Iranian Journal of Pharmaceutical Research最新文献

Background: Calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors are essential for maintaining transplanted organs. However, determining the appropriate dosage and predicting blood concentrations of these drugs based solely on net body weight may be inadequate. Previous studies have presented contradictory results regarding the impact of obesity on drug concentrations and transplant success.

Objectives: This study aims to evaluate various weight indices to identify the most reliable indicator of weight that correlates with the blood levels of drugs used in organ transplantation.

Methods: This retrospective descriptive study included patients from nephrology clinics affiliated with Isfahan University of Medical Sciences who were taking calcineurin and/or mTOR inhibitor drugs. Data extracted from medical records included demographic and clinical information, such as height, weight, and various weight indices (total/ideal/adjusted body weight, lean body mass (LBM), Body Mass Index, and predicted normal weight), as well as blood levels of immunosuppressive drugs at each patient's visit. The dosages of each drug (mg/kg) were analyzed to determine which weight indices best correlated with the obtained blood concentrations, using the Generalized Estimating Equation (GEE) model with logistic regression, an independent correlation matrix, and a binary distribution for data analysis.

Results: The study analyzed the medical records of 71 patients. Trough (C0) concentrations of drugs were evaluated in relation to each weight index, and odds ratios (OR) were calculated for statistical comparison. All weight indices increased the likelihood of achieving appropriate concentrations for cyclosporine, tacrolimus, and sirolimus. Drug dosing based on LBM (OR: 1.028), ideal body weight (OR: 1.075), and total body weight (OR: 1.041) showed the strongest correlations with achieving proper blood levels for cyclosporine, tacrolimus, and sirolimus, respectively.

Conclusions: Integrating various weight indices for calculating individualized doses (mg/kg) of each immunosuppressive drug increases the likelihood of achieving appropriate blood concentrations. However, the optimal weight index varies for each drug. Further studies, particularly those incorporating therapeutic drug monitoring (TDM) plans in transplant centers, are warranted to validate and generalize these findings, providing a potential avenue for improving immunosuppressive therapy and enhancing transplant outcomes.

Background: Migraine is a prevalent, chronic neurovascular disorder that incurs significant indirect costs due to productivity loss. Preventive therapy is an effective way to alleviate the societal and healthcare burden of migraine. Approximately 14% of both the global and Iranian populations are affected by migraine, which has substantial economic implications.

Objectives: To determine the cost-effectiveness of Erenumab compared to Topiramate for migraine treatment in Iran.

Methods: A three-state Markov model was used to evaluate the cost-effectiveness of Erenumab. The model considered both direct and indirect costs from a societal perspective. The incremental cost-effectiveness ratio (ICER) was calculated by determining the cost per quality-adjusted life year (QALY) gained. Costs and QALYs were discounted annually at 5.8% and 5%, respectively. Deterministic and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of the model.

Results: The average cost for patients using the Erenumab strategy was 16,836 USD over five years, whereas the average cost for the Topiramate strategy was estimated to be 2,660 USD. Additionally, the average QALYs for the Erenumab and Topiramate strategies were 3.64 and 3.46, respectively. The ICER for the Erenumab strategy was 78,923 USD/QALY. This ICER is significantly higher than the fixed Iranian willingness-to-pay (WTP) threshold of 2,456 USD.

Conclusions: The study concludes that preventive treatment of migraine with Erenumab, compared to Topiramate, is not cost-effective in Iran based on current prices. Therefore, for Erenumab to be considered cost-effective, a significant price reduction is necessary for its entry into the Iranian pharmaceutical market.

Background: Breast cancer is the most common cancer among women worldwide, impacting not only the patients but also their families and communities. Tournefortia mutabilis vent. is a plant endemic to Mexico, traditionally used in Zapotec medicine for the treatment of cancer.

Objectives: This study aims to evaluate the effects of the chloroformic extract of T. mutabilis vent. leaves on cell proliferation and cell death in MCF-7 cells.

Methods: The effect of the extract on MCF-7 cell proliferation was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet staining. Apoptosis was evaluated through fluorescein diacetate/propidium iodide staining and caspase-3, -6, and -9 activity assays.

Results: The half-maximal inhibitory concentration (IC50) of the T. mutabilis vent. extract on MCF-7 cell proliferation at 48 hours and 72 hours after treatment was 86.4 µg/mL and 2.74 µg/mL, respectively. We observed that the extract and its semi-purified fractions induced cell death through the activation of caspases 3, -6, and -9.

Conclusions: Tournefortia mutabilis vent. is a potential source of compounds with antiproliferative and pro-apoptotic activities on the MCF-7 cell line, primarily through the intrinsic pathways of apoptosis.

Background: Chronic kidney disease (CKD), which progresses to end-stage renal disease (ESRD) and requires maintenance hemodialysis (MHD), is a global health issue. Inflammation in MHD patients is associated with increased mortality and cardiovascular events. Zinc, essential for immune function and possessing anti-inflammatory properties, is frequently deficient in these patients and could potentially help mitigate inflammation.

Objectives: This study aims to assess the impact of zinc supplementation on inflammatory biomarkers, specifically (CRP) and the neutrophil-to-lymphocyte ratio (NLR), in MHD patients.

Methods: In a double-blind, randomized controlled crossover trial conducted at Labafinejad Hospital, Tehran, MHD patients with zinc deficiency were initially allocated to either a zinc supplementation group or a placebo group. After 30 days, the groups were crossed over, with patients initially receiving zinc now receiving a placebo and vice versa. The primary outcome was changes in serum zinc levels, while secondary outcomes focused on CRP and NLR levels.

Results: Significant changes in serum zinc levels were observed in both groups from baseline to Month 2 (drug-placebo group: Mean change -15.9±10.33 µg/dL, P < 0.05; placebo-drug group: Mean change -14.70 ± 12.58 µg/dL, P < 0.05). A significant initial reduction in CRP levels at Month 1 (P = 0.045) was not sustained at Month 2 (P = 0.812). No statistically significant changes in NLR were noted. Improvements in quality of life, including reductions in muscle pain and skin dryness, were significant in the drug-placebo group (P < 0.05).

Conclusions: Zinc supplementation in MHD patients significantly improved serum zinc levels and initially reduced CRP levels, highlighting its potential role in managing inflammation. Although the impact on NLR was not significant, overall patient outcomes and quality of life showed promising improvements.

Background: Dry eye disease (DED) is a multifactorial condition characterized by ocular surface inflammation, tear film instability, and corneal epithelial damage. Current treatments often provide temporary relief without addressing the underlying inflammatory mechanisms.

Objectives: This study examined the therapeutic potential of crocin and nobiletin, two naturally derived compounds with well-known antioxidant and anti-inflammatory properties, in a mouse model of DED induced by lacrimal gland excision (LGE).

Methods: Thirty female Balb/c mice were divided into five groups (n = 6 each): Control (sham surgery), untreated DED, nobiletin-treated DED (32.75 µM), crocin-treated DED (34 µM), and 1% betamethasone-treated DED. Treatments were administered three times daily for 28 days. Ocular tissues were evaluated using Hematoxylin and Eosin (H&E) staining and fluorescein staining. Conjunctival inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α), were measured by enzyme-linked immunosorbent assay (ELISA).

Results: Histological analysis showed that the crocin and nobiletin treatment groups exhibited reduced epithelial disruption, keratinization, and inflammatory cell infiltration compared to the untreated DED group. The ELISA assay revealed that both compounds efficiently inhibited the production of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β, which are key mediators of DED pathogenesis. Fluorescein staining further confirmed the protective impact of crocin and nobiletin on corneal epithelial integrity. Moreover, the anti-inflammatory and epithelial-preserving effects of these compounds were comparable to those of the corticosteroid betamethasone.

Conclusions: Overall, these findings suggest that crocin and nobiletin have therapeutic potential for DED management by modulating inflammatory responses and enhancing ocular surface healing. These naturally derived compounds offer promising avenues for the development of safer and more effective treatments for this challenging condition. However, further investigations, including clinical trials, are essential to elucidate the underlying mechanisms of action and optimize therapeutic approaches.

Background: Hormonal imbalances related to women's health, physical activity, and fluctuations are prevalent metabolic disorders in several nations and have significantly impacted women's health for an extended period. The application of individual or combined botanical extracts in traditional, alternative, and complementary medicine is employed to manage and alleviate these issues.

Objectives: The objective of this study is to examine the suppressive properties of horehound (Marrubium vulgare L.) on pivotal hormones associated with feminine disorders.

Methods: The horehound plant was exposed to ultrasonic radiation while five different solvents (methanol, ethyl acetate, n-hexane, acetone, and water) were used to extract its components. The individuals were isolated using high-performance thin-layer chromatography (HPTLC). The most powerful compounds were analyzed using a direct antioxidant assay (DPPH test) and a hormone inhibitory assay (Oestrogen, Progesterone, Estradiol, and Testosterone) on the HPTLC plate. The compounds that had a significant effect were then identified using LC-ESI/MSMS.

Results: The antioxidant properties of the extracts and hormone inhibitors were evaluated, and the substances were separated from the HPTLC plate and analyzed using mass spectrometry. The results showed strong antioxidant capabilities, with an IC50 range of 8.24 - 12.42 µg/mL. Moreover, the plant extract showed beneficial effects on hormones associated with female health issues.

Conclusions: The extract was subjected to chemical and molecular analysis using the HPTLC technique, followed by LC-ESI/MSMS. The study revealed the presence of vulgarole, marrubiin, and marrubenol chemicals.

Background: Despite the availability of tetanus-diphtheria (TD) vaccines in Iran, the seroconversion rate of these products as a booster dose is unknown.

Objectives: This study evaluates the seroconversion rate of the Iranian Td vaccine in adults who have not been vaccinated in the past decade.

Methods: In this study, 20 adult volunteers aged 18 to 60 who had not received the Td vaccine in the past decade received a booster dose of the Iranian Td vaccine. Twenty-eight days after vaccination, the seroconversion rate was evaluated using the ELISA method. Vaccine adverse events were monitored at three time points after vaccination.

Results: Seroconversion rates with the Iranian Td vaccine boosters were 75% and 90%, respectively, based on a 4-fold increase in anti-tetanus toxoid antibody titers and a 2- and 4-fold combination. Significant associations were found between the demographic data, specifically female gender and age 43 years and older, with seroconversion rates. Injection-site pain was the most common adverse reaction, with a frequency of 35%. No adverse events were reported between one week and one month after vaccination.

Conclusions: Results showed that a booster dose of the Iranian Td vaccine produced a protective titer (> 0.1 IU/mL) and a long-term protective titer (> 1.0 IU/mL) in 100% of participants. The seroconversion rate of the Iranian Td vaccine was comparable to other common tetanus vaccines, including Tenivac^®, Adacel^®, Infanrix^®, Tetavax^®, and Vacteta^®. The proportion of suitable candidates for plasma donation, based on minimum (2 IU/mL) and maximum (10 IU/mL) anti-tetanus toxoid antibody titers, was 100% and 45%, respectively.

Background: High mobility group box 1 (HMGB1) plays an essential role in various pathological conditions, including inflammation, fibrosis, autoimmune diseases, and carcinogenesis. The quantification of HMGB1 in body fluids holds promise for clinical applications.

Objectives: This study aimed to isolate high-affinity single-stranded DNA (ssDNA) aptamers that target HMGB1.

Methods: In this study, ssDNA aptamers were selected using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The affinity and specificity of the aptamers were evaluated through South-Western blot analysis, enzyme-linked aptamer sorbent assay (ELASA), and aptamer-based histochemistry staining. The impact of the aptamers on the biological activity of HMGB1 was tested in the human acute monocytic leukemia cell line, THP-1.

Results: An aptamer (H-ap25, dissociation constant = 8.20 ± 0.53 nmol/L) with high affinity for the HMGB1 B box was generated. Further experiments verified that H-ap25 can be used to detect HMGB1 in South-Western blot analysis, ELASA, and aptamer-based histochemistry staining. Moreover, H-ap25 significantly augmented HMGB1-induced expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, Toll-like receptor 9 (TLR9), and activation of NF-κB in THP-1 cells.

Conclusions: Our results demonstrated that H-ap25 can be used both as an enhancer of HMGB1 and as a probe in research.

[This corrects the article DOI: 10.22037/ijpr.2019.2322.].

Background: Alprazolam, a commonly prescribed benzodiazepine, poses risks of toxicity and severe withdrawal symptoms. There is an urgent need for a rapid and sensitive diagnostic method for detecting alprazolam poisoning.

Objectives: This study aimed to detect alprazolam poisoning through Fourier-transform infrared (FTIR) analysis of saliva, addressing the need for a quick, cost-effective, and sensitive diagnostic method for poison control and differential diagnosis.

Methods: Saliva samples were collected from 45 individuals with benzodiazepine toxicity, therapeutic consumption, and normal health status, as well as from a control group. The samples were analyzed using FTIR spectroscopy. The resulting spectra were processed with OriginPro software, and statistical analyses were performed using receiver operating characteristic (ROC) and analysis of variance (ANOVA).

Results: The average age of the studied population was approximately 45 years, with women being the most affected by poisoning. Fourier-transform infrared analysis revealed significant differences in the structure of lipids between poisoned individuals, therapeutic receivers, and healthy individuals (P < 0.0001).

Conclusions: Fourier-transform infrared analysis of saliva is a fast and accurate method for diagnosing alprazolam poisoning within minutes, enabling prompt and appropriate treatment during critical life-threatening situations. This non-invasive technique has the potential to guide treatment staff toward effective treatment options.