Current Drug Therapy - Volume 17, Issue 1, 2022

Background: Peptic ulcer disease (PUD) is prevalent in almost all parts of the world. PUD complications are a major source of health care expenses; however, they are preventable. The major factors responsible for the incidence of PUD and its complication have changed over the past few decades after the identification of non-steroidal inflammatory drugs (NSAIDs) and Helicobacter pylori bacterial infection along with a marked increase in the use of proton-pump inhibitors (PPIs) as drug therapy. The management of PUD has become more complex and challenging due to antimicrobial resistance. Objectives: The objective of the study was to highlight current therapy and novel techniques used in the treatment of peptic ulcer diseases. Methods: An exhaustive literature search has been conducted across PubMed, Google, Scopus and Web of Science electronic databases to extract the crucial information from the relevant literature. Results: In the present review, we have discussed PUD and its pathophysiology. The recent trends in PUD and possible treatments with novel techniques have also been discussed. The type and presence of ulcers cannot be predicted accurately based on symptoms. The available treatment approaches for peptic ulcers based on their clinical presentation and etiology are anti-secretory therapy, endoscopy to reveal ulcers, followed by drug therapy, and triple therapy for H. pylori infection. Conclusion: Thus, the popular and effective methods are very beneficial in controlling PUD. The treatment based on diagnosis is the foremost requirement for ameliorating any disorder. In this article, the emerging techniques and advancements in the treatment and diagnosis of PUD have been reviewed.

Background: Hydatidosis is a parasitic disease caused by the larval stage of Echinococcus granulosus sensu lato. The aim of the current systematic review study was to clarify the effect of garlic on hydatid cyst in vivo and in vitro. Methods: We performed our analyses up to Feb 20, 2021, in accordance with the PRISMA guideline. We systematically searched five English databases (Science Direct, PubMed, Scopus, Ovid and Cochrane) and four Persian databases (Scientific Information Database [SID], Iran Medex, Iran Doc, and Magiran) with appropriate syntax. The data was extracted from the relevant articles and analyzed. Results: From 160 studies obtained by initial search, nine studies were selected for further analysis. Among 6 in vitro studies, 3 (50%) used methanolic extract, 2 (34%) hydroalcoholic and chloroformic extract, and 1 (16%) chloroformic extract. Two (67%) studies used BALB/c mice, and one study (33%) used Swiss albino mice. The method of treatment of mice in all studies was oral. The results showed that garlic has a mild to potent effect on hydatidosis, and this effect was more considerable in vitro than in vivo. Conclusion: Based on the results of various studies, it can be concluded that Allium sativum extract can be used as a suitable alternative to drugs such as albendazole or can be used as a complementary treatment to reduce the dose of the current drugs.

Background: The use of herbal medicine in inflammatory bowel disease (IBD) has increased significantly. Allopathic treatment of IBD leads to several side effects; therefore, the use of the herbal formulation is promising. Aegle Marmelos, Bombax malabericum, and Hollarrhena antidysentrica plants have been used to treat IBD. Objective: This study aimed to evaluate a designed polyherbal formulation in experimentally induced inflammatory bowel disease in rats and validate a mathematical model derived by Box-Behnken experimental design for optimized polyherbal formulation for the treatment of IBD in experimental rats by checkpoint analysis. Methods: Three-level Box-Behnken design was selected to optimize the dose. Polyherbal formulation that consisted of plant extracts of Aegle Marmelos (X1), Bombax malabericum (X2), and Hollarrhena antidysentrica (X3) in different ratios was selected as an independent variable. Polynomial equations were established based on analysis of variance (ANOVA). To validate the chosen polynomial equation, checkpoint analyses were performed. The percentage of predictive error is presented. Results: ANOVA reveals that X2 plant does not have any significant impact on the response surface. The checkpoint batch showed the experimental values of CMDI and Disease activity index (DAI) as 1.33 and 0.66, respectively. It is worthwhile to note that the observed values were quite close to the calculated values of CMDI. A little difference in the value of DAI may be attributed to the inherent variation observed in animal studies. Conclusion: From this study, it was concluded that a dose of 100 mg/kg of Aegle marmelos, a dose of 300 mg/kg of Bombax malabericum, and a dose of 200 mg/kg of Holarrhena antidysentrica will be effective in IBD patients.

Background: Empirical antibiotics among outpatients with Lower Respiratory Tract Infections (LRTIs) are scarcely allocated in Indonesia. The study aims to evaluate the pathogens causing LRTIs, drug sensitivity test and the minimum inhibitory concentrations of 90% (MIC90) of Cefditoren, Azithromycin, Amoxicillin-Clavulanic Acid, and Cefixime. Methods: The study was performed in adult outpatients with LRTI that can be expectorated. Patients with diabetes mellitus, HIV, lung tuberculosis, renal or hepatic failure, and hemoptysis were excluded. We performed bacterial culture, antibiotic sensitivity, and MIC measurement of four antibiotics. Results: There were 126 patients with LRTIs, and 61 patients were eligible for the study. We identified 69 bacteria. We found Klebsiella pneumonia (n=16; 26.23%), Staphylococcus aureus (n=11; 18%), Pseudomonas aeruginosa (n=8; 13.11%), Acinetobacter baumanii complex (n= 4; 6.55%), Streptococcus pneumonia (n=3; 4.9%) and others bacteria as causes of LRTI. Testing MIC90 of Cefditoren and three empiric antibiotics on LRTI found that Cefditoren has a lower MIC of 90 for K. pneumonia (0.97(2.04) μg.mL^-1) and S. pneumonia (0.06(0.00)μg.mL^-1) than other antibiotics, but almost the same as Cefixime ((0.05(0.16)μg.mL-1) and (0.38(0.17)μg.mL-1). MIC90 Cefditoren for S.aureus (3.18(3.54)μg.mL-1) and P.aeruginosa (9.2(3.53)μg.mL-1) is lower than Cefixime but higher than Azithromycin and Amoxicillin-Clavulanic acid. Reference data MIC90 of Cefditoren for LRTI bacteria is lower than the other three oral empirical antibiotics. Conclusion : In vitro studies of an outpatient LRTI in Surabaya found gram-negative bacteria dominant. Cefditoren can inhibit K.pneumonia and S.pneumonia has a lower MIC90 compared to other antibiotics. Cefditoren can inhibit gram-negative and positive bacteria causing LRTI.

Background: Trichophyton spp., as pathogenic species to humans and animals, cause different forms of dermatophytosis through the production of particular enzymes, playing an essential role in tissue invasion. Among these, herein, keratinase was investigated, for the specific case of Trichophyton mentagrophytes, as a target of the effects of Allium hirtifolium and Allium jesdianum extracts, thus pharmacological potential of these plants was studied against keratinase activity. Methodology: Sampling was carried out on 20 bald patients from medical diagnostic laboratories and mycology centers, with suspected dermatophytosis of scalp. For confirming the presence of Trichophyton mentagrophytes in the specimens, different laboratory procedures were applied. Trichophyton mentagrophytes isolates were cultured on a screening medium containing keratin to verify production of the keratinase enzyme. The best enzyme-producing isolate was selected by measuring diameter of transparent halo around colony to be used in subsequent stages. Afterwards, the optimized conditions maximizing enzyme production and activity were determined. Finally, the inhibitory effect of different dilutions of aqueous and alcoholic extracts of Allium jesdianum and Allium hirtifolium on extracellular keratinase activity was studied. Results: Sixteen out of 20 fungal isolates were identified as the Trichophyton mentagrophytes. The most desirable reduction on keratinase activity was reported for dilution values of 50 and 100 mg/ml of both aqueous and ethanolic extracts of A.jesdianum, though much more significant decrease belonged to the latter, and for dilution values of 25 and 100 mg/ ml of both aqueous and ethanolic extracts of A.hirtifolium. Conclusion: Concerning our results, it is suggested that paying special attention to these natural compounds for the treatment of dermatophytosis could be remarkably effective, considering significant production of keratinase observed in T. mentagrophytes, and they are beneficial, as they have no side effects and offer an alternative to currently available medications, which are under the restriction of drug resistance.

Background: Urinary tract infections (UTIs) are the most frequent bacterial infections commonly seen in females. A high degree of antimicrobial resistance in uropathogens has challenged the use of therapeutic agents. Fosfomycin, which is an old antibiotic with distinctive characteristics, seems to be a promising novel therapeutic agent with a good bactericidal activity towards multi-drug resistant (MDR) uropathogens. Objectives: The main objective of the study is to evaluate the antibacterial activity of fosfomycin among uropathogens causing cystitis. Methods: The study was carried out between 2017-2018. A total of 2060 UTI suspects from outpatient departments (OPDs) and inpatient departments (IPDs) were screened. Out of 2060 screened patients, 1658 were IPD patients, and 402 were OPD patients. The patient’s midstream urine samples were collected aseptically and processed according to standard protocols. The frequency of extendedspectrum- beta lactamases (ESBLs) producer and carbapenem resistance were estimated, respectively. Cultures with significant growth of uropathogens were identified, and minimum inhibitory concentration (MIC) to fosfomycin was determined by agar dilution (AD) and by E-test methods. Results: 184 out of 2060 (8.9%) urine samples showed significant growth of uropathogens. Uropathogenic Escherichia coli (UPEC) (64%, 118/184) was found to be the most isolated uropathogen. Among these Gram-negative uropathogens, 80% were ESBLs producers, 43.2% were carbapenemresistant, and 78% isolates were found to be MDR. The fosfomycin susceptibility for UPEC was 95% by the AD method. Conclusions: This study suggests that fosfomycin is reasonably effective and can be used in the treatment of MDR uropathogens along with uncomplicated UTIs.

Background: Candida species are the most important fungal pathogens and are sometimes considered the fourth most common cause of infection in hospitals. Today, research needs to be conducted on the antifungal effect of silver nanoparticles (AgNPs) due to toxicity, side effects, and drug interactions of antifungal chemical drugs. Objective: Therefore, this study was conducted to evaluate the antifungal activity of AgNPs on Candida albicans, Candida dubliniensis, and Candida guilliermondii. Methodology: Antifungal activity of AgNPs on Candida albicans, Candida dubliniensis, and Candida guilliermondii was assessed by agar and macrodilution diffusion methods in an in-vitro investigation. Structural changes were investigated by scanning electron microscope (SEM). Then, the obtained data were evaluated by SPSS statistical software. Results: Based on the results, the mean diameter of growth inhibition halos by AgNPs was equal to 20, 20.2, and 40.7mm for Candida albicans, Candida dubliniensis, and Candida guilliermondii, respectively. The minimum inhibitory concentrations (MIC) equal 62.50, 31.25, and 15.62 mg/ml for Candida albicans, Candida dubliniensis, and Candida guilliermondii, respectively. The minimum fungicidal concentrations (MFC) were equal to 125, 62.50, and 31.25 mg/ml for Candida albicans, Candida dubliniensis, and Candida guilliermondii, respectively. Conclusion: Our results revealed that AgNPs inhibit the growth of Candida albicans, Candida dubliniensis, and Candida guilliermondii. SEM observations also showed that NPs disrupted cell membrane/wall. Changes in yeast levels from smooth to uneven were also observed.

Background: The literature review has highlighted the issues related to the poor mechanical strength of chitosan-based microparticles. In an attempt to resolve the drawbacks, the microparticles were prepared with a suitable combination of poloxamer-188 (pluronic) and chitosan-based hydrogels. Objective: The current study dealt with urapidil-loaded chitosan microparticles incorporating chitosanbased hydrogels and small polyanionic electrolytes. The mechanical strength was ascertained by entrapment efficiency and texture analyzer. Methods: Chitosan-based hydrogels and the combination of poloxamer and further microparticles were prepared by the counter-ion aggregation technique in a polyanionic electrolyte medium (20 % w/v). During the preparation, poloxamer was incorporated to improve the mechanical strength, which was ascertained in terms of adhesive strength (tensile strength) by texture analyzer and entrapment efficiency. The prepared microparticles were also subjected to micrometric studies, swelling index, surface morphology study, drug-polymer interaction study, and zeta analysis. Results: A remarkable increase in entrapment efficiency (maximum of 78.56 % from SSP4) was observed with the progressive increase in poloxamer-188. In addition to that, the adhesive strength was also studied by a texture analyzer for all microparticles. Sodium citrate-based products exhibited superior adhesive strength values than sodium sulfate- and sodium tripolyphosphate-based products, indicating the significance of incorporating poloxamer-188. A significant finding was also recorded for the swelling properties at microenvironmental pH attributed to polyanions. It was observed that sodium TPP microparticles continued to swell in a phosphate buffer of pH 6.8. Zeta value was found to be maximum with -5.2 mV; however, it could further be improved by adding electrolytes. TPP4 showed a comparatively larger particle size of 8.07 μm. Polydispersity index value revealed homogenous dispersion of microparticles. SEM study revealed prominent porous surfaces for sodium tripolyphosphate microparticles. Conclusion: The study revealed that the addition of poloxamer-188 improved the mechanical strength, identified by entrapment efficiency and texture analysis. SCP4 microparticle was found to be the best formulation among all.