A validated micellar LC method for simultaneous determination of furosemide, metoprolol and verapamil in human plasma

An accurate and precise micellar LC method coupled with UV and fluorimetric detectors was developed and validated for the simultaneous analysis of furosemide, metoprolol and verapamil in human plasma. The total analysis time was 25 min (12 min for sample preparation and 13 min for drug separation). All drugs possessed linear behavior (r > 0.999 for calibration curves) in their therapeutic concentrations. The mean drug recoveries were 101.9, 100.1 and 100.2% for furosemide, metoprolol and verapamil, respectively. The accuracies (relative error %) were less than 15% for all drugs. Intra- and inter-day precisions (RSD%) were less than 15% and the stability data were acceptable according to the US FDA guideline for bioanalytical method validation.     

The association between urodynamic findings and microvascular complications in patients with long-term type 2 diabetes but without voiding symptoms

Diabetic cystopathy is a common complication of diabetes mellitus, which is assessable by urodynamic study. The purpose of this study was to determine the association between urodynamic findings and microvascular complications (neuropathy, retinopathy, nephropathy) in patients with long-term type 2 diabetes but without voiding symptoms. A total of 66 consecutive patients (26 males and 40 females, age 57.00+/-9.50 years, diabetes duration 14.44+/-6.78 years) with documented type 2 diabetes, low scores at the International Prostate Symptom Score (IPSS) and no subjective complaint of voiding problems were included in the study. Seven urodynamic parameters were considered: detrusor activity, bladder capacity, bladder compliance, first sensation of filling, flow rate, bladder outlet status and post-voiding residue. The following independent associations were found: between female sex and increased bladder capacity (p=0.004), between male sex and both decreased bladder compliance (p=0.023) and bladder outlet obstruction (p=0.001), between old age and both low flow rate (p=0.022) and outlet obstruction (p=0.047), between detrusor instability and shorter duration of diabetes (p=0.044) and between peripheral somatic neuropathy and low flow rate (OR=5.208; 95%CI=1.277-21.277). The Spearman's correlation coefficient for the latter association was 0.356 (p=0.005) and remained significant even after controlling for age, sex, HbA1c and diabetes duration (rho=0.310; p=0.019). In conclusion, searching for microvascular complications might be used to screen for some components of diabetic cystopathy in its asymptomatic phase.     

Effect of COVID-19 on the Number of CT-scans and MRI Services of Public Hospitals in Iran: An Interrupted Time Series Analysis

BackgroundIn February 2020, the Ministry of Health and Medical Education in Iran announced the first case of COVID-19. The aim of this study was to investigate the impact of COVID-19 on the number of CT-Scans and MRI services in public hospitals in western Iran.MethodsWe collected CT-scans and MRI services data from 18 public hospitals via Vice-Chancellor Office, Lorestan University of Medical Sciences from January 2017 to February 2021. Interrupted time series analysis (ITSA) was conducted to assess the impact of COVID-19 on CT-Scans and MRI services. More specifically, ITSA was conducted using ordinary least squares regression with the number of CT-Scans and MRI services per 1,000 registered persons per month as dependent variable.ResultsAt the beginning of the observation period, the monthly rate of CT-Scans was constant (p for trend = 0.267) at 291.9 (from 95%CI 240.5 to 343.4) per 1,000 registered patients. The first case of COVID-19 coincided with an abrupt increase by 211.8 (from 95%CI 102.9 to 320.7) per 1,000 patients. Thereafter, the trend of CT-Scans did not change (p=0.576) compared to the pre-pandemic period. The rate of MRI services was 363.5 per 1,000 per registered patients per month (P = <0.0001) with a slightly decreasing trend (coefficient=-5; 95%CI, -6.9 to -3.1).ConclusionThe findings of this study showed that crises such as COVID-19 can affect the service delivery process. Health policymakers and decision makers should work to prevent potential reductions in health care during events such as COVID-19.     

In vivo gamma-rays induced initial DNA damage and the effect of famotidine in mouse leukocytes as assayed by the alkaline comet assay

Ionizing radiation induces a variety of lesions in DNA, each of which can be used as a bio-indicator for biological dosimetry or the study of the radioprotective effects of substances. To assess gamma ray-induced DNA damage in vivo in mouse leukocytes at various doses and the effect of famotidine, blood was collected from Balb/c male mice after irradiation with 4 Gy gamma-rays at different time intervals post-irradiation. To assess the response, mice were irradiated with doses of gamma-rays at 1 to 4 Grays. Famotidine was injected intra-peritoneally (i.p) at a dose of 5 mg/kg at various time intervals before irradiation. Four slides were prepared from each sample and alkaline comet assay was performed using standard protocols. Results obtained show that radiation significantly increases DNA damage in leukocytes in a dose dependent manner (p < 0.01) when using appropriate sampling time after irradiation, because increasing sampling time after irradiation resulted in a time dependent disappearance of DNA damage. Treatment with only 5 mg/kg famotidine before 4 Gy irradiation led to almost 50% reduction in DNA damage when compared with those animals which received radiation alone. The radioprotective capability of famotidine might be attributed to radical scavenging properties and an anti-oxidation mechanism.     

Topical Silymarin Administration for Prevention of Capecitabine‐Induced Hand–Foot Syndrome: A Randomized,Double‐Blinded,Placebo‐Controlled Clinical Trial

Hand–foot syndrome (HFS) is a frequent dose‐limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine‐induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double‐blinded, placebo‐controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9 weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3 weeks during these 9 weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9^th week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during chemotherapy, but there was a delay for HFS development and progression in silymarin group. Prophylactic administration of silymarin topical formulation could significantly reduce the severity of capecitabine‐induced HFS and delays its occurrence in patients with gastrointestinal cancer after 9 weeks of application. Copyright © 2017 John Wiley & Sons, Ltd.     

Investigation of CD24 and its expression in Iranian relapsing-remitting multiple sclerosis

CD24 is a glycosylphosphatidylinositol (GPI)-linked cell surface glycoprotein expressed in central nervous system cells. Recent investigations have suggested that CD24 participates in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, a limited number of studies have been published regarding the contribution of CD24 to the risk and severity of MS in humans. We investigated the contribution of a CD24 single nucleotide polymorphism (SNP) to MS disease risk and severity. We also studied mRNA expression of the CD24 gene in Iranian MS patients using quantitative real-time polymerase chain reaction (PCR). Our findings showed that the CD24(v/v) genotype was significantly more frequent in MS patients compared with controls (p(c) = .004). Moreover, a statistically significant difference in the Multiple Sclerosis Severity Score (MSSS) was found between MS patients carrying CD24(a/a) and CD24(v/v) genotypes (p = .008). The results also indicated that the expression of CD24 mRNA was 1.7 times more in MS patients compared with controls. In conclusion, our results suggest that the CD24(v/v) genotype influences both MS disease risk and severity in Iranian MS patients, and the high disease severity in CD24(v/v) patients may indicate that they require more aggressive treatment than do patients carrying CD24(a/a).     

Efficacy of an electric toothbrush on plaque control compared to two manual toothbrushes

Objectives: This study aimed to compare an electric toothbrush with two manual toothbrushes, in their relative efficacy to control plaque. Design: Randomised clinical trial. Setting: Kerman Dental School, Iran. Participants: Forty‐five volunteer dental students were randomly assigned to one of three groups. All subjects received a baseline plaque assessment using O’Leary plaque index, and then a prophylaxis to achieve the plaque index of zero. Subjects were trained to brush twice daily, with their assigned device and return after 1 week and then after 2 weeks for plaque assessment. Chi‐squared and ANOVA were mainly used. Main outcome measure: Plaque assessment using O’Leary plaque index. Results: Although Jordan toothbrush consistently resulted in lower plaque indices compared to both manual toothbrushes, those differences were not statistically significant, F(2, 42) = 2.45, P = 0.10. Plaque reduction from week 1 to week 2 was significant in Jordan Power group (60%, from 13.46 to 5.44, P = 0.010) and Panbehriz Classic group (53%, from 20.92 to 9.91, P = 0.007). Conclusion: The results of this study shows no evidence of statistically significant difference in respect to plaque control, between Jordan Power electric toothbrush and either of Oral‐B Advantage or Panbehriz Classic manual brushes in a group of dental students after 2 weeks.     

Controlled release of betamethasone from vitamin E-loaded silicone-based soft contact lenses

Context: Betamethasone (BMZ) is an effective drug which is commonly used as an eye drop for the management of ophthalmic inflammations. Due to low ocular bioavailability, it is necessary to prepare and optimize an ocular drug delivery system for BMZ.

Objective: In this study we tried to use vitamin E diffusion barrier for sustaining BMZ release.

Materials and methods: Three commercial contact lenses were soaked in vitamin E solutions and swelling percentage, diameter, transmittance, binding capacity and release amount and time were evaluated in comparison with non-vitamin E-loaded pure lenses.

Results: The results showed that vitamin E significantly decreased water content of contact lenses whereas, increased the lens diameter in both dry and wet states. It effectively blocked UV radiation which is harmful for the eye surface while had no significant effect on visible transmittance. BMZ loading capacity enhanced and release rate remarkably decreased after using vitamin E as a hydrophobic diffusion barrier.

Discussion and conclusions: This study revealed that vitamin E can be applied as a hydrophobic diffusion barrier for controlling and sustaining BMZ release from silicone-based soft contact lenses into the lachrymal fluid. It can also protect eye tissues as an antioxidant by blocking the UV radiation.     

Comments on “Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors”

European Archives of Psychiatry and Clinical Neuroscience -     

Antitumor activity of novel pyrrolo[2,3-d]pyrimidin-4-ones

Pyrrolo[2,3-d]pyrimidine is known to have a broad spectrum of biological activities, including antitumor activity. The cytotoxic properties of six novel pyrrolo[2,3-d]pyrimidin-4-ones in vitro were investigated on four different human cancer cell lines. Meanwhile, the role of apoptosis was explored. Malignant cells were cultured in RPMI medium and incubated with different concentrations. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using DAPI (4'-6-diamidino-2-phenylindole) and propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). We have identified new analogs as a novel class of antiproliferative agents by a cell-based screening method. All compounds inhibited the growth of malignant cells in a dose-dependent manner. The IC?? of compounds 4 and 5 as the two most potent analogs was determined as 122.4 and 106.7 μM in HeLa cells, respectively. Compounds 4 and 5 induced a sub-G1 peak in the flow-cytometry histogram of treated cells, compared to control, indicating that apoptotic cell death is involved in compound 4- and 5-induced toxicity. In conclusion, compounds 4 and 5 exert cytotoxic effects in different cancer cell lines in which apoptosis plays an important role. Thus, compounds 4 and 5 could be considered as potential chemotherapeutic agents.