Volume 1, Number 1, 2022
5-Fluorouracil Ameliorates the Hematotoxicity Induced by Cyclophosphamide in Male Albino Rats
Abstract
Background: Cyclophosphamide (CPA) is a drug with a wide spectrum of clinical uses. Its effectiveness in the treatment of cancer (acute and chronic leukemias, lymphoma, and multiple myeloma) and non-malignant diseases such as rheumatoid arthritis and vasculitis has been well established. Objectives: The present investigation aimed to study the effect
[...] Read more.
Background: Cyclophosphamide (CPA) is a drug with a wide spectrum of clinical uses. Its effectiveness in the treatment of cancer (acute and chronic leukemias, lymphoma, and multiple myeloma) and non-malignant diseases such as rheumatoid arthritis and vasculitis has been well established. Objectives: The present investigation aimed to study the effect of a sub-lethal dose of the cyclophosphamide, 5-FU combination of 5-FU, and CPA on haematological parameters in the albino rats. Materials and Methods: Twenty-eight male adults were grouped randomly into four groups (n=5 in each group). Group I (control): Rats were injected with saline intraperitoneally at a dose of 1.0 ml/kg b.w. for 14 days. Group II cyclophosphamide (CPA): Cyclophosphamide at a dose of 10 mg/kg day by day through i.p. to rats for 14 days. Group III Fluorouracil (5-FU): 5-Fluorouracil at a dose of 10 mg/kg day by day in saline was given through i.p. to rats for 14 days. Group IV (CPA+5-FU): Rats were given CPA followed by 5-FU at a dose of 10 mg/kg per day (day by day) through i.p. to rats for 14 days. At the end of the experimental period, rats were anesthetized using light ether. Blood samples were taken for hematological evaluation. Results: White blood cells, hemoglobin content and red blood cell counts were significantly decline in rats treated with individual treatment with CPA and 5-FU in comparison to the control group, while the Combination antagonize the changes produced by CPA in hemoglobin and red blood cell counts. Intraperitoneal individual treatment with CPA and 5-FU in rats caused a significant reduction in the hematocrit and platelet. The reductions in these measured hematological parameters were also significantly and slightly ameliorated when the animals were given a combination of CPA and 5-FU. Cyclophosphamide and 5-FU individually reduced lymphocytes, neutrophils, eosinophils, and monocytes; while the combination of CPA and 5-FU antagonized these changes compared to CPA treated group. Conclusion: It could be concluded that the treatment of mammals with chemotherapy is associated with the production of free radicals that lead to hazardous alterations in hematological parameters. However, 5-FU and CPA combination could produce a significant amelioration in most cases for these changes. Future work should consider combined chemotherapy regimens, as two or more mechanisms of action of chemotherapeutic drugs could be more powerful than one mechanism. Using cyclophosphamide and 5-fluorouracil in combination may reduce cyclophosphamide’s side effects when given individually.Full article
Figures
Article
Extended Rule of Five and Prediction of Biological Activity of Peptidic HIV-1-PR Inhibitors
Abstract
In this research work, we have applied “Lipinski’s RO5” for pharmacokinetics (PK) study and to predict the activity of peptidic HIV-1 protease inhibitors. Peptidic HIV-1-PRIs have been taken from literature with their observed biological activities (OBAs) in term of IC50. The logarithms of the inverse of IC50 have been used
[...] Read more.
In this research work, we have applied “Lipinski’s RO5” for pharmacokinetics (PK) study and to predict the activity of peptidic HIV-1 protease inhibitors. Peptidic HIV-1-PRIs have been taken from literature with their observed biological activities (OBAs) in term of IC50. The logarithms of the inverse of IC50 have been used as biological end point o(log1/C) in the study. For calculation of physicochemical parameters, the molecular modeling and geometry optimization of all the derivatives have been carried out with CAChe Pro software using semiempirical PM3 method. Prediction of the biological activity of the inhibitors has shown that the best QSAR model is constructed from pharmacokinetic properties, molecular weight and hydrogen bond acceptor. This also proved that these properties play important role to describe the PKs of the drugs. On the basis of the derived models one can build up a theoretical basis to access the biological activity of the compounds of the same series.Full article
Figures
Article
Nicotinic agonists promoted the activation of nicotinic acetylcholine a7 receptors (a7 nAChR) in neurons, but failed to activate these receptors in mouse peritoneal macrophages.
Abstract
Nicotinic acetylcholine receptor (nAChR) of subtypes said "neuronal" are expressed in epithelial and immune system cells and participate in acetylcholine signaling by neural or non-neural pathways. It has been shown in macrophages that activation of type α7 nAChRs inhibits the release of pro-inflammatory cytokines, but the ion channel function has
[...] Read more.
Nicotinic acetylcholine receptor (nAChR) of subtypes said "neuronal" are expressed in epithelial and immune system cells and participate in acetylcholine signaling by neural or non-neural pathways. It has been shown in macrophages that activation of type α7 nAChRs inhibits the release of pro-inflammatory cytokines, but the ion channel function has not been recorded in these cells. The objective of this work was to clarify what are the molecular mechanisms of transduction of α7 nAChRs in macrophages. To this end, RAW 264.7 cells, mouse peritoneal macrophages and rat hippocampal neurons were used. Cells were submitted to electrophysiological studies and stimulated with brief applications of the agonists acetylcholine, choline and nicotine, associated or not with the allosteric modulator PNU-120596. Responses to ATP were recorded as a reference. Furthermore, macrophages were submitted to cytokine quantitation. The electrophysiological results showed that macrophages responded to ATP but did not show whole-cell current by stimulation with nicotinic agonists. However, hippocampal neurons stimulated in the same pharmacological conditions of the macrophages showed ionic currents typical of the α7 nicotinic receptors. No effect of nicotine was observed in the lipopolysaccharide-induced TNF-α release. These results suggest that the α7 nAChR in macrophages do not work as ion channels similar to those expressed in neurons.Full article
Figures
Article
Blockchain Technology – A Algorithm for Drug Serialization
Abstract
The Blockchain technology uses different type of database that transact data in blocks and then chained each data blocks. When data fills one block, it is chained the same data onto previous block therefore, all the data blocks are stored in chronological order. The blockchain technology can help to ensure
[...] Read more.
The Blockchain technology uses different type of database that transact data in blocks and then chained each data blocks. When data fills one block, it is chained the same data onto previous block therefore, all the data blocks are stored in chronological order. The blockchain technology can help to ensure that data in supply chain is reliable, accurate and can be shared with all stakeholders without any manipulation. It makes supply chain more transparent and end-to-end digital visibility of data source. Blockchain is stringent technology which fill the gap between stakeholders by providing transparent unmanipulated and truthful data in supply chain. There are many initiatives has been taken by multiple regulatory bodies with partnering with supply chain stakeholders including pharmaceutical manufacturer, distributors and dispensers. In USA, Food and Drug Administration’s regulatory body Drug Supply Chain Security Act (DSCSA) initi-ated pilot program in 2019 with the partnership of leading pharmaceuticals distributors to au-thenticating saleable returns to distributor from supply chain partners. DSCSA used MediLedger blockchain interoperable technology for process evaluation and it robustness for mitigating risk of drug counterfeiting possibilities in supply chain. The DSCSA found that pilot project was suc-cessful and results were astonishing. Later it was declared that blockchain technology can also be used for meeting DSCSA’s 2023 Act for unit level traceability.Full article
Figures
Review Article
Dynamics of Pharmaceutical Drugs Serialization
Abstract
The healthcare access is fundamental rights for every human being. It is Governments responsibility to provide good healthcare services and infrastructure to its citizen. Since last few decades, Government and healthcare industries are struggling to minimize the adverse events impacting people health due to fake medicine. The world health organization
[...] Read more.
The healthcare access is fundamental rights for every human being. It is Governments responsibility to provide good healthcare services and infrastructure to its citizen. Since last few decades, Government and healthcare industries are struggling to minimize the adverse events impacting people health due to fake medicine. The world health organization also predicted that 4 out of 10 medicines in developing and poor countries are either fake or potentially adulterated. Counterfeit drugs cost billions of dollars deficit to world economy and reduce research and development (R&D) funds allocation from organizations. Stopping counterfeit medicine into supply chain is main challenge for Government and regulatory authorities. The Government and regulatory authorities are now making stringent guidelines to prohibit criminals and counterfeiters to supply fake medicine in markets. Healthcare industry need stringent regulations and secure technologies provide sage and authentic drugs to patients. The FDA has published the 10 years roadmap to implement the drug traceability in United States. The Healthcare Distribution Alliance (HDA) has also mandated to print several barcodes and human readable data in product packaging hierarchy. The FDA is participating in pilot project with leading pharmaceutical drug manufacturer and wholesales to use blockchain technology in interoperable digital network for securing digital traceability data transfer between authorized trading partners.Full article
Review Article
The Clinical use of Guidelines for the Pharmacological Treat-ment of All Diseases is Problematic Because of Little Information about Adverse Effects
Abstract
In a guideline for the pharmacological treatment, the priority is usually based on the strength of the evidence of efficacy. This is academically correct, but not clinically appropriate. Adverse effects are as important as efficacy in clinical practice. There are guidelines for the pharmacological treatment that take adverse effects into
[...] Read more.
In a guideline for the pharmacological treatment, the priority is usually based on the strength of the evidence of efficacy. This is academically correct, but not clinically appropriate. Adverse effects are as important as efficacy in clinical practice. There are guidelines for the pharmacological treatment that take adverse effects into account. However, most adverse effects considered are those obtained in double-blind studies of pharmacological treatment performed to prove efficacy. In the treatment guidelines of various diseases, too little effort is spent on pharmacological adverse effects compared to the effort spent on pharmacological efficacy. I would like to make recommendations in the guidelines for the pharmacological treatment of all diseases. The guidelines for the pharmacological treatment of various diseases should be developed with increased efforts to investigate adverse effects. Some guidelines for the pharmacological treatment use systematic reviews and meta-analyses to examine the efficacy of medicine, and similar methods should be used to examine the adverse effects of medicine. It is easy to prioritize medicines based on evidence of efficacy. However, it is not appropriate to prioritize medicines in clinical practice based solely on evidence of efficacy. Adverse effects should also be considered in priority ranking of medicine in clinical practice. In addition to efficacy and adverse effects, price and the degree of off-label prescribing also affect the priority ranking of medicine in clinical practice.Full article
Opinion
ISSN: 2834-5436
DOI prefix: 10.31586/ujpp
Journal metrics
Publication year
2021-2025
Journal (home page) visits
36595
Article views
15993
Article downloads
3176
Downloads/article
151.24
APC
99.00