Effects Of Conventional Drugs Research Articles

Investigation of Antibiofilm and Antibacterial Properties of Green Synthesized Silver Nanoparticles from Aqueous Extract of Rumex sp.

The decrease in the effectiveness of conventional drugs as a result of the growth of resistance to antibiotics has increased the need for innovative tools to control the infections. At this point, metallic nanoparticles, in particular silver nanoparticles, have appeared as a promising method. In the current study, the extract of Rumex sp. (Labada, dock) leaves was used as a reducing agent for the formation of silver nanoparticles. Unlike similar studies, in this study the synthesis conditions were optimized by changing the extract ratio and silver nitrate concentration. Morphological investigations of synthesized silver nanoparticles showed that spherical homogeneous particles at size under 100nm had been produced. SEM/EDS and FTIR analyses showed that plant components are involved in the synthesis of nanoparticles. It was also determined that higher extract ratio reduced nanoparticle size. The antimicrobial effects of the synthesized nanoparticles against Gram-positive and Gram-negative bacteria were tested, and it was determined that all nanoparticles exhibited activity against both groups. Rumex sp. silver nanoparticles (NPs) were revealed to exhibit antibiofilm activity against three different isolates with moderate and strong biofilm-forming ability. The NPs reduced the biofilm-forming capacity of Acinetobacter baumannii and Klebsiella pneumonaie by 2.66-fold and 3.25-fold, whereas they decreased the Escherichia coli biofilm-forming capacity by 1.25-fold. The investigation of microbial biofilm could play an important role in developing new strategies for treatment options. Our results suggest that Rumex sp. silver NPs may have a high potential for use in the treatment of pathogenic strains.

Efficacy of coronavirus disease 2019 vaccines in patients with rheumatic diseases.

In this study, we report the immune response to the BNT162b2 vaccine and CoronaVac vaccine after a two-dose vaccination and the effects of conventional drugs, immunosuppressive drugs, and new-generation therapies on vaccine responses in patients with rheumatic and musculoskeletal diseases (RMDs). This is a prospective observational study conducted with 94 patients (65 males, 29 females; mean age: 42.7±12.1 years; range, 19 to 69 years) between May 2021 and January 2022. The immunogenicity of the two-dose regimens of the BNT162b2 and CoronaVac vaccines in adult patients with RMD was analyzed according to disease and treatments. Serum immunoglobulin G antibody levels against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) spike proteins were measured four weeks after the second dose of vaccines. Patients on regimens including mycophenolate, rituximab, and steroids were less likely to develop an antibody response (p=0.001, p=0.06, and p=0.001, respectively). Impairment of vaccine response by other conventional disease-modifying antirheumatic drugs and by anti-tumor necrosis factor treatments was not shown. Younger participants appeared more likely to develop an antibody response. The CoronaVac vaccine was less likely to develop an antibody response compared to the BNT162b2 vaccine (p=0.002). Systemic lupus erythematosus and vasculitis had the lowest antibody titers compared to other RMDs. Patients receiving mycophenolate mofetil, rituximab, and steroids should be warned about the risk of a suboptimal vaccine response. If possible, vaccination strategies should be changed, and the dose modification of drugs should be made during the vaccination. Further studies are required to determine the responses to SARS-CoV-2 vaccination and optimization of vaccine response in patients with RMDs.

SOSIALISASI PENGGUNAAN LEAFLET DALAM PENINGKATAN PEMAHAMAN PENGGUNAAN OBAT HERBAL UNTUK PENYAKIT KRONIS DI KOTA DENPASAR

The instability between the success and failure of herbal treatment for chronic diseases illustrates the lack of understanding in society. For this reason, it is necessary to provide socialization of knowledge about herbal medicines through leaflets that are practical, simple, and easy to accept. This activity targets the people of Denpasar City who suffer from chronic diseases and use herbal medicines. The method used is in discussions with respondents who have or are currently undergoing degenerative disease therapy by utilizing herbal medicines as therapy and distributing leaflets containing information on herbal medicines to respondents who are less precise in understanding herbal medicines. The results of community service, giving handouts to the community, can increase knowledge about herbal treatments for chronic diseases. The use of leaflets can increase understanding of herbal medicines about the content, seek information from doctors/pharmacists as a complementary therapy, and different effects of conventional drugs. Thus, leaflets are essential to increase the rational use of medicines, especially herbal medicines.

Enhanced Extraction and Improved Anticancer Activity of Neem (Azadirachta indica) Leaves by Electroporation Technique

Plant-based medicines have been a part of primary healthcare since time immemorial. Natural products have received increasing attention to treat several regenerative diseases due to their availability and fewer side effects than conventional drugs. Towards this, Neem, commonly known as ‘Divine Life-giving tree’, has been investigated for its efficiency against MCF7, breast cancer cell lines. Ethanolic neem extracts were analysed for qualitative phytochemical screening tests, spectral analysis, antioxidant activity, and total phenol contents. In addition, to enhance the recovery of secondary metabolites from the plant extracts, electroporation (EP) technique is used. The effect of EP was studied by comparing with untreated extracts, which exhibits antioxidant activity (∼96% increase) and total phenol contents (∼12.51% increase) than untreated extracts. This indicates that electroporated extract (EE) exhibited higher antioxidant and phenolic activity than other extracts. Furthermore, different concentrations of untreated and electroporated neem extracts were used to study the anti-cancer activity. To enhance the uptake of extracts against cell membranes, electrical pulses of EP1 = 1200 V/cm, 100 s, 8 pulses and, EP2 = 500 V/cm, 20 ms, 8 pulses were used. The results indicate cell viabilities of 35% with untreated extract only, 5.6% with EE, 3.17%, and 2.49% with EP1 + EE extract and EP2 + EE extract, respectively, indicating the potential of the synergy of electrical pulses + EE. The viabilities were lowered by 5–6 times after 72 h. This treatment is more appropriate to achieve maximum cell death, thereby reducing the side effects of conventional drugs in treating breast cancer.

A Diels-Alder polymer platform for thermally enhanced drug release toward efficient local cancer chemotherapy

ABSTRACT We reports a novel thermally enhanced drug release system synthesized via a dynamic Diels-Alder (DA) reaction to develop chemotherapy for pancreatic cancer. The anticancer prodrug was designed by tethering gemcitabine (GEM) to poly(furfuryl methacrylate) (PFMA) via N-(3-maleimidopropionyloxy)succinimide as a linker by DA reaction (PFMA-L-GEM). The conversion rate of the DA reaction was found to be approximately 60% at room temperature for 120 h. The reversible deconstruction of the DA covalent bond in retro Diels-Alder (rDA) reaction was confirmed by proton nuclear magnetic resonance, and the reaction was significantly accelerated at 90 °C. A PFMA-LGEM film containing magnetic nanoparticles (MNPs) was prepared for thermally enhanced release of the drug via the rDA reaction. Drug release was initiated by heating MNPs by alternating magnetic field. This enables local heating within the film above the rDA reaction temperature while maintaining a constant surrounding medium temperature. The MNPs/PFMA-L-GEM film decreased the viability of pancreatic cancer cells by 49% over 24 h. Our results suggest that DA/rDA-based thermally enhanced drug release systems can serve as a local drug release platform and deliver the target drug within locally heated tissue, thereby improving the therapeutic efficiency and overcoming the side effects of conventional drugs used to treat pancreatic cancer.

Sinapic Acid Loaded Secondary Growth of SiO2–Au Core Shell Nanostructure as an Effective Antiarthritic Agent to Treat Collagen-Induced Arthritis

Systemic autoimmune disease of rheumatoid arthritis (RA) is a severe case of joint deformity. Serious off-targeted drugs are not capable of curing RA and lead to increased risk of infection. Nanoparticles-based arthritis therapy is a promising approach to promote effective treatment strategy in inflammatory tissues. In particular, an inorganic-metal hybrid form of core–shell nanostructure has a significant role in the drug application due to its unique properties arising from either core or shell materials. Presently, the Au–SiO2 core–shell nanomaterials with an average diameter of 78 nm were successfully synthesized. The nanomaterials revealed a very high sinapic acid (SA) loading to eliminate the inflammatory response in RA by avoiding the side effects of conventional drugs. Various characterization techniques revealed that the as-fabricated Au–SiO2 has a higher-contrast core and aggregates of SiO2 on their surfaces/of the shell. Besides, Au–SiO2 core–shell exhibits the large extended pore structure to store a large quantity of SA drugs. Then, the mice were treated with different doses of SA loaded Au–SiO2 core–shell to assess the various biochemical parameters, including body weight, arthritic score analysis, hind paw volume, organ indices measurement, histological analysis pro-inflammatory cytokines, and anti-serum antibody analysis. The obtained results have proven that SiO2–Au develop a core–shell skin structure and each with its unique SA loading might act as a potential anti-inflammatory agent, which can be effectively used to treat collagen-induced arthritis compared to Au–SiO2 and SA. Therefore, SA loaded Au–SiO2 core–shell nanomaterials might employ as an interesting candidate in future arthritis applications.

The effects of conventional drugs in the treatment of rheumatoid arthritis on the serum lipids.

Background:Rheumatoid arthritis (RA) is a common chronic autoimmune disorder that leads to damage of human joints. There are various treatment approaches in which different drugs are prescribed which have several alterations in serum lipids. This research aimed to study the effect of RA treatments on the serum lipids.Materials and Methods:Two hundred randomly selected patients with RA were randomly assigned to three different groups. The first group of patients was treated with a combination of prednisolone (PRD) and hydroxychloroquine (HCQ). The second group was treated with three drugs including PRD, HCQ, and methotrexate (MTX). The third group was treated with four medications including PRD, HCQ, MTX, and sulfasalazine. Within each group, the lipid factors such as triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), erythrocyte sedimentation rate, and visual analog scale were measured at the beginning of the experiment and 6 months after exposing the treatments. For each group, we also calculated the Disease Activity Score-28 (DAS-28). The analysis of variance revealed that the overall DAS-28 was significantly different among the three groups.Results:In the first group, the level of TG and TC significantly decreased (P = 0.015 and P ≤ 0.001, respectively). In the second group, the level of TG and LDL significantly decreased (P = 0.009). In the third group, the LDL level increased considerably (P < 0.001). The HDL level significantly increased in all three groups (P = 0.012, P = 0.014, and P = 0.028, respectively).Conclusion:The treatment PRD + HCQ + MTX was more effective in reducing the LDL level and increasing the HDL level. To reduce the risk of cardiovascular diseases in patients with RA, it is important to prescribe the combination of drugs which leads and normalizes the lipid profile levels.

A clerodane diterpene from Polyalthia longifolia as a modifying agent of the resistance of methicillin resistant Staphylococcus aureus

BackgroundStaphylococcus aureus infections are raising serious concern across the world. The effectiveness of conventional drugs is continuously decreasing due to global emergence of multidrug resistance (MDR) and therefore, new resistance-modifying agents (RMAs) are highly needed. HypothesisClerodane diterpene 16α-hydroxycleroda-3,13(14)-Z-dien-15,16-olide (CD) from leaves of Polyalthia longifolia (Sonn.) Thwaites (Annonaceae) as RAM will be useful in improving the current treatment strategies for staphylococcal infections. Study designIn the present study, we determine the resistance-modifying activity of CD using clinical isolates of MRSA. Further, the influence of CD on innate immune response was also evaluated in vitro and in vivo. The nature of potential interactions was determined by fractional inhibitory concentration indices (FICIs) calculated from microdilution assays and time–kill curves. ResultsThe result of in vitro combination study showed that CD significantly reduced MIC of fluoroquinolones up to 16-folds (FICI 0.315-0.500), while in S. aureus infected Swiss albino mice model, combination of CD with norfloxacin, significantly (p<0.01, p<0.001) lowered the systemic microbial burden in blood, liver, kidney, lung and spleen tissues in comparison to CD, norfloxacin alone as well as untreated control. Flow cytometry analysis clearly showed that CD significantly inhibited EtBr efflux and extended post-antibiotic effect. In qRT-PCR analysis, CD alone as well as in combination, significantly modulated the expression of various efflux pump genes including norA up to 2-fold in clinical isolate MRSA-ST2071. Further, the in vitro combination study of the CD (10, 5, 2.5µg/ml) along with the norfloxacin (10µg/ml) depicted a significant decline in the pro-inflammatory cytokines, IL6 and TNF-α. In septic shock mice model, CD did not exhibit any significant changes in the level of pro-inflammatory cytokines. ConclusionThis is the first report on drug resistance-modifying potential of CD through inhibition of MDR efflux pump.

Recombinant trail: a synergistic effect in myeloid leukemias

The tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL/Apo-2L) is a member of the TNF superfamily that trigger and activate 2 death receptors, DR4 and DR5, and 2 decoy receptors, DcR1 and DcR2. Several studies demonstrated that TRAIL in monotherapy can induces cancer cell death cells, but few have been done in leukemias in combination with conventional drugs. The aim of this work is to analyse the potential synergist effect of a recombinant TRAIL (rhTRAIL) in myeloid leukemias. For this, 2 myeloid leukemia cell lines, HL-60 (promyelocitic leukemia) and K-562 (Chronic Myeloid Leukemia) were treated with different concentrations of rhTRAIL as single agent and in combination with ATRA (all-transretinoic acid) and imatinib, respectively. The viability was measure using the trypan blue test and cell death by flow cytometry (FC) and Optical Microscopy. TRAIL and TRAIL-Rs were evaluated by FC. Our results show that rhTRAIL induced a decrease in cell viability inducing cell death, in a time, dose and cell type dependent manner. We observe an IC50 in HL-60 treated for 48h of 250 ng/mL, although in K562 cells, rhTRAIL wasn’t able to induce a significant effect. However, when we previously treated the cells with ATRA or IMATINIB a synergistic effect is observed, mainly in HL60 cells. These results may be correlated with the differential TRAIL receptors expression, namely the presence of the anti-apoptotic TRAIL receptors, in K562 cells. On the other hand, the higher percentage of pro-apoptotic TRAIL receptors may be related with the therapeutic efficacy of rhTRAIL in HL-60 cells. Our study suggests that rhTRAIL can be use as a new therapeutic aproach in APL, as single agent. However, it can potentiate the cytotoxic effect of conventional drugs.

Drug Interaction Studies of Therapeutic Proteins or Monoclonal Antibodies

Drug interactions can alter the pharmacokinetics and/or pharmacodynamics of a drug. In pharmacokinetic drug interactions, the concentrations of 1 or more drugs are altered by another. This change in concentration in a given drug may be due to changes in absorption, distribution, metabolism, or elimination. The pharmacodynamic interaction can lead to additive, synergistic, or antagonistic effects of a drug. Drug interaction studies are regularly conducted with conventional drugs (small molecules), but very few drug interaction studies have been performed with macromolecules (therapeutic proteins or monoclonal antibodies). This is mainly because most macromolecules are not metabolized by the cytochrome P450 system, and their mechanism of elimination is complex. However, it has been shown in several studies that interferons can have an impact on the cytochrome P450 system that may alter the pharmacokinetics and pharmacodynamics of a conventional drug when given with interferons. Therefore, it is important to evaluate the effect of other classes of macromolecules (cytokines, interleukins, monoclonal antibodies) on drug-metabolizing enzymes. It is also imperative that the effects of conventional drugs on the pharmacokinetics and pharmacodynamics of macromolecules be conducted. The present review encompasses several drug interaction studies that were conducted with macromolecules and highlights the impact of these studies on the pharmacokinetics and/or pharmacodynamics of the involved drugs.

Efeito dos anti-inflamatórios não-esteroidais convencionais e seletivos para COX-2 sobre o reparo ósseo

Na presente revisão de literatura foram relacionados trabalhos experimentais e clínicos dos últimos 15 anos referentes aos efeitos dos antiinflamatórios não-esteroidais (AINEs) convencionais e seletivos para COX-2 sobre a formação óssea reparacional. A maioria dos trabalhos mostra que os AINEs convencionais podem atrasar o reparo de fratura de ossos longos e a fusão espinhal, em animais, e interferir negativamente com a taxa de fusão espinhal, em humanos. Apesar da importância comprovada da prostaglandina E2, sintetizada por osteoblastos sob estímulo da enzima ciclooxigenase-2 (COX-2), no controle da formação óssea, os resultados experimentais acerca dos prováveis efeitos inibitórios dos AINEs seletivos sobre o reparo ósseo além de raros são ainda controversos e não há comprovação de que eles interferem com a neoformação óssea reparacional em humanos.

Blockade of the Ras pathway by manumycin, a farnesyltransferase inhibitor, overcomes the resistance of myeloma plasma cells to Fas-induced apoptosis

Ras activation (by point mutation or binding of IL-6) is frequently observed in multiple myeloma (MM). As farnesylation of Ras protein by farnesyltransferase is a critical step for Ras functional activity, farnesyltransferase inhibitors (FTI) have emerged as potential anti-cancer agents. Manumycin, a natural FTI, prevents proliferation and induces apoptosis of myeloma cells refractory to Fasand drug-induced cell death. Fas pathway analysis showed that Fas-resistant apoptosis of Fas-positive myeloma cells parallels FLIP (FLICE/caspase-8-inhibitory protein) expression. Treatment of fresh purified myeloma cells, myeloma cell clone-2 and U266 cell line with manumycin induced down-regulation of FLIP expression with concomitant expression of Apo 2.7 antigen, the marker of early apoptosis. Down-regulation of FLIP mRNA levels in drug-treated cells was associated to suppression of the transcription factor NF-kappaB that plays a central role in chemoresistance, survival and proliferation of myeloma cells. Further analysis showed that manumycin-induced apoptosis involved caspases activation and was prevented by the addition of caspases specific inhibitors. Finally, pretreatment of Fas-resistant/FLIP-positive cells with manumycin sensitised them to Fas-triggered apoptosis. Overall results indicate that manumycin-induced apoptosis involves Fas pathway. FTIs may thus be proposed as a promising class of anti-cancer agents which can boost the cytotoxic effect of conventional drugs by overcoming NF-kappaB activation and Fas-resistant apoptosis.

Novel sensitizing agents: Potential Contribution of COX-2 inhibitor for endocrine therapy of breast cancer

Enhancement of the therapeutic effect of conventional drugs is currently an active treatment strategy for breast cancer, as shown in the clinical application of trastuzumab with chemotherapeutic agents, which prolonged survival even for metastatic disease. Cyclo-oxygenase 2(COX-2)inhibitors, which are chemoprevention agents for familial polyposis coli, are now contributing to this strategy in combination with chemotherapeutic and endocrine drugs. As an endocrine application, overexpression of COX-2 contributes to increased expression of aromatase in the breast tumor. In addition, it is also known to promote rich micro-vessels within the tumor through up-regulation of prostaglandin E2(PGE2), which can induce vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)in cancer cells, and can directly modulate endothelial cell proliferation. Since both rich vasculature and accelerated estrogen synthesis are thought to contribute to unfavorable conditions for the response to endocrine therapy, inhibiting COX-2 with COX-2 inhibitors is a promising strategy to potentiate endocrine therapy.

Diazepam for treating tetanus.

Clinical management of the muscle spasms and rigidity of tetanus poses a difficult therapeutic problem to physicians everywhere, especially in resource poor countries. There are wide variations in therapeutic regimens commonly used in clinical practice due to uncertainties about effectiveness of conventional drugs. Diazepam compared to other drugs (eg phenobarbitone and chlorpromazine) may have advantages because of combined anticonvulsant, muscle relaxant, sedative and anxiolytic effects. To compare diazepam to other drugs in treating the muscle spasms and rigidity of tetanus in children and adults. We searched the Cochrane Neonatal Group trials register (October 2003), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to October 2003), EMBASE (1980 to October 2003), LILACS (2003), CINAHL (October 2003), Science Citation Index, African Index Medicus, conference abstracts and reference lists of articles. We contacted researchers, experts and organizations working in the field and used personal communication. Randomized and quasi-randomized controlled trials. We independently identified eligible trials, assessed trial methodological quality and extracted data. Two studies met the inclusion criteria. Method of generation of allocation sequence, concealment of allocation and blinding were unclear in both studies. A total of 134 children were allocated to three treatment groups comprising diazepam alone, phenobarbitone and chlorpromazine, or phenobarbitone and chlorpromazine and diazepam.Meta-analysis of in-hospital deaths indicates that children treated with diazepam alone had a better chance of survival than those treated with combination of phenobarbitone and chlorpromazine (Relative Risk for death 0.36; 95% confidence interval 0.15 to 0.86; Risk Difference -0.22; 95% CI -0.38 to -0.06). Giving diazepam alone, or supplementing conventional anticonvulsants (phenobarbitone and chlorpromazine) with diazepam, was reported in one study to be associated with a statistically significantly milder clinical course and shorter duration of hospitalization. Although there is evidence that diazepam alone compared with combination of phenobarbitone and chlorpromazine is more effective in treating tetanus, the small size, methodological limitations and lack of data on drug safety from available trials preclude definite conclusions to support change in current clinical practice. The application of the present evidence should be moderated by local needs and circumstances, pending the availability of more evidence. We recommend a large multicenter, randomized controlled trial which compares diazepam alone with combinations of other drugs (excluding diazepam).