in the therapy .
Many trials were made to formulate Orphenadrine citrate as a plain tablet using wet granulation or direct compression technique in order to get a satisfactory formula through studying the effect of various factors such as binders , diluents and disintegrants types .
The best formula was obtained by using Poly Vinyl Pyrolidine (PVP) as a binder also the results indicated that starch and mannitol gave acceptable physical properties to the tablets when they were used as diluents . At the same time , the results showed that Avicel which was used as a disintegrant gave an acceptable disintegration and dissolution time in comparison with the reference tablet DISIPAL Ò. In addition , the selected formula was used to study the effect of method of incorporation of disintegrant on the physical properties of tablets .It was found that the intragranular incorporation resulted in a shorter disintegration and dissolution times .The stability of Orphenadrine citrate prepared tablets was also studied upon storage at 50°C, 60°C and 70°C for four months .The drug was fairly stable and the expiration date for the prepared tablet was considered to be equal for 5 years .On the other hand , the results of clinical study on patients suffering from Parkinson's disease indicated that patients with tremor (regular rhythmic oscillation of extremities especially hand and finger ) and mild symptoms of Parkinson's disease showed a good response to the prepared tablets , but it had no effect on patients of dystonia ( fixed upward gaze , neck twisting ,clenching jaws ) and akinesia ( slow down of movement of voluntary muscle and difficulty of initiation of movement ).
The overall results of this study indicate that the drug can be prepared as tablets , which fit the requirements of British Pharmacopoeia since the prepared tablets gave satisfactory results .
RESUMO Dimorphandra mollis Benth. (Leguminosae-Caesalpinioideae) é uma espécie arbórea, encontrada no bioma Cerrado, utilizada na recuperação de áreas degradadas e na ornamentação. Dos frutos, extrai-se a rutina, um bioflavonoide utilizado na indústria farmacêutica, o qual atua na permeabilidade e na resistência dos vasos capilares. Esta pesquisa teve como objetivo verificar os efeitos do tipo de solo e de adubos sobre a emergência e o vigor da fava-d’anta semeada diretamente no campo. O delineamento experimental adotado foi em blocos ao acaso, em esquema fatorial 4 x 2 (quatro tipos de adubação e dois tipos de solo), com sete repetições de cinco sementes cada. Foram avaliadas as seguintes características: emergência, primeira contagem da emergência, índice de velocidade de emergência, altura e diâmetro da plântula. Não houve interação significativa entre os fatores, tipo de solo e adubos. Os melhores resultados para emergência e IVE são obtidos quando a semeadura é realizada em solo local.
Fatemeh Soleymani, Nikinaz Ashrafi, Arash Tehrani-banihashemi
et al.
Background: Elderly are prone to many acute and chronic age-related diseases, which needed multiple medicine usage. Therefore, evaluation of medicine use pattern in this group is very important and a significant issue in public health system policy.
Methods: This study was a cross-sectional household survey conducted in 20 clusters of Tehran. Each cluster consists of 40 households who had at least one person over the 60 years old. Different medicine items used by the individuals over 60 years old were asked and recorded by the interviewers.
Results: A total of 1054 men and women over 60 years old were enrolled to the study. About 49.4% were male and 50.6% were female. About 69% of the study population used at least one medicine per day regularly, and 46.2% used to consume medicines as self-medication. Mean items per prescription were 3.57 for patients who used medicines regularly every day. The most frequent medicines used in this group were cardiovascular (68.6%) and central nervous system medicines (61.7%). Aspirin 80 mg, atenolol, and calcium-D were the most frequent medicines used regularly, but not daily. Acetaminophen 325 mg and acetaminophen codeine were the most frequent self-medications.
Conclusion: Since elderly people may have multiple comorbidities, which require poly-pharmacy use. Also, due to the high prevalence of drug use without prescription among this group of people, which was about 46% in our study, it is crucial that physicians and other health care providers consider the risk of adverse drug reactions and drug interactions in each visit of the patient.
Sônia Regina Marangoni, Magda Lúcia Félix Oliveira
This study characterized the sociodemographic and obstetric profile of women users of drugs of abuse during pregnancy. This is a descriptive and exploratory study, whose approach technique was the document records analysis of toxicological occurrence and medical charts of 32 women referred to a center for information and toxicological assistance of the Paraná State, between 2008 and 2010. The data were subjected to descriptive statistics. Most women had between 15 and 24 years (59.4%), between the first and third gestation, without prenatal care, poorly educated, without paid occupation (93.8%), and were in a common-law marriage (50%). Tobacco was used by 27 women (84.4%), crack by 24 (75%), and alcohol by 23 (71.7%). Besides the habitual use of drugs of abuse, it also stood out as risk factors before the pregnancy: teenage pregnancy, insecure marital status, and low education. As for the risks during the pregnancy, the most important clinical and obstetric problems were associated with addictive behavior. The sociodemographic profile corroborated the literature, but the multiparity, the low adhrence to the prenatal care, the multiuse of drugs, and the high number of complications, have indicated problems of health services to reach these women, resulting in a prolonged stay length, increased use of neonatal beds, and neonatal death.