Ocular Toxicity of Ethambutol During Both Intensive and Continuation Phases of Anti-Tubercular Therapy in Children

Objective: The study was conducted to evaluate the ocular toxicity of ethambutol given in both intensive and continuation phases of treatment in children with drug-sensitive tuberculosis. Methods: A prospective study of 94 eyes from 47 patients receiving an ethambutol-containing regimen was conducted between 1 December, 2018 and 31 August, 2020. Visual acuity, visual field, visual evoked response (VER), contrast sensitivity, colour perception, and retinal nerve fiber layer (RNFL) thickness [using optical coherence tomography (OCT)] were tested for each patient before, during, and after the treatment. Results: On follow-up, visual acuity, color vision, contrast sensitivity, fundus, and visual fields were not affected in any of the patients. There was no statistically significant increase in the mean latency of the P(100) wave at any point in time. On OCT, no significant loss of mean RNFL thickness was detected. Conclusions: Ethambutol is safe to use up to a dose of 20 mg/kg/day throughout the entire course of anti-tubercular therapy in children with drug-sensitive tuberculosis

Acremonium keratitis: Risk factors, clinical characteristics, management, and outcome in 65 cases

Purpose: To study the risk factors, clinical presentation, management options, and outcomes in cases of culture?proven Acremonium keratitis. Methods: Medical and microbiology records of culture?proven Acremonium keratitis from Jan 2007 to Dec 2019 at a tertiary eye care center were reviewed. Details of clinical findings on each visit and operating notes were reviewed from the medical records. All cases were subjected to corneal scraping at the first visit for microbiological investigation consisting of direct smear examination and culture. Topical natamycin 5% was the mainstay of medical treatment. Surgical treatment was considered for nonresponding patients. Results: During the 13?year study period, 65 cases of culture?proven Acremonium keratitis were identified out of 1605 cases of fungal keratitis. Trauma was the most common predisposing factor in 32 cases (49.2%). The average area of the corneal stromal infiltrate was 24.8 mm2 at the initial presentation. Hypopyon at the time of presentation was evident in 28 (43.1%) cases. Staphylococcus spp. was the most common (n = 22, 33.8%) organism coexistent with Acremonium. Direct microscopy of corneal scraping was positive for fungal filaments in 57/65 (87.6%) cases. Medical management alone was given in 44 patients (67.6%). Age (>50 years) and treatment delay (>15 days) were found to be independent risk factors for the poor final visual outcome (VA <20/60). Conclusion: When treated early, Acremonium keratitis responds well to medical therapy with currently available topical antifungals. However, advanced and nonresponding cases require surgical intervention for resolution of the infection

The retinal vascular growth rate in babies with retinopathy of prematurity could indicate treatment need

Purpose: To analyze the weekly rate of retinal vascular growth in treatment?na飗e babies with various stages of retinopathy of prematurity (ROP) and validate if this could be a predictor of treatment need. Methods: Retrospective review of medical charts and retinal images of babies with various stages of ROP. The images were enhanced using red?green image enhancement software. Using the length of the horizontal disc diameter (DD) of each eye, the vessel growth was measured from the disc margin up to the vessel tip in fixed quadrants. The rate of vessel growth was the ratio of vessel length to the number of weeks it took to reach this length. The babies were divided into treatment warranting ROP (group 1), low?risk pre?threshold (type II) ROP (group 2,), and no?ROP (group 3) for analysis. The 搉o?ROP� group acted as normal control. Group 1 was further subdivided into 1A (threshold ROP), IB (aggressive posterior ROP), 1C (hybrid ROP), and ID (high?risk pre?threshold ROP). Results: Out of 436 eyes, groups 1, 2, and 3 had 238, 108, and 90 eyes, respectively. The mean rate of vascular outgrowth along with 95% confidence interval (CI) was 0.490 [0.487,0.520], 0.612 [0.599, 0.638], and 0.719 [0.703, 0.740] DD/week, respectively, for babies with 搕reatment warranting,� 搇ow risk pre?threshold� and 搉o ROP� groups, respectively. In our estimate, more than 80% of eyes with a vessel growth rate of 0.54 DD/week or less required treatment. Conclusion: A rate of retinal vascular growth less than 0.54 DD/week can be used to determine treatment requirements in babies with ROP

Evidence of dengue virus in eviscerated specimens of panophthalmitis secondary to dengue fever: A possible cause-effect phenomenon

Purpose: To report a retrospective series of three cases of infectious panophthalmitis post?dengue fever with ex vivo confirmation of dengue virus ribonucleic acid (RNA) in the tissues of the eye. Methods: Four eyes of three patients, who were diagnosed with panophthalmitis following dengue fever and who underwent evisceration, were included. All demographic and clinical data were recorded. The eviscerated samples were subjected to direct microscopy, culture for bacteria, fungi, and parasites, and molecular virology (dengue virus [DENV] NS1?specific reverse transcription loop?mediated isothermal amplification (RT?LAMP) assay). Results: The time from the development of dengue fever to the occurrence of ocular symptoms was 4.33 ± 1.15 (median 5) days. DENV NS1 RNA, suggestive of the presence of the dengue virus, was confirmed in all evisceration specimens (uveal tissue, cornea). All the patients recovered completely from dengue fever and on follow?up had healthy eviscerated sockets. Conclusion: Demonstration of the DENV RNA in the eviscerated specimens of panophthalmitis following dengue fever implicates the DENV in the pathophysiology of the ocular infection.

Rescue of photoreceptor with human mesenchyme stem cell and human mesenchyme stem cell expressing erythropoietin in total degeneration of retina animal model

Purpose: This study aimed to investigate the efficacy of human?derived umbilical cord mesenchymal stem cells (HDUMSC) and human?derived umbilical cord mesenchymal stem cells expressing erythropoietin (HDUMSC?EPO) to rescue total degenerated retina in a rat model. Methods: The study included four treatment groups, namely negative control using normal saline (HBSS) injection, positive control using sodium iodide 60 mg/kg (SI), SI treated with HDUMSC, and SI treated with HDUMSC?EPO given via subretinal and intravenous routes, to test the efficacy of retinal regeneration following SI?induced retinal degeneration. Retinal function in both phases was tested via electroretinography (ERG) and histological staining examining the outer nuclear layer (ONL). Results: There was a statistically significant result (P < 0.05) in the SI treated with HDUMSC?EPO only when comparing day 11 (mean = 23.6 ?v), day 18 (mean = 25.2 ?v), day 26 (mean = 26.3 ?v), and day 32 (mean = 28.2 ?v) to the b?wave ERG on day 4 rescue injection day (mean = 12.5 ?v). The SI treated with HDUMSC?EPO showed significant improvement in b?wave ERG readings in the Sprague–Dawley (SD) rat but did not restore baseline readings prior to degeneration (day 0). Both treated groups’ ONL thicknesses did not show significant changes compared to the negative control group (HBSS) following rescue therapy. Conclusion: Total retinal degeneration following intravenous SI injection was observed at 60 mg/kg. SI treated with HDUMSC and HDUMSC?EPO showed no regenerative potential compared to baseline in SI?induced total retina degeneration on ERG or histology, whereas SI treated with HDUMSC?EPO group showed a substantial increase in b?wave ERG amplitude over time

Early changes in host and donor lenticule thickness after Descemet stripping endothelial keratoplasty

Purpose: To analyze the early changes in host and donor lenticule thickness after Descemet Stripping Endothelial Keratoplasty (DSEK). Methods: DSEK was performed on 32 eyes of 31 patients. Pre? and post? operative slit lamp examination and anterior segment Optical Coherence Tomography (OCT) was done on day?1, day?7, 1 month, and 3 months. Results: There were significant changes in host, lenticule, and total corneal thicknesses between day?1 and day?7, and day?7 and 1 month. There were significant changes in host thickness and total corneal thickness between 1 month and 3 months. Thickness changes were significant between day?1 and day?7, and 1 month and 3 months for thick and thin host, respectively, whereas these changes were observed both for thick and thin host between day?7 and 1 month. Similarly, significant changes were observed between day?7 and 1 month, and day?7 and 1 month in thin lenticule whereas in case of thick lenticule, it was observed till the 3 months follow?up period. There was a significant improvement in visual acuity till the 3 months follow?up period. No significant correlation was observed between visual acuity and host and lenticule thickness. Conclusion: The thicknesses of host and lenticule decrease continuously. Lenticule thickness stabilizes before host. Thinner cornea stabilizes earlier compared to thicker cornea

THYROID PROFILE AMONG PREGNANT WOMEN ATTENDING AT MATERNITY AND CHILDREN HOSPITAL, QASSIM.

Introduction: Thyroid gland that regulate the body's metabolic rate controlling heart, muscle and digestive function, brain development and bone maintenance. Thyroid problems are quite common in pregnancy and can be affected both maternal and foetal, also can lead to various adverse outcomes. Methods: This was a cross-sectional study conducted at Maternity and Children Hospital, Qassim, Saudi Arabia. Study participants data included from July 2020 to March 2021 and included all the women attending the antenatal clinics subjected for thyroid function test. The sample size of 195 and analyzed for thyroid hormone pro?le which included free T3, free T4, TSH and haemoglobin (HGB) levels. The data were retrieved from the electronic ?les of pregnant women at Maternity and Children Hospital and appropriate statistical tests were applied. Results: In the current study, mean age and standard deviation observed in the study population was 34.87 ± 5.67 and 53.8% were in the age group of 31-40 years age group, sub clinical hypothyroidism was 9.2%. Among the pregnant women, about 16.4% were Diabetes and 8.7% were having gestational Diabetes. Mean haemoglobin and standard deviation was 11.24 ± 1.29. There was statistically signi?cant association was observed between personal history of thyroid disease versus classi?cation of thyroid disease in the study population. (87.4% and 15%, P<0.001). Conclusions: Based on the study ?ndings, increase prevalence of Diabetes and Gestational Diabetes was more among the pregnant thyroid people. Relatively Hypothyroid, hyperthyroid and sub clinical hypothyroidism was more in the present study. Nearly close to half (44%) of pregnant women thyroid status was only controlled. Still, there is health education and counselling sessions periodically required to the women visiting at MCH hospital with thyroid disorder

The role of basolateral amygdala orexin 1 receptors on the modulation of pain and psychosocial deficits in nitroglycerin-induced migraine model in adult male rats

Background@#Migraine headaches have been associated with sensory hyperactivity and anomalies in social/emotional responses. The main objective of this study was to evaluate the potential involvement of orexin 1 receptors (Orx1R) within the basolateral amygdala (BLA) in the modulation of pain and psychosocial dysfunction in a nitroglycerin (NTG)-induced rat model of migraine. @*Methods@#Adult male Wistar rats were injected with NTG (5 mg/kg, intraperitoneal) every second day over nine days to induce migraine. The experiments were done in the following six groups (6 rats per group): untreated control, NTG, NTG plus vehicle, and NTG groups that were post-treated with intra-BLA microinjection of Orx1R antagonist SB-334867 (10, 20, and 40 nM). Thermal hyperalgesia was assessed using the hot plate and tail-flick tests. Moreover, the elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behaviors. The animals’ sociability was evaluated using the three-chamber social task. The NTG-induced photophobia was assessed using a light-dark box. @*Results@#We observed no change in NTG-induced thermal hyperalgesia following administration of SB-334867 (10, 20, and 40 nM). However, SB-334867 (20 and 40 nM) aggravated the NTG-induced anxiogenic responses in both the EPM and OF tasks. The NTG-induced social impairment was overpowered by SB-334867 at all doses. Time spent in the dark chamber of light-dark box was significantly increased in rats treated with SB-334867 (20 and 40 nM/rat). @*Conclusions@#The findings suggest a role for Orx1R within the BLA in control comorbid affective complaints with migraine in rats.

Evaluation of drug utilisation pattern and cost associated with diabetes mellitusType 2 management in Saudi Arabia

Abstract Diabetic mellitus is an emerging disease in Saudi Arabia. In this regard, a cross-sectional retrospective study was conducted to evaluate drug utilization pattern and the cost associated with non-insulin-dependent diabetes mellitus disease management in Saudi Arabia. Data retrieved from the electronic pharmacy records during the last one year were employed in this study. World Health Organization (WHO) Defined Daily Dose (DDD) method was employed to compute the daily price of each oral hypoglycaemic agent. The American Diabetes Association (ADA) guidelines and protocols were used to evaluate the level of adherence. A total of 17057 patients were enrolled in the study. Out of the 17057 patients enrolled in the study, 60.06 % (10246) were males and the rest females. In monotherapy, biguanides (metformin) were the most recommended and utilised drugs among 5673 patients (33.25%). The most commonly used drug combination was found to be sitagliptin+metformin (1754 units). The cost per unit dose was highest for liraglutide (A10BJ02) 258.32SR (68.79USD), and lowest for metformin (A10BA02) 0.49SR (0.13 USD). Metformin was the choice drug for the diabetes patients; biguanides (metformin) and DPP-4 (sitagliptins) were the most familiar established dose combination employed. Generic drugs should be used in order to reduce overall cost.

Phytohormone abscisic acid boosts pentobarbital-induced sleep through activation of GABA-A, PPARß and PPARγ receptor signaling / O fito-hormônio ácido abscísico estimula o sono induzido por fenobarbital por meio de ativação da sinalização de receptores GABA-A, PPARß e PPARγ

ABSTRACT Background: Sleep disorders induce anxiety and forgetfulness and change habits. The chemical hypnotic drugs currently used have serious side effects and, therefore, people are drawn towards using natural compounds such as plant-based healing agents. Abscisic acid (ABA) is produced in a variety of mammalian tissues and it is involved in many neurophysiological functions. Objective: To investigate the possible effect of ABA on pentobarbital-induced sleep and its possible signaling through GABA-A and PPAR (γ and β) receptors, in male Wistar rats. Methods: The possible effect of ABA (5 and 10 µg/rat, intracerebroventricularly) on sleep onset latency time and duration was evaluated in a V-maze model of sleep. Pentobarbital sodium (40 mg/kg, intraperitoneally) was injected to induce sleep 30 min after administration of ABA. PPARβ (GSK0660, 80 nM/rat), PPARγ (GW9662, 3 nM/rat) or GABA-A receptor (bicuculline, 6 µg/rat) antagonists were given 15 min before ABA injection. Diazepam (2 mg/kg, intraperitoneally) was used as a positive control group. Results: ABA at 5 µg significantly boosted the pentobarbital-induced subhypnotic effects and promoted induction of sleep onset in a manner comparable to diazepam treatment. Furthermore, pretreatment with bicuculline significantly abolished the ABA effects on sleep parameters, while the amplifying effects of ABA on the induction of sleep onset was not significantly affected by PPARβ or PPARγ antagonists. The sleep prolonging effect of ABA was significantly prevented by both PPAR antagonists. Conclusions: The data showed that ABA boosts pentobarbital-induced sleep and that GABA-A, PPARβ and PPARγ receptors are, at least in part, involved in ABA signaling.

RESUMO Introdução: Os distúrbios do sono induzem a ansiedade e esquecimento e mudam hábitos. Os medicamentos hipnóticos químicos utilizados atualmente têm efeitos colaterais graves e, portanto, as pessoas são atraídas para o uso de compostos naturais, como agentes de cura à base de plantas. O ácido abscísico (ABA) é produzido em uma variedade de tecidos de mamíferos e está envolvido em muitas funções neurofisiológicas. Objetivo: Investigar o possível efeito do ABA no sono induzido por pentobarbital e sua possível sinalização por meio dos receptores GABA-A e PPAR (γ e β), em ratos Wistar machos. Métodos: O possível efeito do ABA (5 e 10 µg/rato, intracerebroventricularmente) no tempo de latência e duração do início do sono foi avaliado em um modelo de labirinto em V de sono. Pentobarbital sódico (40 mg/kg, intraperitonealmente) foi injetado para induzir o sono 30 minutos após a administração de ABA. PPARβ (GSK0660, 80 nM/rato), PPARγ (GW9662, 3 nM/rato) ou antagonistas do receptor GABA-A (bicuculina, 6 µg/rato) foram administrados 15 minutos antes da injeção de ABA. Diazepam (2 mg/kg, intraperitonealmente) foi utilizado como grupo de controle positivo. Resultados: ABA a 5 µg aumentou significativamente os efeitos sub-hipnóticos induzidos por pentobarbital e promoveu a indução do início do sono de forma comparável ao tratamento com diazepam. Além disso, o pré-tratamento com bicuculina aboliu significativamente os efeitos do ABA nos parâmetros do sono, ao passo que os efeitos amplificadores do ABA na indução do início do sono não foram significativamente afetados pelos antagonistas do PPARβ ou PPARγ. O efeito de prolongamento do sono do ABA foi significativamente prevenido por ambos os antagonistas do PPAR. Conclusões: Os dados mostraram que o ABA estimula o sono induzido por pentobarbital e que os receptores GABA-A, PPARβ e PPARγ estão, pelo menos em parte, envolvidos na sinalização ABA.

Evaluation of the growth medium of a new ice-nucleating-active Pseudomonas: A response surface methodology approach

Aims@#Attention to ice nucleation proteins has increased for more than two decades. Ice nucleation proteins have been utilized for artificial snow-making known as Snowmax™, cryopreservation of tissues and cells, and cloud condensation nuclei. There is a direct relationship between bacterial growth and ice nucleation activity. Therefore, the optimization of the culture medium seems necessary.@*Methodology and results@#The effect of different carbon and nitrogen sources on the growth of a new native Pseudomonas sp. IRL.INP1 was evaluated by using fractional factorial design, the path of the steepest ascent experiment and central composite design. Ice nucleation activity, biomass and whole-cell protein were identified afterward. The model predicted by response surface methodology indicated that the maximum bacterial growth was observed when sucrose, ammonium sulfate [(NH4)2SO4] and manganese (II) (Mn2+) were utilized at 12.46 g/L, 321.97 mg/L and 938.09 µM, respectively. Also, 1.10 g/L biomass and 0.85 µg/µL whole-cell proteins were gained, and the isolate showed ice nucleation activity 31 sec sooner after optimization.@*Conclusion, significance and impact of study@#Ice nucleation proteins are growth-dependent and the growth condition optimization leads to higher bacterial cells growth. Therefore, best bacterial growth was obtained when proper carbon and nitrogen sources were used, and ice nucleation activity was observed in shorter time. This is the first study concerning ice nucleation activity optimization using different carbon and nitrogen sources.

Catalytic and structural effects of flexible loop deletion in organophosphorus hydrolase enzyme: A thermostability improvement mechanism

Thermostability improvement of enzymes used industrially or commercially would develop their capacity andcommercial potential due to increased enzymatic competence and cost-effectiveness. Several stabilizing factorshave been suggested to be the base of thermal stability, like proline replacements, disulfide bonds, surface looptruncation and ionic pair networks creation. This research evaluated the mechanism of increasing the rigidity oforganophosphorus hydrolase enzyme by flexible loop truncation. Bioinformatics analysis revealed that themutated protein retains its stability after loop truncation (five amino acids deleted). The thermostability of thewild-type (OPH-wt) and mutated (OPH-D5) enzymes were investigated by half-life, DGi, and fluorescence andfar-UV CD analysis. Results demonstrated an increase half-life and DGi in OPH-D5 compared to OPH-wt.These results were confirmed by extrinsic fluorescence and circular dichroism (CD) spectrometry experiments,therefore, as rigidity increased in OPHD5 after loop truncation, half-life and DGi also increased. Based onthese findings, a strong case is presented for thermostability improvement of OPH enzyme by flexible looptruncation after bioinformatics analysis.

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial / 대한생식의학회지

Objective@#Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL. @*Methods@#Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n=20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment. @*Results@#Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of PRM1, PRM2, and the PRM1/PRM2 ratio after treatment. @*Conclusion@#Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases.

Epidemiological, molecular characterization and risk factors of human brucellosis in Iran

Objective: To determine epidemiological, molecular characterization, and potential risk factors of human brucellosis. Methods: This descriptive study was carried out in the clinical setting in Iran between 2017 and 2018. A total of 297 participants enrolled in the study. The sample size was calculated based on the occurrence rate of brucellosis in different areas. Patients were assessed using serological tests and conventional culture methods. Phage and multiplex PCR methods typed all of Brucella isolates. Potential risk factors of disease were determined. Results: A total of 141 of 297 (47.5%) Brucella strains were isolated and all of them were detected as Brucella melitensis biovar 1. Based on serologic titers, high culture positivity was recorded at 1/640 titer (P< 0.006). The risk factors for brucellosis were patients older than 40 years (OR=2.23, 95%CI: 1.4-3.55, P=0.001), animal keeper (OR=7, 95%CI: 1.51-32.41, P=0.005), housewife (OR=8.76, 95%CI: 1.85-41.37, P=0.002), farmer (OR=6.42, 95%CI: 1.21-33.97, P=0.019), and contact with animal (OR=1.31, 95%CI: 0.60-2.85, P=0.005). Conclusions: To the best of our knowledge, this is the first comprehensive report from Iran presenting the detection of Brucella species by the multiplex PCR. Brucella melitensis biovar 1 is still the dominant causative agent in Iran. The consumption of unpasteurized dairy products, living in rural areas, and animal contact were risk factors of brucellosis.

The effectiveness of the national hepatitis B vaccination program 25 years after its introduction in Iran: a historical cohort study

ABSTRACT Introduction: Hepatitis B virus (HBV) is responsible for one of the most common human viral infections. An estimated 257 million people are living with chronic HBV infection worldwide, and mortality has reached 900,000 deaths in recent years. In 2001, the World Health Organization reported a prevalence of chronic hepatitis B infection in Iran between 2-7%. Objective: To assess the effect of the national HBV mass vaccination program after 25 years. Methods: A retrospective cohort study was conducted in vaccinated and unvaccinated people according to the year of birth. Blood samples were obtained from each enrolled person and data about demographic variables, and medical and vaccination history were collected using a standardized questionnaire. Persons were considered uninfected if they were negative for both HBsAg and anti-HBc. Also, Vaccine effectiveness was measured by calculating the risk of disease among vaccinated and unvaccinated persons and defining the percentage risk reduction of infection in the vaccinated group. Results: A total of 2720 persons were interviewed. The rate of HBV breakthrough infection among the vaccinated group was significantly lower than in unvaccinated group. One hundred ninety-four cases with positive HBV markers of infection were identified. The risk ratio of HBV infection was 0.71, 95% CI: 0.54-0.94 (vaccinated/unvaccinated). The estimated vaccination effectiveness against Hepatitis B infection was 29% (95% CI: 6%-46%). Conclusions: Iran has successfully combined hepatitis B vaccination into regular immunization programs. The WHO goal of reducing HBsAg prevalence to an equivalent of 1% by 2020 has been reached. With respect to vaccination effectiveness and low prevalence of the disease in the country, catch-up hepatitis B vaccination programs for adolescents can guarantee the immunity of the population.

Evaluating the olfactory dysfunction and cognitive deficits induced by intracerebroventricular injection of Amyloid beta (1–42) in female C57BL/6 mice

Amyloid-β (Aβ) is a key pathological hallmark of Alzheimer's disease (AD), the most common form of dementiamajorly occurring in the geriatrics. Aβ accumulation is observed in the brains of AD patients and is reported toproduce long-term effects on cognitive functions leading to neurodegeneration, and subsequently, to AD. Olfactorydeficits are reported in AD and are proposed to be another consequence of these accumulations. The present studywas performed to primarily investigate the olfactory behavior and neurochemical changes in olfactory bulb uponintracerebroventricular (i.c.v) injection of Aβ (1–42) in female C57BL/6 mice. The study also assessed the cognitivechanges of i.c.v injected animals and recorded the subsequent changes in their hippocampus. All behavioral andneurochemical variations were noted separately on 7th, 17th, and 28th day after i.c.v injection. Results from thebehavioral analysis indicated prominent olfactory deficit from the 7th day. Reactive oxygen species levels increasedin both the tissues after Aβ injection. Neurotransmitter data showed that pathological accumulation of Aβ increasesglutamate levels in bulb and hippocampus. Additionally, histopathological evidence supported the neurochemical data.Data from the present study confirmed an olfactory dysfunction associated with AD and reported the neurochemicalchanges leading to these deficits in a non-transgenic model.

Efficacy and Feasibility of Adding Induction Chemotherapy to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Phase II Clinical Trial

PURPOSE: Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer. METHODS: This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3–4 and/or N1–2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45–50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary end-points, respectively. RESULTS: The study participants included 37 males and 17 females, with a median age of 59 years (range, 20–80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent. CONCLUSION: The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.

Cytotoxic effect of methanolic extracts of Fritillaria imperialis bulbs and Eryngium caucasicum leaves on hepatoma and colon cancer cells

Objective: To evaluate antitumor activities of Fritillaria imperialis and Eryngium caucasicum methanolic extracts on human hepatoma (HepG2) and colon cancer (HCT116) cell lines in comparison to human foreskin fibroblasts as the normal cells. Methods: Methanolic extracts of Fritillaria imperialis and Eryngium caucasicum were prepared by the maceration method. The effect of the extracts at various concentrations (100, 200, 400, 600, and 800 μg/mL) on cell survival was evaluated using the MTT method. Besides, fluorescence staining was used to evaluate death patterns of the cells. Results: MTT assay showed that Fritillaria imperialis significantly decreased the viability of all cell lines after 24 and 48 hours of treatments. However, Eryngium caucasicum extract did not show any significant cytotoxicity effect on the cell lines. Fluorescence staining revealed that Fritillaria imperialis induced apoptosis of HCT116 cells at 550 μg/mL. Conclusions: Fritillaria imperialis extract has antiproliferative and cytotoxic effects on HCT116 and HepG2 cancer cells and therefore, may serve as an anticancer agent.

Trigonella foenum-graecum seed extract modulates expression of lipid metabolism-related genes in HepG2 cells

Objective: To investigate anti-dyslipidemic effects of hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile on HepG2 cell line. Methods: HepG2 cells were treated with hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat. IC20 was calculated using the MTT method. The cells were then pre-treated with IC20 concentrations for 24 and 48 h. Real time PCR was employed to measure expression of liver X receptor alpha (LXRα), sterol regulatory element-binding protein-1C (SREBP-1C), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), fibroblast growth factor 21 (FGF21), peroxisome proliferator-activated receptor gamma (PPARγ), and low-density lipoprotein receptor (LDLR). Results: The results showed that LXRα (P=0.003, P<0.001), SREBP-1C (P<0.001, P<0.001), ACC (P=0.002, P=0.006), and FAS (P<0.001, P<0.001) were downregulated significantly, while FGF21 (P<0.001, P<0.001), PPARγ (P=0.004, P<0.001), and LDLR (P<0.001, P<0.001) were upregulated significantly in HepG2 cells treated with the IC20 of hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat in 24 and 48 h, respectively. Conclusions: Hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile significantly modulate the expression of some important lipid metabolism related genes, which is similar to orlistat. Trigonella foenum-graecum seed extract or its derivatives should be further investigated for their dyslipidemia effects and its complications.