Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences最新文献

Purpose: Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning.

Methods: In this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens.

Results: Of 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients.

Conclusion: Combination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.

Objectives: The main objective of the present review is to explore and examine the effectiveness of currently developed novel techniques to resolve the issues which are associated with the herbal constituents/extract.

Methods: A systematic thorough search and collection of reviewed information from Science direct, PubMed and Google Scholar databases based on various sets of key phrases have been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information.

Result: Herbal drugs are gaining more popularity in the modern world due to their applications in curing various ailments with minimum toxic effects, side effect or adverse effect. However, various challenges exist with herbal extracts/plant actives such as poor solubility (water/lipid), poor permeation, lack of targeting specificity, instability in highly acidic pH, and liver metabolism, etc. Nowadays with the expansion in the technology, novel drug delivery system provides avenues and newer opportunity towards the delivery of herbal drugs with improved physical chemical properties, pharmacokinetic and pharmacodynamic. Developing nano-strategies like Polymeric nanoparticles, Liposomes, Niosomes, Microspheres, Phytosomes, Nanoemulsion and Self Nano Emulsifying Drug Delivery System, etc. imparts benefits for delivery of phyto formulation and herbal bioactives. Nano formulation of phytoconstituents/ herbal extract could lead to enhancement of aqueous solubility, dissolution, bioavailability, stability, reduce toxicity, permeation, sustained delivery, protection from enzymatic degradation, etc. CONCLUSION: Based on the above findings, the conclusion can be drawn that the nano sized novel drug delivery systems of herbal and herbal bioactives have a potential future for upgrading the pharmacological action and defeating or overcoming the issues related with these constituents. The aims of the present review was to summarize and critically analyze the recent development of nano sized strategies for promising phytochemicals delivery systems along with their therapeutic applications supported by experimental evidence and discussing the opportunities for further aspects.

Purpose: Mohs' paste, which is composed of zinc chloride and zinc oxide starch, is used for hemostasis of superficial malignancy in the clinical setting. We investigated the concentration of intramuscular zinc in mice after Mohs' paste application and evaluated its relationship with angiogenesis from the perspective of blood flow levels within 24 h.

Methods: Male C57BL/6JJmsSlc mice were administered single dose of Mohs' paste at 25%, 50%, and 75% after unilateral hind limb surgery, and glycerin, a viscosity modifier, was administered to the control group (0%). Hind limb blood flow levels were measured with a laser Doppler perfusion imaging system (n = 6). The amounts of intramuscular zinc and vascular endothelial growth factor-A (VEGF-A) expression were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and western blotting, respectively (n = 5 or 3).

Results: Blood flow levels were significantly decreased in the 50% group after 8 h, and significantly decreased in the 25% and 50% groups after 24 h. Intramuscular zinc was significantly increased in the 50% and 75% groups after 8 h. Western blotting showed that VEGF-A levels were significantly increased in the 25% and 50% groups after 8 h. Based on analytical experiments and biological investigation, we predicated the pharmacological effect of Mohs' paste and found over 50% of it is critical in the blood flow and angiogenesis suppression after more than 8 h of its application.

Conclusions: The results suggest that the mechanism of blood flow suppression is independent of VEGF-A levels and might suppress future angiogenesis. Our findings support that of previous studies, in which Mohs' paste was expected to induce hemostasis and suppress angiogenesis. It is an excellent ointment that facilitates hemostasis by suppressing blood flow regardless of angiogenesis, and may be apt for situations where hemostasis is required in the clinical setting.

Background and objective: Spinal cord injury (SCI) is a major disabling disorder for which no effective treatment has yet been found. Regenerative incapability of neuronal cells as well as the secondary mechanisms of injury are the major reasons behind this clinical frustration. Thus, here we fabricated an erythropoietin-chitosan/alginate (EPO-CH/AL) hydrogel and investigated its local therapeutic effects on the apoptotic and inflammatory indices of SCI secondary injury.

Methods: EPO-CH/AL hydrogels were fabricated by the ionic gelation method, and they were characterized using SEM and FTIR. In vitro drug release profile of EPO-CH/AL hydrogels was evaluated by UV-vis spectroscopy. Experimental SCI was inflicted in rats which were then treated with CH/AL hydrogels containing different doses of EPO (1000, 5000 and 10,000 IU/kg). The relative expression of Bax and Bcl2 (apoptosis index) and active and inactive forms of NF-κB (inflammation index) were assessed using western blot. Total serum levels of TNF-α were also assessed with ELISA, and histopathological and immunohistochemistry studies were carried out to check the overall changes in the injured tissues.

Results: In vitro drug release test indicated that the EPO-CH/AL hydrogels had a sustained- and controlled-release profile for EPO under these conditions. All the fabricated hydrogels dramatically reduced the elevated inflammation and apoptosis indices of the SCI-inflicted rats (p ≤ 0.05). Nevertheless, only EPO-CH/AL hydrogel (1000 IU/kg EPO) significantly improved the tissue repair and histopathological appearance of the spinal cord at the sites of injury.

Conclusion: Based on our findings, EPO-CH/AL hydrogel (1000 IU/kg EPO) can effectively improve experimental SCI in rats via inhibiting apoptosis and inflammation. Further studies are warranted to elucidate the contributing role of the scaffold in the observed effects.

Introduction: Sodium-glucose cotransporter (SGLT2) inhibitors may additionally benefit patients with diabetes by improving their erythropoiesis followed by the elevation of hemoglobin and hematocrit levels.

Reason for the report: In the case described, severe normocytic normochromic anemia was resolved when empagliflozin had been introduced to the therapy. A 78-year-old male patient was admitted to our hospital with a non-ST-segment elevation myocardial infarction. His past medical history included diabetes, right coronary artery angioplasty, myocardial infarction and paroxysmal atrial fibrillation which required anticoagulant treatment. When examined, severe normocytic normochromic anemia was also diagnosed. About two years prior to his admission, the patient began suffering from persistent anemia despite the modification of his anticoagulant therapy with warfarin, rivaroxaban and dabigatran. An extensive evaluation failed to provide an explanation for his anemia.

Outcome: Eventually, only the introduction of empagliflozin successfully increased the values of hemoglobin and hematocrit. Therefore, it transpires that SGLT2 enhances erythropoietin (EPO) secretion which subsequently raises hematocrit levels in patients with severe anemia.

Background: English ivy (Hedera helix) is commonly used to reduce productive cough symptoms by acting as expectorant therapy. The safety of Hedera helix extract during pregnancy was not established yet. This study aims to determine the safety of English ivy leaf extract on newborns.

Objectives: To determine the weight, APGAR (Activity-Pulse-Grimace-Appearance-Respiration) score, and health status of the newborns among the studied groups.

Methods: A retrospective multicenter cohort study was conducted during the fourth quarter of 2020 on 245 pregnant women and their newborns in two hospitals located in Riyadh, Saudi Arabia. The women were divided into an exposed group (N = 165) who used English ivy leaf extract syrup during pregnancy, and a control group (N = 80) who were not using any natural-pharmaceutical product for cough.

Results: The mean weight of the newborns in the exposed group was 3 kg compared to 2.8 kg in the control group (p-value < 0.05). The median APGAR score of the newborns in the exposed group was 8.5/10 compared to 8.0/10 in the control group (p-value > 0.05). There were no significant differences regarding the percentages of full-term and preterm newborns in the exposed and control groups (78.8% vs. 76.3%, and 21.0% vs. 24.0%, respectively, odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.45-1.63, p-value > 0.05). Regarding the newborns' health complications reported, there was no statistical difference in the percentages of full-term newborns diagnosed with at least one health complication between the exposed and control groups (0.6 vs. 3.8, OR = 0.15, 95% CI = 0.01-1.47, p-value > 0.05).

Conclusion: Hedera helix (English ivy) leaf extract syrup was safe to be used in short term during pregnancy for the fetus.

Chemotherapy is the most common treatment strategy for cancer patients. Nevertheless, limited drug delivery to cancer cells, intolerable toxicity, and multiple drug resistance are constant challenges of chemotherapy. Novel targeted drug delivery strategies by using nanoparticles have attracted much attention due to reducing side effects and increasing drug efficacy. Therefore, the most important outcome of this study is to answer the question of whether active targeted HA-based drug nanocarriers have a significant effect on improving drug delivery to cancer cells.This study aimed to systematically review studies on the use of hyaluronic acid (HA)-based nanocarriers for chemotherapy drugs. The two databases MagIran and SID from Persian databases as well as international databases PubMed, WoS, Scopus, Science Direct, Embase, as well as Google Scholar were searched for human studies and cell lines and/or xenograft mice published without time limit until 2020. Keywords used to search included Nanoparticle, chemotherapy, HA, Hyaluronic acid, traditional medicine, natural medicine, chemotherapeutic drugs, natural compound, cancer treatment, and cancer. The quality of the studies was assessed by the STROBE checklist. Finally, studies consistent with inclusion criteria and with medium- to high-quality were included in the systematic review.According to the findings of studies, active targeted HA-based drug nanocarriers showed a significant effect on improving drug delivery to cancer cells. Also, the use of lipid nanoparticles with a suitable coating of HA have been introduced as biocompatible drug carriers with high potential for targeted drug delivery to the target tissue without affecting other tissues and reducing side effects. Enhanced drug delivery, increased therapeutic efficacy, increased cytotoxicity and significant inhibition of tumor growth, as well as high potential for targeted chemotherapy are also reported to be benefits of using HA-based nanocarriers for tumors with increased expression of CD44 receptor.

Background: MicroRNA (miR)-34a, as a master tumor suppressor in colorectal cancer (CRC), could regulate multiple genes participating in tumor proliferation, invasion, immune evasion, and inflammation-induced progression. Exosomes, as novel nano-carriers, were found to be capable of shuttling crucial mediators to various cells. Since the conventional CRC therapeutics currently are a matter of debate, implication of microRNAs in malignancy remedies have been addressed illustrating promising outlooks.

Objectives: In this study, we aimed to investigate the delivery of miR-34a to CRC cell line CT-26 by encapsulating into tumor-derived exosomes (TEXs), in order to evaluate the anti-proliferative and progressive effects of the novel nano-carrier complex under in vitro condition.

Methods: Exosomes were purified from the starved CT-26 cells and then enriched by miR-34a using the calcium chloride (Cacl₂) modified solution. Following the detection of miR-34a expression in the enriched TEXs, the viability of CT-26 cells treated by multiplicity concentrations of either TEXs or TEX-miR-34a was examined. Moreover, the apoptosis rate of the cells was evaluated, and the migration of CT-26 cells subjected to both TEX-miR-34a and TEX was also measured. Thereafter, the expressions of miR-34a target genes, as IL-6R, STAT3, PD-L1, and VEGF-A, which play roles in tumor progression, were determined in the treated CT-26 cells.

Results: The viability of CT-26 cells was harnessed following the treatment with TEX-miR-34a and the apoptosis levels of the cells were also observed to be enhanced dose-dependently. TEX-miR-34a was able to diminish the migration rate of the TEX-miR-34a treated cells and the expressions of IL-6R, STAT3, PD-L1, and VEGF-A were significantly restricted. Moreover, TEXs alone increased the apoptosis rate of tumor cells and repressed the proliferation and migration of these cells which were boosted by enrichment of TEXs with miR-34a.

Conclusion: Exosomes isolated from the starved CT-26 cells were found to have a potential to deliver miR-34a into tumor cells properly with high functionality maintenance for miR-34a in case of regulating genes related to tumor progression and TEXs which showed no positive effect favoring cancer cells, presumably act as a favorable adjuvant in the CRC therapy.

Introduction: Protein kinase C (PKC) is a promising drug target for various therapeutic areas. Natural products derived from plants, animals, microorganisms, and marine organisms have been used by humans as medicine from prehistoric times. Recently, several compounds derived from plants have been found to modulate PKC activities through competitive binding with ATP binding site, and other allosteric regions of PKC. As a result fresh race has been started in academia and pharmaceutical companies to develop an effective naturally derived small-molecule inhibitor to target PKC activities. Herein, in this review, we have discussed several natural products and their derivatives, which are reported to have an impact on PKC signaling cascade.

Methods: All information presented in this review article regarding the regulation of PKC by natural products has been acquired by a systematic search of various electronic databases, including ScienceDirect, Scopus, Google Scholar, Web of science, ResearchGate, and PubMed. The keywords PKC, natural products, curcumin, rottlerin, quercetin, ellagic acid, epigallocatechin-3 gallate, ingenol 3 angelate, resveratrol, protocatechuic acid, tannic acid, PKC modulators from marine organism, bryostatin, staurosporine, midostaurin, sangivamycin, and other relevant key words were explored.

Results: The natural products and their derivatives including curcumin, rottlerin, quercetin, ellagic acid, epigallocatechin-3 gallate, ingenol 3 angelate, resveratrol, bryostatin, staurosporine, and midostaurin play a major role in the management of PKC activity during various disease progression.

Conclusion: Based on the comprehensive literature survey, it could be concluded that various natural products can regulate PKC activity during disease progression. However, extensive research is needed to circumvent the challenge of isoform specific regulation of PKC by natural products.

Background: Several species of Verbenaceae have been widely used in medicine, and some species of Verbenaceae have been observed good insecticidal activity, such as Lantana camara and Vitex negundo. There is no report about repellent activity of Clerodendrum bungei Steud. (C. bungei) against stored product insects. The chemical composition of C. bungei essential oil (EO) were identified, repellent activity of methanol extract, EO of C. bungei and two main components of EO against T. castaneum, L. serricorne and L. bostrychophila were evaluated for the first time.

Results: EO of C. bungei was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS) and GC. A total of 25 components of the C. bungei EO were identified. The principal compounds in the EO were myristicin (75.0%), 2,2,7,7-Tetramethyltricyclo[6.2.1.0(1,6)]undec-4-en-3-one (4.1%) and linalool (3.4%). Results of bioassays indicated that C. bungei EO exerted strong repellent activity against three target insects. As main constituents, myristicin and linalool also had certain repellency.

Conclusion: This work suggests that the EO of C. bungei has promising potential to develop into botanical repellents for the control of pest damage in warehouses and grain stores.