Glioblastoma (GBM) conventional treatment is not curative, and it is associated with severe toxicity. Thus, natural compounds with anti-cancer properties and lower systemic toxicity, such as gallic acid (GA), have been explored as alternatives. However, GA\'s therapeutic effects are limited due to its rapid metabolism, low bioavailability, and low permeability across the blood-brain barrier (BBB). This work aimed to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with folic acid (FA), as its receptor is overexpressed in BBB and GBM cells, for GA delivery to enhance its therapeutic efficacy. The preparation of NPs was optimized by a central composite design (CCD). The obtained NPs showed physicochemical features suitable for drug internalization in BBB and tumor cells (sizes below 200 nm, monodispersity, and negative surface charge) and the ability to maintain a slow and sustained release for 40 days. In vitro studies using a human GBM cell line (U215) revealed the NPs\' ability to accumulate in the target cells, further promoting GA antiproliferative activity by inducing the production of intracellular reactive oxygen species (ROS). Furthermore, GA encapsulation in the developed nanosystems conferred higher protection to healthy cells.

Fanconi syndrome (FS) is a complex disorder characterized by a reabsorption defect in the proximal renal tubule (PT), leading to urinary loss of molecules such as glucose, phosphate, calcium, amino acids, bicarbonate, potassium, and low-molecular-weight proteins. Its etiology can be genetic or acquired, with drug toxicity being a significant cause of the acquired forms. The heterogeneous manifestations of FS, whether in its partial or complete form, can pose challenges in the emergency department; nevertheless, it should be considered in certain patients, as understanding its cause is crucial for initiating effective treatment. We present the case of a 59-year-old female patient with FS who was treated with lenalidomide in the context of stage III IgG kappa multiple myeloma according to the Salmon Durie classification. We highlight the recurrent nature of this syndrome in this patient.

Antineoplastic agents are often associated with a wide range of side effects, caused by either direct toxicity or indirect through their metabolism. Ifosfamide is a cytotoxic, antineoplastic medication that is known to cause a direct tubular injury with an associated normal anion gap metabolic acidosis due to type 1 or type 2 renal tubular acidosis (RTA). The manifestations and approach to its diagnosis have been well established. However, we present a case in which a patient presented with acute symptomatic hypokalemia in the setting of ongoing ifosfamide use for metastatic osteosarcoma but without the typical laboratory findings. The clinical- and laboratory-driven diagnosis of suspected type 3 renal tubular acidosis involving proximal and distal segments is suggested by this case report.

Multiple therapies have been studied to ameliorate the neuroinhibitory cues present after traumatic injury to the central nervous system. Two previous in vitro studies have demonstrated the efficacy of the FDA-approved cardiovascular therapeutic, protamine (PRM), to overcome neuroinhibitory cues presented by chondroitin sulfates; however, the effect of a wide range of PRM concentrations on neuronal and glial cells has not been evaluated. In this study, we investigate the therapeutic efficacy of PRM with primary cortical neurons, hippocampal neurons, mixed glial cultures, and astrocyte cultures. We show the threshold for PRM toxicity to be at or above 10 μg/ml depending on the cell population, that 10 μg/ml PRM enables neurons to overcome the inhibitory cues presented by chondroitin sulfate type A, and that soluble PRM allows neurons to more effectively overcome inhibition compared to a PRM coating. We also assessed changes in gene expression of reactive astrocytes with soluble PRM and determined that PRM does not increase their neurotoxic phenotype and that PRM may reduce brevican production and serpin transcription in cortical and spinal cord astrocytes. This is the first study to thoroughly assess the toxicity threshold of PRM with neural cells and study astrocyte response after acute exposure to PRM in vitro.

In developing countries like India, Linezolid is widely used for the treatment of Multi drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Long-term administration of Linezolid is reported to cause toxic optic neuropathy causing bilateral, progressive visual loss in patients. We report case details of three patients on anti-tubercular therapy presented to us with sudden, progressive, painless blurring of vision of both eyes the cause of which was confirmed to be toxic optic neuropathy due to linezolid. Subsequently, cessation of the drug resulted in complete visual recovery in two patients whereas one patient had minimal visual improvement due to secondary optic atrophy. Clinicians and health care workers need to be aware of sight threatening complications of Linezolid.

BACKGROUND: Pharmacovigilance entails monitoring of patients for timely detection of ADR and reporting them so that more information about drug safety can be obtained. This may help in the future for dose modification or alteration of regimen. In NTEP, ADSm (Active Drug Safety monitoring) is part of pharmacovigilance. In this study we shall be studying ADRs to Anti TB drugs in DRTB.
METHODS: This study is observational, retrospective and record based, of patients admitted from 2021 to 2023 in the DOTS ward of Respiratory Medicine Department of a tertiary care hospital in Goa. Data such as age, sex, regimen, date of AKT initiation and adverse effects documented has been noted and compiled.
RESULTS: ADRs have been tabulated in the form of tables. Statistical analysis is done to find out the commonest ADR, time when they are likely to occur, which age and gender are most likely affected and if there are any other associated risk factors for ADRs.
CONCLUSIONS: This study will enable in future to better monitor patients with regard to particular adverse drug reaction, patient safety and if needed to alter the regimen as early as possible.

Our knowledge of the roles of individual cytochrome P450 (P450, CYP) enzymes in drug metabolism has developed considerably in the past 30 years, and this base has been of considerable use in avoiding serious issues with drug interactions and issues due to variations. Some newer approaches are being considered for \"phenotyping\" of metabolism reactions with new drug candidates. Endogenous biomarkers are being used for non-invasive estimation of levels of individual P450 enzymes. There is also the matter of some remaining \"orphan\" P450s, which have yet to be assigned reactions. Practical problems that continue in drug development include predicting drug-drug interactions, predicting the effects of polymorphic and other P450 variations, and evaluating inter-species differences in drug metabolism, particularly in the context of \"metabolism in safety testing\" (MIST) regulatory issues (\"disproportionate (human) metabolites\"). Significance Statement Cytochrome P450 enzymes are the major catalysts involved in drug metabolism. The characterization of their individual roles has major implications in drug development and clinical practice.

Introduction: Colistin (CMS) is used for the curation of infections caused by multidrug-resistant bacteria. CMS is constrained by toxicity, particularly in kidney and neuronal cells. The recommended human doses are 2.5-5 mg/kg/day, and the toxicity is linked to higher doses. So far, the in vivo toxicity studies have used doses even 10-fold higher than human doses. It is essential to investigate the impact of metabolic response of doses, that are comparable to human doses, to identify biomarkers of latent toxicity. The innovation of the current study is the in vivo stimulation of CMS\'s impact using a range of CMS doses that have never been investigated before, i.e., 1 and 1.5 mg/kg. The 1 and 1.5 mg/kg, administered in mice, correspond to the therapeutic and toxic human doses, based on previous expertise of our team, regarding the human exposure. The study mainly focused on the biochemical impact of CMS on the metabolome, and on the alterations provoked by 50%-fold of dose increase. The main objectives were i) the comprehension of the biochemical changes resulting after CMS administration and ii) from its dose increase; and iii) the determination of dose-related metabolites that could be considered as toxicity monitoring biomarkers. Methods: The in vivo experiment employed two doses of CMS versus a control group treated with normal saline, and samples of plasma, kidney, and liver were analysed with a UPLC-MS-based metabolomics protocol. Both univariate and multivariate statistical approaches (PCA, OPLS-DA, PLS regression, ROC) and pathway analysis were combined for the data interpretation. Results: The results pointed out six dose-responding metabolites (PAA, DA4S, 2,8-DHA, etc.), dysregulation of renal dopamine, and extended perturbations in renal purine metabolism. Also, the study determined altered levels of liver suberylglycine, a metabolite linked to hepatic steatosis. One of the most intriguing findings was the detection of elevated levels of renal xanthine and uric acid, that act as AChE activators, leading to the rapid degradation of acetylcholine. This evidence provides a naïve hypothesis, for the potential association between the CMS induced nephrotoxicity and CMS induced 39 neurotoxicity, that should be further investigated.

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UNASSIGNED: The purpose of this research was to investigate the characteristics, clinical manifestations, incidence, and risk factors in ethambutol-induced optic neuropathy (EON) in the Thai population.
UNASSIGNED: Patients treated with ethambutol for tuberculosis (TB) were retrospectively identified in the medical record of a tertiary hospital in Thailand from January 2012 to August 2019. Development of EON was determined through review of ophthalmology records. Comparison was made between patients with EON and those without EON to identify possible risk factors. Ophthalmic outcomes were characterized.
UNASSIGNED: Among 4,141 patients who received ethambutol for TB treatment, 1,062 had an ophthalmology encounter, and 20 (0.5% overall, 1.88% with ophthalmology encounters) developed EON. In unadjusted analysis, compared to patients without EON, those with EON had a similar daily dose, but longer duration of ethambutol treatment (P=0.02). They were older (mean 43.74 vs. 58.60 years, P=0.001), more likely to have hypertension (P=0.02) and smoke (p=0.01). There were no differences in gender, body mass index, diabetes, dyslipidemia, HIV infection or glomerular filtration rate. The peripapillary retinal nerve fiber layer, ganglion cell analysis, and vascular density as measured using retinal optical coherence tomography were impacted by EON. In adjusted logistic regression analysis, age greater than 60 (OR = 8.71, p = 0.01) and smoking (OR = 7.06, p = 0.01) were independent risk factors for EON.
UNASSIGNED: In patients treated with ethambutol, the incidence proportion of EON was 0.5% among those with ethambutol administered and 1.88% among those with ethambutol and an eye visit. Potential EON risk factors were age, hypertension, smoking, and duration of ethambutol medication. Smoking has not been associated with EON in prior studies.