Assessing the Prevalence and Risk Factors of Postpartum Depression: A Cross-Sectional Study Conducted in the Urban Areas of Ankuli in Southern Odisha.

Background Postpartum depression (PPD) is a complex mix of physical, emotional, and behavioral changes that happen in some women after giving birth. Objectives The aim of the study is to determine the prevalence of PPD using the Edinburgh Postnatal Depression Scale (EPDS) and evaluate the predisposing factors for PPD. Methodology The present observational study was conducted in the Department of Community Medicine, Maharaja Krushna Chandra Gajapati (MKCG) Medical College and Hospital, Brahmapur, Odisha, India from May 2022 to November 2022. Using the EPDS, participants were assessed for postnatal depression. Every subject additionally filled out a risk factor questionnaire covering important sociodemographic and obstetric parameters. The prevalence of an EPDS score of 12 or above is the primary outcome measure. Results The study encompassed 121 mothers, with 8.26% scoring above the depression cutoff of 12 and 6.61% falling within the borderline range. Notably, all mothers surpassing the cutoff were from joint families, contrasting with those from nuclear families. A predominant portion of the depressive group was in their 20s, while the borderline group primarily consisted of mothers in their 30s. Urban residency and government hospital care were universal among the samples. Mode of delivery showed significance, with a higher prevalence of PPD observed among those who underwent a lower segment cesarean section. Additionally, maternal age, anemia, mode of delivery, educational status, adverse life events, and lack of partner support significantly correlated with depression scores. Notably, maternal age emerged as the most influential factor, followed by anemia and mode of delivery. Spearman correlation analysis revealed moderate negative associations between various aspects of maternal depression and the ages of their babies, indicating that younger infants were associated with greater maternal distress. However, the correlation between feeling sad or miserable and the baby's age was negligible. These findings emphasize the multifaceted nature of PPD, highlighting the interplay between sociodemographic factors, maternal well-being, and infant age.

A Qualitative Analysis of Urbanization and Menstrual Health Among Young Women.

This qualitative study, grounded in theory, employed inductive coding for analysis, focusing on menstrual health among urban women aged 10-25. The research aims to explore the menstrual health status, practices, and beliefs of participants. The research delves into the impact of recent government initiatives on menstrual health and assesses the role of urbanization in shaping evolving menstrual health practices among young girls. Employing in-depth qualitative methods such as interviews and focus group discussions, the study seeks a comprehensive understanding of participants' experiences and perceptions related to menstrual health. The dynamics of women's menstrual experiences are significantly influenced by urbanization, heightened exposure to social media, evolving lifestyles, and government initiatives like the distribution of menstrual products in schools and the enhancement of water, sanitation, and hygiene (WASH) facilities in government institutions. Positive shifts have been observed, including reduced restrictions on menstruating individuals, enhanced access to affordable hygiene products, and improved disposal facilitated by municipal garbage collection services. However, notable gaps persist in basic knowledge about menstruation, hygienic practices, effective interpersonal communication with schoolteachers or community health care workers, and compliance with government programs promoting weekly iron-folic acid supplementation and biannual Albendazole intake, calling for substantial improvement.

A Study to Describe the Pattern of Cutaneous Adverse Effects of COVID-19 Vaccines (Covishield and Covaxin).

Background: Vigorous administration of COVID-19 vaccines to tackle the ongoing pandemic has led to increasing research on adverse effects including both systemic and cutaneous. Objective: A prospective observational study to delineate the cutaneous adverse effects of two vaccines, namely Covishield and Covaxin, administered in two doses in northern India. Materials and Methods: The study was conducted in a tertiary hospital in northern India wherein patients were asked to report voluntarily any cutaneous adverse effects after COVID-19 vaccination to the dermatology department. The data were collected using excel sheets and later analyzed taking into consideration the age, vaccine types, and duration of onset of adverse effects. Results: Of the 19,672 vaccination jabs, 296 (1.5%) developed cutaneous adverse effects of which the incidence was higher in Covishield vaccine group compared to Covaxin vaccine group. The incidence of side effects was more with the first dose of either vaccine compared to the second dose. All the side effects were benign and were managed symptomatically or were self-limiting. Limitations: The number of vaccine recipients was limited and there was a considerable overlap of adverse effects with both vaccines. Voluntary reporting of cases is not an accurate representation of the scale of patients with adverse effects. Conclusion: Rampant administration of vaccines along with widespread advertisement of vaccine-induced side effects via social media has created apprehension in the general population. This warrants studies improving awareness about the most vital preventive measure available to halt and eventually end the COVID-19 pandemic.

In silico multi-epitope Bunyumwera virus vaccine to target virus nucleocapsid N protein.

BACKGROUND: Bunyumwera virus can cause 82% mortality in humans currently with no vaccine or drugs for treatment. We described an in silico multi-epitope vaccine targeting Bunyumwera virus nucleocapsid N-protein and predicted B and T cell epitopes for immunogenicity, allergenicity, toxicity, and conservancy. For creating the most potent immunological response possible, docking epitopes with HLA alleles are chosen to screen them. The 3D vaccination was docked with the Toll-like receptor-8 using molecular dynamic simulations. To ensure production efficiency, the vaccine sequence was further cloned in silico in a plasmid pIB2 vector. For efficacy and safety, results must be supported in vitro and in vivo. RESULTS: The vaccine was cloned to enable expression and translation in a plasmid vector pIB2. It was expected to be antigenic, non-allergenic, and have a high binding affinity with TLR-8 in silico cloning. This multi-epitope vaccination may stimulate both innate and adaptive immunity. CONCLUSION: The vaccine developed in this work was based on the nucleocapsid N-protein of the Bunyumwera virus and was created using a reverse vaccinology method. Further experimental validation is required to assess the vaccine's therapeutic effectiveness and immunogenicity.

Resurgence of syphilis, the great imitator.

Syphilis, one of the earliest diseases to be discovered in humans, still remains an enigma when it comes to its myriad manifestations and changing epidemiological profiles. There has been a surge in cases in the last few decades due to various factors. The human immunodeficiency virus (HIV) epidemics, global travel, increased incidence of male to male sexually transmitted diseases, online relationships culminating in casual sex are few of the important factors. Increased awareness could also be a factor for increased diagnosis. The multitude of clinical features especially when it comes to secondary syphilis and the rare tertiary manifestations, which can mimic various systemic disorders still pose a diagnostic challenge to the best of venereologists and physicians. This review aims to discuss the causes of resurgence in syphilis and few recent developments in pathogenesis, which could have led to this resurgence.

The Use of Screening Tools for Cardiovascular Risk Assessment in Psoriasis - A Case- Control Study.

BACKGROUND: Psoriasis is a common, T-cell-mediated disease, affecting 0.44-2.8% of the general population in India. It is associated with a higher risk of cardiovascular disease possibly due to chronic inflammation. Those patients with severe psoriasis are at a higher risk of death due to cardiovascular disease. The use of scoring tools may help the care providers to assess cardiovascular risks in these patients. AIMS: The aim of this study was to assess the cardiovascular risks in patients with severe psoriasis using the commonly used risk-assessment tools (Framingham risk score [FRS] and Pooled cohort equations [PCE]) and to understand the utility of these tools in practice. METHODS: It is a case-control study performed in the dermatology outpatient department of a tertiary care center during the study period from January to December 2020. Consenting adults with chronic plaque psoriasis and psoriasis area and severity index (PASI) more than 10 were included in the study. The FRS and PCE risk scores were calculated for the patients and age- and sex-matched healthy controls. RESULTS: A total of 213 patients were assessed and 30 patients were excluded. Of the 183 patients, 152 patients were assessed using FRS and 135 patients using PCE. Equal number of age- and sex-matched healthy controls were also assessed. The mean age of the patients assessed using the FRS and PCE was 47 ± 10.9 and 52.84 ± 8.9 years, respectively. The mean age of the controls was 45.52 ± 8.7 and 51.76 ± 8.1 years in the FRS and PCE groups, respectively. The male to female ratio was 1.92:1 and 2:1 in the FRS and PCE risk-score groups, respectively. The mean PASI score was 16.45 ± 7.88 and 15.6 ± 7.6 in the two groups, respectively. The 10-year risk estimate using FRS in the patients ranged from 0 to 26.9%. The mean and median estimates were 4.95 ± 5.7 and 2.8%, respectively, while 2.65 ± 4.7 and 0.8% in the controls (P = 0.001). The 10-year risk estimate in the patients using the PCE risk score ranged from 0.3 to 39.6%. The mean and median estimate in the patients was 8.17 ± 9.9 and 5.2%, respectively while they were 5.68 ± 7.5% and 2.6% in the controls (P = 0.024). The agreement between the FRS and PCE was found to be poor (Ϗ, 0.049). There was no statistically significant correlation of PASI to either the PCE risk score (P = 0.498) or FRS (P = 0.630). LIMITATIONS: A small sample size, and study in a tertiary care center may have resulted in sampling bias. CONCLUSION: Psoriasis is associated with a higher risk of cardiovascular disease. These tools may help a dermatologist in the primary prevention of cardiovascular disease. It can also help in the awareness of the increased risk of cardiovascular disease in patients.

Antiproliferative and ROS Regulation Activity of Photoluminescent Curcumin-Derived Nanodots.

Recently, various types of nanomaterials have been employed to design delivery vehicles for curcumin to address the problems of poor bioavailability, low aqueous solubility, and rapid metabolism. The present study focuses on a direct one-pot synthesis of curcumin-derived nanoparticles and exploits their potential therapeutic properties in cancer cells in vitro without additional delivery vehicles. The nanoparticles, named E-Curc-dots, are synthesized using three precursor molecules, ethylenediamine (EDA), curcumin, and citric acid. The structure, composition, and physichemical properties of the nanodots are characterized and identified by employing spectroscopic and microscopic techniques. The as-synthesized E-Curc-dots exhibit bright blue photoluminescence due to the incorporation of nitrogen from the EDA precursor molecule. The characterization studies show a uniform distribution of dots with an average size of 4.6 ± 1.7 nm and, notably, that the dots retain some of the major characteristics of native curcumin with much improved water solubility and bioavailability. The E-Curc-dots show antioxidation activity at low concentrations (<0.08 mg/mL) with low levels of reactive oxygen species (ROS) generation, i.e., 82% of the ROS level in cells without treatment for A549 cells; however, at high concentrations, the nanodots exhibit a pro-oxidant effect on both the cancer cells (A549) and normal cells (EA.hy926) by inducing more ROS generation and dose-dependent cytotoxicity. The E-Curc-dots demonstrate higher cytotoxicity toward cancer cells compared to native curcumin at a lower concentration. The results indicate the efficacy of E-Curc-dots as an antiproliferative and ROS regulator with the ability of cellular bioimaging.

High Quantum Yield Fluorescent Carbon Nanodots for detection of Fe (III) Ions and Electrochemical Study of Quenching Mechanism.

Carbon nanodots (CNDs) offer potential applications in photocatalysis, optoelectronics, bio-imaging, and sensing due to their excellent photoluminescence (PL) properties, biocompatibility, aqueous solubility, and easy functionalization. Recent emphasis on CNDs in the selective detection of metal ions is due to the growing concern for human and environmental safety. In this work, two types of fluorescent carbon nanodots (CNDs) are synthesized economically from ethylene diamine (E-CNDs) or urea (U-CNDs) in a single step microwave process. The as-prepared CNDs exhibit excellent PL at an excitation wavelength of 350 nm with a quantum yield of 64% for E-CNDs and 8.4% for U-CNDs with reference to quinine sulfate. Both E-CNDs and U-CNDs demonstrate high selectivity towards Fe (III) ions among different metal ions, by fluorescence quenching in a dose dependent manner. The limit of detection of E-CNDs and U-CNDs is observed to be 18 nM and 30 nM, respectively, in the linear response range of 0-2000 µM with a short response time (seconds). The CNDs detect Fe (III) ions in tap water and serum sample with no spiking and the recovery was ~100% with the Fe (III) samples. Cellular internalization studies confirm the localization of the CNDs and the optical imaging sensing of Fe (III) ions inside living cells. A charge transfer fluorescence quenching mechanism, specifically between the CNDs and Fe (III), is proposed and examined using cyclic voltammetry. The overall characteristics of the E-CNDs provides a potential sensing platform in highly sensitive and selective detection of Fe (III) ions.

Novel microwave synthesis of near-metallic copper sulfide nanodiscs with size control: experimental and DFT studies of charge carrier density.

A simple unprecedented microwave synthesis of size controllable copper sufide (CuS) nanodiscs is reported. The experimental results and density functional theory (DFT)-calculated results show charge carrier densities on the order of 1021 cm-3 with an effective mass of 0.3m e, resulting in near-metallic properties.

Design of Curcumin Loaded Carbon Nanodots Delivery System: Enhanced Bioavailability, Release Kinetics, and Anticancer Activity.

Despite the potential health benefits of curcumin, such as antioxidant, anticancer, anti-inflammatory, and antimicrobial properties, its usage is limited by poor bioavailability and low aqueous solubility. Nano-formulations of curcumin have gained a lot of attention due to their increased bioavailability, solubility, circulation times, targeted specificity, decreased biodegradation, better stability, and improved cellular uptake. The current study aimed to enhance the bioavailability of curcumin using carbon nanodots (CNDs) as loading vehicles to deliver curcumin due to their excellent biocompatibility, aqueous solubility, and photoluminescence properties. Two types of CNDs (E-CNDs and U-CNDs) were used for curcumin loading and characterized for particle size, morphology, loading capability (measured as adsorption efficiency and loading capacity), stability, photoluminescence properties, in vitro drug release studies, cellular uptake, and anticancer activity. The prepared curcumin-loading CNDs (Curc-CNDs) displayed sizes around or below 10 nm with good stability. The Curc-E-CNDs demonstrated a curcumin adsorption efficiency of 91% in solution, while the Curc-U-CNDs have an adsorption efficiency of 82%. Both have a loading capacity of 3.4-3.8% with respect to the weight of the CNDs. Curcumin release followed a controlled sustained pattern that a total of 60% and 74% of curcumin was released at 72 h from Curc-E-CNDs and Curc-U-CNDs, respectively, in pH 5 buffer, and almost 90% was released in culture media within 96 h. Both of the Curc-CNDs were uptaken by cells and exhibited prominent cytotoxicity toward cancer cells. The results clearly depict the role of CNDs as efficient carriers for curcumin delivery with prolonged release and enhanced bioavailability, thereby improving the overall antitumor activity.

F8-IL10: A New Potential Antirheumatic Drug Evaluated by a PET-Guided Translational Approach.

Antibody fragment F8-mediated interleukin 10 (IL10) delivery is a novel treatment for rheumatoid arthritis (RA). F8 binds to the extra-domain-A of fibronectin (ED-A). In this study, in vivo biodistribution and arthritis targeting of radiolabeled F8-IL10 were investigated in RA patients, followed by further animal studies. Therefore, three RA patients (DAS28 > 3.2) received 0.4 mg of 30-74 megabecquerel [124I]I-F8-IL10 for PET-CT and blood sampling. In visually identified PET-positive joints, target-to-background was calculated. Healthy mice, rats, and arthritic rats were injected with iodinated F8-IL10 or KSF-IL10 control antibody. Various organs were excised, weighed, and counted for radioactivity. Tissue sections were stained for fibronectin ED-A. In RA patients, [124I]I-F8-IL10 was cleared rapidly from the circulation with less than 1% present in blood after 5 min. PET-CT showed targeting in 38 joints (11-15 per patient) and high uptake in the liver and spleen. Mean target-to-background ratios of PET-positive joints were 2.5 ± 1.2, 1.5 times higher for clinically active than clinically silent joints. Biodistribution of radioiodinated F8-IL10 in healthy mice showed no effect of the radioiodination method. [124I]I-F8-IL10 joint uptake was also demonstrated in arthritic rats, ∼14-fold higher than that of the control antibody [124I]I-KSF-IL10 ( p < 0.001). Interestingly, liver and spleen uptake were twice as high in arthritic than in healthy rats and were related to increased (∼7×) fibronectin ED-A expression in these tissues. In conclusion, [124I]I-F8-IL10 uptake was observed in arthritic joints in RA patients holding promise for visualization of inflamed joints by PET-CT imaging and therapeutic targeting. Patient observations and, subsequently, arthritic animal studies pointed to awareness of increased [124I]I-F8-IL10 uptake in the liver and spleen associated with moderate systemic inflammation. This translational study demonstrated the value of in vivo biodistribution and PET-CT-guided imaging in development of new and potential antirheumatic drugs'.

The folate receptor ß as a macrophage-mediated imaging and therapeutic target in rheumatoid arthritis.

Macrophages play a key role in the pathophysiology of rheumatoid arthritis (RA). Notably, positive correlations have been reported between synovial macrophage infiltration and disease activity as well as therapy outcome in RA patients. Hence, macrophages can serve as an important target for both imaging disease activity and drug delivery in RA. Folate receptor ß (FRß) is a glycosylphosphatidyl (GPI)-anchored plasma membrane protein being expressed on myeloid cells and activated macrophages. FRß harbors a nanomolar binding affinity for folic acid allowing this receptor to be exploited for RA disease imaging (e.g., folate-conjugated PET tracers) and therapeutic targeting (e.g., folate antagonists and folate-conjugated drugs). This review provides an overview of these emerging applications in RA by summarizing and discussing properties of FRß, expression of FRß in relation to macrophage polarization, FRß-targeted in vivo imaging modalities, and FRß-directed drug targeting.

Prophylactic and therapeutic activity of alkaline phosphatase in arthritic rats: single-agent effects of alkaline phosphatase and synergistic effects in combination with methotrexate.

Alkaline phosphatase (AP) is a gate-keeper of innate immune system responses by detoxifying inflammation triggering moieties released from endogenous and external sources. We examined whether AP's broad mechanism of action constitutes a safe therapeutic, either as single agent or combined with methotrexate (MTX), for chronic inflammatory disorders, for example, rheumatoid arthritis (RA). A rat model for RA was used with repeated intra-articular methylated bovine serum albumin (mBSA) injections in 1 knee ("arthritic" knee), with the contralateral knee serving as internal control. AP (200 µg, subcut) was administered before mBSA injections (prophylactic setting) or after arthritis induction (therapeutic setting) or combined with MTX (0.3 mg/kg or 1 mg/kg; intraperitoneally). As end point of treatment outcome, macrophage infiltration in knees, liver, and spleen was assessed by immunohistochemistry (ED1 and ED2 expression), immunofluoresence (macrophage marker folate receptor-ß [FRß]), and [18F]fluoro-polyethylene glycol-folate positron emission tomography (PET) (macrophage imaging) and ex vivo tissue distribution. Single-agent AP treatment and combinations with MTX were well tolerated. Both prophylactic and therapeutic AP markedly reduced synovial macrophage infiltration in arthritic knees (ED1: 3.5- to 4-fold; ED2: 3.5- to 6-fold), comparable with MTX treatment. AP-MTX combinations slightly improved on single agent effects. PET monitoring and ex vivo tissue distribution studies corroborated the impact of AP, MTX, and AP-MTX on reducing synovial macrophage infiltration. Beyond localized articular effects, AP also revealed systemic anti-inflammatory effects by a 2-fold reduction of ED1, ED2, and FRß+ macrophages in liver and spleen of arthritic rats. Collectively, single-agent AP and AP combined with MTX elicited local and systemic anti-arthritic activity in arthritic rats.

Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [18F]Fluoro-PEG-Folate.

Background: In rheumatoid arthritis, articular inflammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defined. Here, we examined the feasibility of PET imaging with the macrophage tracer [18F]fluoro-PEG-folate, targeting folate receptor ß (FRß), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment. Methods: [18F]Fluoro-PEG-folate PET scans (60 min) were acquired in saline- and MTX-treated (1 mg/kg, 4x) arthritic rats, followed by tissue resection and radiotracer distribution analysis. Liver and spleen tissues were stained for ED1/ED2-macrophage markers and FRß expression. Results: [18F]Fluoro-PEG-folate PET and ex vivo tissue distribution studies revealed a significant (p < 0.01) 2-fold lower tracer uptake in both liver and spleen of MTX-treated arthritic rats. Consistently, ED1- and ED2-positive macrophages were significantly (p < 0.01) decreased in liver (4-fold) and spleen (3-fold) of MTX-treated compared with saline-treated rats. Additionally, FRß-positive macrophages were also significantly reduced in liver (5-fold, p < 0.005) and spleen (3-fold, p < 0.01) of MTX- versus saline-treated rats. Conclusions: MTX treatment reduced activated macrophages in liver and spleen, as markers for systemic inflammation in these organs. Macrophage PET imaging with [18F]fluoro-PEG-folate holds promise for detection of systemic inflammation in RA as well as therapy (MTX) response monitoring.

Effects of Variety and Postharvest Handling Practices on Microbial Population at Different Stages of the Value Chain of Fresh Tomato (Solanum lycopersicum) in Western Terai of Nepal.

Background. Fresh vegetables such as tomato should have low microbial population for safe consumption and long storage life. The aerobic bacterial count (ABC) and coliform bacterial count (CBC), yeast, and mold population are the most widely used microbial indicators in fresh vegetables which should be lower than 4 log CFU g-1 for safe consumption. The stages of the supply chain, postharvest handling methods, and crop varieties had significant effects on microbial population. ABC, CBC, yeast, and mold population were significantly highest (P < 0.05) at retail market (5.59, 4.38, 2.60, and 3.14 log CFU g-1, resp.), followed by wholesale market (4.72, 4.71, 2.43, and 2.44 log CFU g-1, resp.), and were least at farm gate (3.89, 3.63, 2.38, and 2.03 log CFU g-1, resp.). Improved postharvest practices (washing in clean water and grading and packaging in clean plastic crate) helped to reduce ABC, CBC, and mold population by 2.51, 32.70, and 29.86 percentage as compared to the conventional method (no washing and no grading and packaging in mud plastered bamboo baskets). Among varieties, Pusa ruby had the lowest microbial load of 2.58, 4.53, 0.96, and 1.77 log CFU g-1 for ABC, CBC, yeast, and mold count, respectively. Significantly negative correlation (P < 0.05) was observed between fruit pH & ABC and pH & mold count. Although the microbial quality of fresh tomato is safe in the local market of western Terai of Nepal both in conventional and in improved practices however still it is essential to follow improved postharvest handling practices in production and marketing of newly introduced tomato cultivars (high-pH cultivars) for ensuring the safe availability of fresh tomato in the market.

Engineering double-stranded RNA binding activity into the Drosha double-stranded RNA binding domain results in a loss of microRNA processing function.

Canonical processing of miRNA begins in the nucleus with the Microprocessor complex, which is minimally composed of the RNase III enzyme Drosha and two copies of its cofactor protein DGCR8. In structural analogy to most RNase III enzymes, Drosha possesses a modular domain with the double-stranded RNA binding domain (dsRBD) fold. Unlike the dsRBDs found in most members of the RNase III family, the Drosha-dsRBD does not display double-stranded RNA binding activity; perhaps related to this, the Drosha-dsRBD amino acid sequence does not conform well to the canonical patterns expected for a dsRBD. In this article, we investigate the impact on miRNA processing of engineering double-stranded RNA binding activity into Drosha's non-canonical dsRBD. Our findings corroborate previous studies that have demonstrated the Drosha-dsRBD is necessary for miRNA processing and suggest that the amino acid composition in the second α-helix of the domain is critical to support its evolved function.

A fluorescence-electrochemical study of carbon nanodots (CNDs) in bio- and photoelectronic applications and energy gap investigation.

Carbon nanodots (CNDs) have attracted great attention due to their superior solubility, biocompatibility, tunable photoluminescence, and opto-electronic properties. This work describes a new fluorescence-based spectroelectrochemistry approach to simultaneously study the photoluminescence and wavelength dependent photocurrent of microwave synthesized CNDs. The fluorescence of CNDs shows selective quenching upon a reversible redox couple, ferricyanide/ferrocyanide, reaction during cyclic voltammetry. The CND modified gold slide electrode demonstrates wavelength dependent photocurrent generation during the fluorescence-electrochemical study, suggesting the potential application of CNDs in photoelectronics. UV-Vis absorption and electrochemistry are used to quantify the energy gap of the CNDs, and then to calibrate a Hückel model for CNDs' electronic energy levels. The Hückel (or tight binding) model treatment of an individual CND as a molecule combines the conjugated π states (C[double bond, length as m-dash]C) with the functional groups (C[double bond, length as m-dash]O, C-O, and COOH) associated with the surface electronic states. This experimental and theoretical investigation of CNDs provides a new perspective on the optoelectronic properties of CNDs and should aid in their development for practical use in biomedicine, chemical sensing, and photoelectric devices.

In-vivo monitoring of anti-folate therapy in arthritic rats using [18F]fluoro-PEG-folate and positron emission tomography.

BACKGROUND: Folate receptor ß (FRß) is involved in facilitating cellular uptake of folates and anti-folates (such as methotrexate (MTX)). In rheumatoid arthritis, FRß is expressed on synovial macrophages and recently has been explored as a biomarker for imaging in arthritic rats using the folate-based positron emission tomography (PET) tracer [18F]fluoro-PEG-folate. The purpose of this study was to examine whether this folate tracer can also be used to monitor therapeutic efficacy of MTX in arthritic rats. METHODS: Arthritic rats received either no treatment or MTX therapy (1 mg/kg, either 2× or 4×). Healthy rats did not receive any arthritic induction or therapy. [18F]fluoro-PEG-folate PET-CT scans (60 min) were performed before and after MTX therapy. Following PET, the ex-vivo tissue distribution of radioactivity was determined in excised knees and multiple tissues. Synovial macrophage infiltration in knee sections was quantified by immunohistochemistry using ED1 and ED2 antibodies. RESULTS: PET scans clearly visualized increased uptake of [18F]fluoro-PEG-folate in arthritic knees compared with contralateral knees. Significantly lower standard uptake values (1.5-fold, p < 0.01) were observed in arthritic knees of both MTX-treated groups after therapy, approximating the levels seen in healthy rats. Consistently, ex-vivo tissue distribution demonstrated a 2-4-fold lower tracer uptake in the arthritic knee of 2× and 4× MTX-treated rats, respectively, compared with control rats. These results were corroborated with significantly reduced (2-4-fold, p < 0.01) ED1-positive and ED2-positive synovial macrophages in arthritic knees of the MTX-treated rats compared with those of the control rats. CONCLUSION: This study in arthritic rats underscores the potential and usefulness of [18F]fluoro-PEG-folate PET as a therapeutic monitoring tool of MTX therapy and potentially other anti-folate treatment of arthritis.