A Review on Potential Footprints of Ferulic Acid for Treatment of Neurological Disorders.

Ferulic acid is being screened in preclinical settings to combat various neurological disorders. It is a naturally occurring dietary flavonoid commonly found in grains, fruits, and vegetables such as rice, wheat, oats, tomatoes, sweet corn etc., which exhibits protective effects against a number of neurological diseases such as epilepsy, depression, ischemia-reperfusion injury, Alzheimer's disease, and Parkinson's disease. Ferulic acid prevents and treats different neurological diseases pertaining to its potent anti-oxidative and anti-inflammatory effects, beside modulating unique neuro-signaling pathways. It stays in the bloodstream for longer periods than other dietary polyphenols and antioxidants and easily crosses blood brain barrier. The use of novel drug delivery systems such as solid-lipid nanoparticles (SLNs) or its salt forms (sodium ferulate, ethyl ferulate, and isopentyl ferulate) further enhance its bioavailability and cerebral penetration. Based on reported studies, ferulic acid appears to be a promising molecule for treatment of neurological disorders; however, more preclinical (in vitro and in vivo) mechanism-based studies should be planned and conceived followed by its testing in clinical settings.

S1P Signaling Genes as Prominent Drivers of BCR-ABL1-Independent Imatinib Resistance and Six Herbal Compounds as Potential Drugs for Chronic Myeloid Leukemia.

Imatinib (IM), a breakthrough in chronic myeloid leukemia (CML) treatment, is accompanied by discontinuation challenges owing to drug intolerance. Although BCR-ABL1 mutation is a key cause of CML resistance, understanding mechanisms independent of BCR-ABL1 is also important. This study investigated the sphingosine-1-phosphate (S1P) signaling-associated genes (SphK1 and S1PRs) and their role in BCR-ABL1-independent resistant CML, an area currently lacking investigation. Through comprehensive transcriptomic analysis of IM-sensitive and IM-resistant CML groups, we identified the differentially expressed genes and found a notable upregulation of SphK1, S1PR2, and S1PR5 in IM-resistant CML. Functional annotation revealed their roles in critical cellular processes such as proliferation and GPCR activity. Their network analysis uncovered significant clusters, emphasizing the interconnectedness of the S1P signaling genes. Further, we identified interactors such as BIRC3, TRAF6, and SRC genes, with potential implications for IM resistance. Additionally, receiver operator characteristic curve analysis suggested these genes' potential as biomarkers for predicting IM resistance. Network pharmacology analysis identified six herbal compounds-ampelopsin, ellagic acid, colchicine, epigallocatechin-3-gallate, cucurbitacin B, and evodin-as potential drug candidates targeting the S1P signaling genes. In summary, this study contributes to efforts to better understand the molecular mechanisms underlying BCR-ABL1-independent CML resistance. Moreover, the S1P signaling genes are promising therapeutic targets and plausible new innovation avenues to combat IM resistance in cancer clinical care in the future.

Impact of Dapagliflozin Adjunctive Therapy on the Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease Stages 2-5: A systematic review and meta-analysis.

This meta-analysis investigated efficacy of dapagliflozin as adjunctive therapy for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) stages 2-5. A systematic search was conducted of selected databases for randomised controlled trials that reported the mean change in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) from baseline. Out of 1,682 identified studies, 9 trials comprising 13,057 patients were included. A pooled estimate of 5 studies indicated that dapagliflozin did not affect eGFR; however, in 2 studies, it significantly reduced chronic eGFR decline compared to placebo (mean difference [MD] ± 2.74; 95% confidence interval [CI]: 1.55, 3.92; P <0.00001). Additionally, a pooled estimate of 4 studies showed that dapagliflozin significantly reduced UACR (MD -23.99%; 95% CI: -34.82--13.15; P <0.0001; I2 = 0%). Therefore, long-term use of dapagliflozin significantly attenuates eGFR decline and reduces albuminuria in patients with T2DM and CKD.

Is Sphingosine Kinase 1 Associated with Hematological Malignancy? A Systematic Review and Meta-Analysis.

BACKGROUND: Sphingosine kinase 1 (SphK1) is a lipid enzyme whose role in the etiology of cancer has been well explored. Here, a systematic review and meta-analysis were conducted to evaluate the association of SphK1 expression with hematological malignancy. MATERIALS AND METHODS: Relevant studies were identified through electronic databases (PubMed, Scopus, Embase, and OVID) and evaluated based on predefined inclusion and exclusion criteria. Quality assessment using the Newcastle-Ottawa Scale (NOS) was conducted, and pooled odds ratio (OR) was calculated to assess the association between SphK1 expression and hematological malignancy. RESULTS: Nine studies meeting the inclusion criteria were included in the systematic review. These studies utilized various techniques to assess SphK1 expression in hematological malignancies. The quality assessment reported that the included studies were of moderate quality. Meta-analysis of eligible studies revealed a positive association between SphK1 expression and hematological malignancies at the protein level (OR = 52.37, 95% CI = 10.10 to 271.47, and P = 0.00001). The funnel plot indicated no publication bias among the included studies. However, the certainty of the evidence was low according to the GRADE assessment. CONCLUSION: Our study's findings support the link between SphK1 expression and hematological malignancies. SphK1 gene dysregulation may contribute to various malignancies, suggesting it could be a therapeutic target to improve patient outcomes. Further research is needed to understand SphK1's mechanistic role in hematological malignancies and its therapeutic potential.

Hypothalamus-pituitary-adrenal axis (HPA axis) suppression with inappropriate use of steroids in recalcitrant dermatophytosis - A cross-sectional study.

Background: Improper use of over-the-counter (OTC) steroid medication has been linked to recalcitrant dermatophytosis. There is proven evidence of HPA axis suppression by the use of long-term oral steroids. This study aims to determine the prevalence and pattern of inappropriate OTC steroid use and its effects on the hypothalamus-pituitary-adrenal (HPA) axis in adults with recalcitrant dermatophytosis. Materials and Methods: This cross-sectional study of 2 months was conducted in a hospital setting and included patients of recalcitrant dermatophytosis with a history of OTC steroid use. Clinico-demographic details and basal serum cortisol levels were recorded in all and analyzed. Result: Of a total of 103 patients, 59.22% (n = 61/103) were males, and the mean duration of steroid abuse was 17.78 months. About 48.54% (n = 50/103), 3.88% (n = 4/103), and 47.57% (n = 49/103) patients reported the use of topical steroids, oral steroids, and both oral and topical steroids, respectively. Among all the topical steroid users (n = 99), clobetasol propionate 48.48% (n = 48/99), while among oral steroid users (n = 53), prednisolone 45.28% (n = 24/53) were the most commonly used agents, respectively. The morning serum cortisol levels (8-9 AM) were found to be decreased in 42.7% (n = 44/103), with a mean value of 44.28 ± 17.34 µg/dL. Conclusion: Improper OTC steroid use in recalcitrant dermatophytosis leads to HPA axis suppression. This highlights the need for intervention from apex health officials.

The Cost-Effectiveness of and Adherence to Disease-Modifying Antirheumatic Drug (DMARD) Therapy in Rheumatoid Arthritis Patients in a Tertiary Care Teaching Hospital in Uttarakhand, India.

Objective This study was conducted with the aim of evaluating the cost-effectiveness of and adherence to treatment in patients on disease-modifying antirheumatic drug (DMARD) therapy for rheumatoid arthritis (RA) in a tertiary care teaching hospital in Uttarakhand, India. Methodology This prospective observational study was conducted on 150 rheumatoid arthritis patients presenting to the Rheumatology Outpatient Department (OPD) receiving DMARD therapy (approval number AIIMS/IEC/18/160). The patients were followed up for an average of 10.7 weeks and received drugs in four regimens with methotrexate (MTX) (Regimen 1) having the least contribution with a mean of 46.05 Rs, methotrexate + hydroxychloroquine (MTX + HCQ) (Regimen 2) with 174.15 Rs, methotrexate + hydroxychloroquine + leflunomide (MTX + HCQ + Lef) (Regimen 3) with Rs 371.70, and methotrexate + hydroxychloroquine + leflunomide + biological DMARD adalimumab (MTX + HCQ + Lef + bDMARD adalimumab) (Regimen 4) with 17,349.4 Rs. The cost of drug therapy was assessed by calculating the cost of therapy per month for each patient, and adherence was assessed using the Morisky-Green-Levine Scale (MGLS) at the follow-up visit. Results The overall mean cost of DMARD treatment was 205.81 Rs. The overall DMARD therapy cost-effectiveness was Rs 878.14 for a unit change of Disease Activity Score (DAS28). The most cost-effective treatment came out to be Regimen 1 with the least cost of 290.9 Rs for a unit change of DAS28, and the least cost-effective was Regimen 4 with 65,661.8 Rs for a unit change of DAS28. At follow-up, among all subjects of the study, 49 (32.7%) subjects showed high adherence, 71 (47.3%) subjects showed medium adherence, and 30 (20%) subjects showed low adherence. Accordingly, the maximum number of participants fell in the category of medium adherence, i.e., 71 (47.4%). Conclusion Our study concluded that the cost burden varied according to the number of DMARDs being given to the patient. The double-drug therapy of methotrexate + hydroxychloroquine had a maximum "high adherence." On a whole, the majority of patients had "medium adherence" to therapy.

Association of depression with disease duration, quality of life and adherence in Parkinson's disease: A cross sectional study.

Background: Parkinson's disease (PD) is a progressive motor disorder often accompanied by non-motor symptoms such as depression. Objectives: The objective was to estimate the prevalence of depression in PD patients, and assess its association with disease duration, quality of life and adherence to treatment. Materials and Methods: This cross-sectional study was conducted in a tertiary care centre for patients diagnosed with PD. Depression was diagnosed using Hamilton Depression Rating Scale. The Chi-square test was used to assess the difference in proportions of depression in various types and severity of PD. Depression was also correlated with disease duration, quality of life (QOL) and adherence to treatment using the Pearson correlation test. A P value of <0.05 was considered statistically significant. Results: Among 51 patients, 20 (39.22%) patients were found to have depression. The mean duration of disease in depressed patients was significantly longer compared to that in non-depressed patients (7.99 ± 4.53 vs. 3.62 ± 2.23, P < 0.001), respectively. The non-depressed patients were better adherent to treatment (1.71 ± 1.5 vs. 0.56 ± 0.91). The quality of life of patients was significantly low for depressed patients (21.90 ± 6.91 vs. 13.16 ± 6.93, P < 0.001). Depression in Parkinson's patients was positively correlated with the duration of the disease (P-value <0.001); disease staging (P-value <0.001). Quality of life (QOL) had a strong correlation with depression (P-value <0.001) and Hoehn and Yahr (HY) staging (P-value <0.05). Conclusion: Depression was found in 39.22% of PD patients and was more significantly associated with disease duration, non-adherence to treatment and decreased quality of life.

Prescribing pattern of anti-diabetic drugs and adherence to the American Diabetes Association's (ADA) 2021 treatment guidelines among patients of type 2 diabetes mellitus: A cross-sectional study.

Background: Glycemic control is the major therapeutic objective in diabetes. Poor glycemic control in diabetes mellitus can be prevented by using rational use of anti-diabetic medication, which needs to be evaluated for effectiveness by prescription pattern studies. The objective of this study was to assess the prescribing pattern and adherence to the American Diabetic Association's (ADA) treatment guidelines in type 2 diabetes mellitus patients in a tertiary care teaching hospital in Uttarakhand, India. Methodology: This cross-sectional study was conducted on 206 type 2 diabetic patients who were prescribed anti-diabetic therapy. Patient's demographic details and drugs prescribed, with their dosage, were recorded to study the prescription pattern. Results: Oral anti-diabetic drugs were most commonly prescribed in 149 (72.33%) type 2 diabetic mellitus patients. Five of these patients (3.35%) were on metformin monotherapy, whereas majority of patients (81, 54.36%) were on a fixed dose combination of Glimepiride (SU) + Metformin (MET). Forty-five patients (30.20%) were on MET + Dipeptidyl peptidase 4 inhibitors (DPP4I) combination; 5 (3.35%) were on MET + SU + alpha-glucosidase inhibitors (AGI) combination; 7 (4.69%) were on MET + SU + Pioglitazone (PIO) (Thiazolidinediones) combination; 6 (4.02%) were on sodium/glucose cotransporter-2 inhibitors (SGLT2I) and 57 (27.66%) were on insulin therapy. Out of 206 patients, the prescriptions of 185 patients (89.8%) were adherent and of 21 patients (10.19%) were not adhering to ADA 2021 treatment guidelines. Conclusion: Oral anti-diabetic agents predominate the prescribing pattern practices for type 2 DM but there was a shift in trend towards the use of fixed-dose combinations (FDC) in the management of type 2 DM, and majority of prescriptions were adherent to ADA treatment guidelines.

Efficacy of Ferulic Acid in an Animal Model of Drug-Resistant Epilepsy: Beneficial or Not?

Background Lamotrigine (LTG) and subconvulsive doses of pentylenetetrazol (PTZ) as a model mimic drug-resistant epilepsy (DRE), which is a serious unmet medical condition. Previous evidence suggests an imperative role of neuroinflammation in the development of DRE. Various preclinical models of brain injury have reported potent anti-inflammatory and antioxidant properties of ferulic acid (FA). Therefore, its efficacy against intractable epilepsy is worthwhile to study. Materials and methods The present study evaluated the efficacy of FA in LTG and PTZ-induced refractory seizures in mice. On every alternate day for 38 days, LTG (5mg/kg) was injected before PTZ (30-40mg/kg) to establish a murine model of DRE. Animals were treated with two doses of FA (40, 80 mg/kg). All the animals were assessed for seizure score and the latency of seizures every alternate day till the end of the study. Histopathological score and the levels of pro-inflammatory mediators, interleukin-1ßeta (IL-Iß), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) were quantified in the brain tissue of these mice.  Results Ferulic acid (FA) neither decreases the LTG and PTZ-induced refractory seizures score nor increases the latency to develop seizures. In addition, the injury to hippocampal neurons and the levels of pro-inflammatory cytokines were comparable with two doses of FA in treated mice. Conclusion In the present study, single-dose FA treatment does not show any beneficial effect against the LTG/PTZ model of DRE. Therefore, its single-dose administration might not be beneficial against the DRE model.

Dimethyl Fumarate Ameliorates Paclitaxel-Induced Neuropathic Pain in Rats.

Background Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is nonresponsive to the currently available analgesics. Previous studies have shown the role of oxidative stress and central sensitization in the development of peripheral neuropathy. Dimethyl fumarate (DMF) acts as a nuclear factor erythroid-2-related factor 2 (Nrf2) activator with neuroprotective benefits and is approved for use in multiple sclerosis. Materials and methods In the current research, we evaluated the efficacy of DMF on paclitaxel-induced peripheral neuropathy in rats. Every alternate day for one week, paclitaxel 2 mg/kg dose was injected to establish a rat model of PIPN. Animals were treated with 25 mg/kg and 50 mg/kg of DMF. All the animals were assessed for thermal hyperalgesia, cold allodynia, and mechanical allodynia once a week. The gene expression of Nrf2 and the levels of pro-inflammatory mediators (interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and IL-1ß) were quantified in the sciatic nerves of these rats. The levels of p38 mitogen-activated protein kinase (MAPK) and brain-derived neurotrophic factor (BDNF) were quantified in the dorsal horn of the spinal cord. Results DMF significantly attenuated paclitaxel-induced thermal hyperalgesia and cold/mechanical allodynia. A significant decrease in the levels of pro-inflammatory cytokines with the levels of p38 MAPK and BDNF was observed in the DMF-treated animals. DMF treatment significantly upregulated the gene expression of Nrf2 in the sciatic nerve. Conclusion These findings suggest that DMF prevented the development of PIPN in rats through the activation of Nrf2 and the inhibition of p38 MAPK and BDNF.

Evaluation of prescription practices in rheumatoid arthritis at the rheumatology clinic in a tertiary care teaching hospital in Uttarakhand: A cross-sectional study.

OBJECTIVE: This study was aimed to analyze the prescription pattern of disease modifying anti-rheumatic drug (DMARD) therapy in patients with rheumatoid arthritis (RA) in a tertiary care teaching hospital in Uttarakhand, India. METHODOLOGY: This cross-sectional study was conducted in 150 RA patients who were given DMARD therapy. Patient's demographic details, drugs prescribed with their dosage and administration routes and the usage of complementary and alternative medicine (CAM) therapy were recorded to study the prescription pattern. RESULTS: Overall, 4 DMARDs were prescribed in all the studied patients: Methotrexate (n = 150), hydroxychloroquine (n = 35), leflunomide (n = 5), and adalimumab (n = 1). Single DMARD therapy with methotrexate was prescribed to 110 (73.3%) followed by double therapy with methotrexate + hydroxychloroquine in 35 (23.3%), triple therapy (methotrexate + hydroxychloroquine + leflunomide) in 4 (2.7%) and triple therapy with biological DMARD (methotrexate + hydroxychloroquine + leflunomide + adalimumab) in 1 (0.7%) patient. Adjuvant therapy drugs included: Prednisolone (n = 150), folic acid (n = 150), naproxen (n = 150), calcium (n = 150), vitamin D (n = 150) and indomethacin (n = 40). Of the total, 61.4% patients also took complimentary alternative medicine (CAM) therapy. CONCLUSION: Our study concludes that the most commonly prescribed DMARDs in our setting, to patients of RA, in descending order of frequency were methotrexate, followed by hydroxychloroquine, leflunomide and lastly adalimumab. A total of five adjuvant medications were commonly prescribed to all patients. There was a high prevalence of self-medicated CAM therapy in the majority of these patients.

A prospective, follow up study to assess guidelines compliance in uncomplicated urinary tract infection.

BACKGROUND AND AIMS: The study was undertaken to assess the empirical antibiotic prescription in uncomplicated urinary tract infection (UTI) cases and compare them with the Indian council of medical research (ICMR) 2017 guidelines on antimicrobial use. The objective of this study was to study the compliance of prescriptions for uncomplicated UTI with respect to the guidelines recommended by ICMR and assess the success rates in terms of mean days taken to achieve symptomatic relief. METHODOLOGY: This study was conducted on patients (of age >16 years) presenting to the Urology, Medicine and Gynecology OPD with complaints of uncomplicated UTI over two months. Descriptive statistics were used to assess the results. RESULTS: A total of 115 UTI patients were enrolled and followed up for symptomatic relief. 67 (58.26%) patients were prescribed antibiotics, the preferred ones were levofloxacin 500 mg O.D. in 24 (35.82%), nitrofurantoin 100 mg B.D. in 21 (31.34%) and levofloxacin 750 mg O.D. in 6 (8.95%) patients for a mean duration of 7.83 ± 2.37, 7.52 ± 2.68 and 4.33 ± 1.03 days respectively. Symptomatic relief was seen in 6 (25%), 15 (71.42%) and 4 (66.67%) cases within 5 ± 0.63 days, 4.2 ± 2.11 days and 4.5 ± 1 days, respectively. DISCUSSION: 23 (34.32%) prescriptions based on choice of empirical antibiotic and 17 (25.37%) prescriptions based on both choice of antibiotic and duration of therapy were found to be compliant with the (ICMR) -2017 guidelines. Results show decreased efficacy of co-trimoxazole and ciprofloxacin as empirical therapy for acute uncomplicated UTI.

Rosai Dorfman syndrome with extranodal manifestation.

Rosai Dorfman Syndrome (RDS) is a benign condition and a rare cause of cervical lymphadenopathy. It usually occurs in the first decade of life and manifest as massive enlargement of cervical lymph nodes. The disease has a benign course and involvement of the nasal cavity as an extranodal site is exceptional. A 22-year-old male presented as progressive massive bilateral cervical lymphadenopathy accompanied with nasal obstruction and occasional episodes of epistaxis. A FNAC from cervical lymph node and biopsy from nasal mass was compatible with RDS.

Pattern of Adverse Drug Reactions to Anticancer Drugs: A Quantitative and Qualitative Analysis.

INTRODUCTION: Anticancer drugs contribute significantly to the global burden of adverse drug reactions (ADRs). Any attempt to quantify their magnitude and provide upgraded knowledge would help oncologists in writing safer prescriptions. AIM: This observational follow-up study was conducted on newly diagnosed cancer patients receiving anticancer therapy with an aim to determine the frequency, severity, causality, predictability, and preventability of ADRs. SUBJECTS AND METHODS: The patients were followed up for 6 months for the appearance of adverse events. Data were analyzed using IBM SPSS Statistics for Windows, Version 22.0. (Armonk, NY) and presented in the form of descriptive statistics. RESULTS: Each patient was prescribed approximately 6.85 ± 1.51 (mean ± standard error) drugs on average. All the patients (100%) receiving anticancer chemotherapy had ADRs. Alopecia, nausea and vomiting, burning tingling, and numbness were the most frequently encountered ADRs. The incidence of alopecia (P < 0.0004), nausea (P < 0.03), and oral ulceration (P < 0.02) was higher in females. Maximum reactions were of Grade 2 (69.53%). Most of the reactions (75.80%) appeared within 10 days of receiving the first cycle. 99.58% reactions were not serious. According to the WHO - The Uppsala Monitoring Centre criteria, 99.47% ADRs fell in possible category. According to the Naranjo's algorithm, 100% ADRs fell in probable category. About 94.80% reactions were found to be predictable. About 56.47% reactions were probably preventable, and 43.53% reactions were not preventable. CONCLUSION: Multiple ADRs were seen in newly diagnosed cancer patients. Most of them were predictable, of mild-to-moderate severity, nonserious, and preventable. A majority of the ADRs recovered over time.

Multiplexed magnetic nanoparticle-antibody conjugates (MNPs-ABS) based prognostic detection of ovarian cancer biomarkers, CA-125, ß-2M and ApoA1 using fluorescence spectroscopy with comparison of surface plasmon resonance (SPR) analysis.

A multiplexed MNPs-Abs based fluorescence spectroscopic system in analysis of serum biomarkers; CA-125, ß2-M and ApoA1 for the early detection of ovarian cancer was first time proposed. The lowest detection limits measured in multiplexed setup were 0.26 U/mL, 0.55 ng/mL and 7.7 ng/mL respectively for CA-125, ß2-M and ApoA1. A comparative real sample analysis of healthy normal (Control), benign and ovarian cancer patients with SPR has also been done to validate the process. Moreover CA-125 detection only confirms 50-60% of early stage disease. This multiplexed system achieved sensitivity and specificity up to 94% and 98% respectively to distinguish early stage ovarian cancer patients from healthy individuals.

Effect of educational intervention on adverse drug reporting by physicians: a cross-sectional study.

In India, the pharmacovigilance program is still in its infancy. National Pharmacovigilance Program of India was started for facilitating the pharmacovigilance activities. The ADR reporting rate is still below satisfactory in India. This cross-sectional questionnaire based study was carried out in a tertiary care teaching hospital in Uttarakhand, which is a peripheral ADR monitoring centre to assess the level of knowledge, attitude, and the practices of pharmacovigilance among the doctors and to compare it with the group of doctors attending educational CME for improving awareness of pharmacovigilance. The most important revelation of this study was that although adequate knowledge and the right attitude about adverse drug reaction reporting were instigated in the doctors after the educational intervention, the practice was still neglectful in both groups, emphasizing the need to design the strategies to develop adverse drug reaction reporting culture.