Current Drug Therapy - Volume 17, Issue 3, 2022

Background: Dermatomycosis is a type of fungal infection that can infect human skin, hair, and nails; an increasing growth of fungal infections ranging from superficial to systemic infection is alarming. Common causative agents are Candida, Cryptococcus, Aspergillus, and Pneumocystis species. A wide range of antifungal drugs is used for the treatment of mycotic infections. These antifungal drugs can be oral or topical. The topical therapy ensures reduced side effects. Some act as fungistatic, while others act as fungicidal. These drugs work by a different mechanism of action to prevent and cure fungal infections. Objective: The effective treatment of the fungal infection includ the use of proper antifungal drug therapy. Antifungal drugs are classified into various classes. This paper focuses on understanding and interpreting the detailed molecular and cellular mechanism of action of various classes of anti-fungal drugs with their important characteristics along with the safety and efficacy data of individual drugs of the particular class. Methods: The data selection for carrying out the respective study has been made by studying the combination of review articles and research papers from different databases, like ResearchGate, PubMed, MDPI, Elsevier, ScienceDirect, and MedCrave, ranging from the year 1972 to 2019, by using the keywords like “anti-fungal agents”, “dermatophytes”, “cutaneous candidiasis”, “superficial fungal infections”, “oral candidiasis”, “amphotericin”, “echinocandins”, “azoles”, “polyenes” “ketoconazole”, “terbinafine”, “griseofulvin”, “azoles”. Result: Based on interpretation, it is concluded that the different classes of antifungal drugs follow the different mechanisms of action and target the fungal cell membrane, and are efficient in reducing fungal disease by their respective mechanism. Conclusion: The prevention and cure of fungal infections can be done by oral or topical antifungal drugs aimed to destroy the fungal cell membrane. These drugs show action by their respective pathways that are either preventing the formation of ergosterol or squalene or act by inhibiting the β-1,3- glucan synthase enzyme. All the drugs are found to be effective in treating fungal infections.

Proteoglycans are essential biomacromolecules that participate in matrix structure and organization, cell proliferation and migration, and cell surface signal transduction. However, their roles in physiology, particularly in CNS, remain incompletely deciphered. Numerous studies highlight the elevated levels of chondroitin sulphate proteoglycans (CSPGs) in various diseases, like cancers, and neurological disorders, like spinal cord injury (SCI), traumatic brain damage, neurodegenerative diseases, and are mainly implicated to hinder tissue repair. In such a context, chondroitinase ABC (ChABC), a therapeutic enzyme, has shown immense hope to treat these diseases in several preclinical studies, primarily attributed to the digestion of the side chains of the proteoglycan chondroitin sulphate (CS) molecule. Despite extensive research, the progress in evolution of the concept of therapeutic targeting of proteoglycans is still in its infancy. This review thus provides fresh insights into the emerging therapeutic applications of ChABC in various diseases apart from SCI and the underlying mechanisms.

Background: Premedication is used prior to surgery to reduce the adverse effects that might result from general anesthesia. Objective: This study was performed to examine the types and utility of various pre-anesthetic agents in 100 patients aged between 3 and 60 years who were admitted to Baladrooz General Hospital for different surgical operations during February (winter) and April (spring) 2021. Methods: A total of 62 patients received isoflurane, and 7 patients received sevoflurane, both by inhalational administration. The other 31 subjects were administered Marcaine (bupivacaine) by spinal anesthesia. Results: In this study, eight types of pre-anesthetic medication were administered prior to anesthesia, as follows: hydrocortisone (35 patients), metoclopramide (25 patients), atropine (13 patients), dexamethasone (12 patients), midazolam (7 patients), morphine (3 patients), ephedrine (3 patients), and fentanyl (2 patients). The most commonly used pre-anesthetic agent administered with isoflurane was hydrocortisone (37 patients), while the least used were fentanyl and morphine, which were administered to 3 patients each. Hydrocortisone was the premedication most often used (6 patients) with isoflurane, followed by dexamethasone, midazolam, and metoclopramide (5, 2, and 2 patients, respectively). The preanesthetic agent used most often with sevoflurane was hydrocortisone (6 patients), followed by dexamethasone (5 patients) and metoclopramide and midazolam (2 patients each). The premedication most commonly used with bupivacaine was metoclopramide (25 patients), while the least used was midazolam (2 patients). Conclusion: The study showed that several different pre-anesthetic drugs were used prior to anesthetic agents, which suggests that the selection of a pre-anesthetic drug depends on the risks that might be incurred when using a specific anesthetic drug.

Background: Persistent hyperglycemia in diabetes mellitus (DM) is considered the leading cause of morbidity and mortality associated with both microvascular and macrovascular complications, having a greater economic impact. This study aimed to assess the impact of socioeconomic status, prescribing patterns, and patient compliance in type 2 diabetes mellitus patients. Methods: This study was carried out at the Department of Medicine and Diabetic Clinic of Hakeem Abdul Hameed (HAH) Centenary Hospital at Hamdard University, New Delhi, India. We conducted a prospective observational study on prescribing patterns and monitoring adverse drug reactions (ADRs) in patients with type 2 DM (T2DM) under standard care. We enrolled 150 confirmed cases, and data was obtained from pre-validated questionnaires and then coded and analyzed to observe the association between variables. Results: The glycosylated haemoglobin level in 56% of the cases was between 6.4 to 8.0, and cardiovascular complications were observed as the major comorbidities. 45.33 % of the cases were on mono drug therapy, and metformin (23. 52 %) was the drug of choice, followed by glimepiride (23.52 %). Among the dual drug therapies, sitagliptin with metformin and triple-drug therapy, glimepiride concurrent with metformin and voglibose was the most preferred drug in the treatment of T2DM. Sitagliptin was observed to be a major patient burden (46.213 USD). In only 7.33 % of the cases, we observed definite ADR in T2DM patients. Underprivileged awareness, mainly due to low literacy, was a major concern in the development of new cases of T2DM. Conclusion: We observed better patient compliance; however, a disease awareness program must be implemented. The use of oral hypoglycaemic drugs is still dominant in clinical practice and cardiovascular disorders as comorbidities emerge as a greater challenge in terms of patient outcome and cost burden.

Background: Fertility control becomes necessary for under-developed and developing nations for the betterment of the economy, environment, and society. Plant Plumeria acuminata, “Temple tree or Frangipani,” of the Apocynaceae family, has exhibited several activities similar to contraceptive medicine and is widely distributed in India. Objective: Present investigation aimed to study the anti-ovulatory and anti-implantation activities of ethanolic extract from P. acuminata leaves and roots in Wistar rats. Methods: Ethanolic extracts of P. acuminata leaves and roots were subjected to qualitative phytochemical analysis and acute toxicity test. Immature female rats were used to explore anti-ovulatory characteristics by administering HCG as a standard ovulation-inducing drug. Mated females were used for exploring anti-implantation characteristics. Levonorgestrel and Ethinylestradiol were administered as standard anti-implantation drugs. Morphological, hematological, hormonal, and histological examinations were performed. Results: LD50 value, i.e., 2000 mg/kg from acute toxicity test, resulted in the selection of 100, 200, and 400 mg/kg dose values for both leaf and root extracts. Treatment with these brought ∼2-54%, ∼5- 48%, and ∼1-68% changes respectively in the hormonal, growth factors’ and cytokines’ profiles. Ovarian histology revealed restricted follicle maturation and ovulation, whereas uterine histology unveiled a ∼5-28% decrease in the endometrium thickness, making it unreceptive for implantation after treatment with PAL and PAR extracts. Conclusion: Anti-ovulatory and anti-implantation results obtained here can be attributed to the presence of plumericin, sterol, as well as triterpene groups of phytochemicals from ethanolic extracts of leaves and roots, making them potent contestants for studies on future contraceptive medicines.

Introduction: Zanthoxylum rhetsa fruits, a common spice in many cuisines, have proven to have a good therapeutic potential and are routinely used in food, medicine, and commerce. The present study was conducted to screen the in vitro antileukemic and antimalarial activities of the methanolic extract of Z. rhetsa fruits and conduct mechanistic studies for antileukemic activity. Methods: Methanol extract was prepared by maceration process and standardised with lupeol as a marker using HPLC. MTT and SRB assays were used to establish the cytotoxicity of the extract against L929 and leukemic cell lines (Jurkat, K562, and HL-60). The amount of ROS in cell lines was detected by flow cytometry using 2',7'-dichlorodihydrofluorescin diacetate. Apoptosis on HL-60 was detected by Annexin-V/PI dual staining assay through cell cycle analysis and gel electrophoresis. In vitro antimalarial activity was conducted on Plasmodium falciparum CQ sensitive 3D7 strains according to the WHO 2001 guidelines. Results: The methanol extract contained 1.03% of lupeol. Potent antileukemic activity (IC50 <10 μg/mL) was observed against HL-60 in comparison to K562 and Jurkat cell lines. The extract induced apoptosis in cancer cells in the proliferative and mitotic phase without DNA fragmentation. Therefore, the antileukemic activity exhibited by the extract could be attributed to the increased oxidative stress generated in cancer cells. Fruits also exhibited good antioxidant activity against normal cells, thus proving beneficial as cytoprotective agents. Promising antimalarial activity (IC50 = 16.21 μg/mL) with high selectivity against malarial parasites was exhibited by the fruits. Conclusion: Thus, the fruits of Z.rhetsa can be used as an adjuvant therapy to reduce the side effects and resistance associated with chemotherapy and can be a potential candidate for drug discovery research in the areas of cancer and parasitic infection.

Background: Diabetes mellitus is a metabolic disorder that has become a major health issue in the modern era due to long-term health consequences. α-amylase and α-glucosidase are the key enzymes involved in the digestion of starchy foods, and the inhibition of these enzymes is regarded as a postprandial hyperglycemia control strategy. Objective: The primary goal of this work is to examine the antioxidant activity as well as α- glucosidase inhibitory activity of Polygonatum verticillatum rhizomes via in vitro test. Methods: The in vitro α-glucosidase inhibition activity was performed using p-nitrophenyl-α- Dglucopyranoside (PNPG) substrate. 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay was performed to estimate the antioxidant activity. Results: The in vitro α-glucosidase inhibitory activity of Polygonatum verticillatum was investigated for the very first time. Of the three fractions and a crude extract, the ethyl acetate (EA) fraction disclosed potent inhibition activity against α-glucosidase enzyme with an IC50 value of 22.3 ± 0.1 μg/mL. Likewise, the IC50 values for dichloromethane (DCM) fraction and the crude extract against α- glucosidase were reported at 34 ± 0.1 μg/mL and 402.2 ± 0.2 μg/mL, respectively. Similarly, the EA fraction, crude extract, and DCM fraction disclosed promising antioxidant activity with IC50 = 55 ± 0.3 μg/mL, 171.5 ± 0.6 μg/mL, and 164.1 ± 3.4 μg/mL, respectively. Conclusion: These findings concluded that among the crude extract and fractions of Polygonatum verticillatum of Nepalese origin, the EA fraction constituted a potent α-glucosidase inhibiting and antioxidant agent. Further research is required to expose the inhibiting compounds.