Unlocking New Therapeutic Options for Vincristine-Induced Neuropathic Pain: The Impact of Preclinical Research.

Vincristine, a vinca alkaloid, is used in chemotherapy protocols for cancers such as acute leukemia, Hodgkin's disease, neuroblastoma, cervical carcinoma, lymphomas, breast cancer, and melanoma. Among the common adverse effects of vincristine is peripheral neuropathy, with most patients receiving a cumulative dose over 4 mg/m who develop varying degrees of sensory neuropathy. The onset of vincristine-induced peripheral neuropathy can greatly affect patients' quality of life, often requiring dose adjustments or the discontinuation of treatment.

Exploring the Therapeutic Potential of N-Methyl-D-Aspartate Receptor Antagonists in Neuropathic Pain Management.

Neuropathic pain (NeP) is a complex and debilitating condition that impacts millions of people globally. Although various treatment options exist, their effectiveness is often limited, and they can be accompanied by significant side effects. In recent years, there has been increasing interest in targeting the N-methyl-D-aspartate receptor (NMDAR) as a potential therapeutic approach to alleviate different types of neuropathic pain.

Evaluating the Antihyperalgesic Potential of Sildenafil-Metformin Combination and Its Impact on Biochemical Markers in Alloxan-Induced Diabetic Neuropathy in Rats.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect the sildenafil (phosphodiesterase-5 inhibitor)-metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats.

Identification, analysis and prediction of valid and false information related to vaccines from Romanian tweets.

Introduction: The online misinformation might undermine the vaccination efforts. Therefore, given the fact that no study specifically analyzed online vaccine related content written in Romanian, the main objective of the study was to detect and evaluate tweets related to vaccines and written in Romanian language.

Methods: 1,400 Romanian vaccine related tweets were manually classified in true, neutral and fake information and analyzed based on wordcloud representations, a correlation analysis between the three classes and specific tweet characteristics and the validation of several predictive machine learning algorithms.

New N-acyl Thiourea Derivatives: Synthesis, Standardized Quantification Method and In Vitro Evaluation of Potential Biological Activities.

New N-acyl thiourea derivatives with heterocyclic rings have been synthesized by first obtaining isothiocyanate, which further reacted with a heterocyclic amine, characterized by (FT-IR, NMR spectroscopy and FT-ICR) and tested for their in vitro antimicrobial, anti-biofilm and antioxidant activities to obtain a drug candidate in a lead-optimization process. From the tested compounds, those bearing benzothiazole () and 6-methylpyridine () moieties revealed anti-biofilm activity against ATCC 25922 at MBIC values of 625 µg/mL. Compound exhibited the highest antioxidant capacity (~43%) in the in vitro assay using 1,1-diphenyl-2-picrylhydrazyl (DPPH).

Effects of Venlafaxine, Risperidone and Febuxostat on Cuprizone-Induced Demyelination, Behavioral Deficits and Oxidative Stress.

Multiple sclerosis (MS) is a demyelinating, autoimmune disease that affects a large number of young adults. Novel therapies for MS are needed considering the efficiency and safety limitations of current treatments. In our study, we investigated the effects of venlafaxine (antidepressant, serotonin-norepinephrine reuptake inhibitor), risperidone (atypical antipsychotic) and febuxostat (gout medication, xanthine oxidase inhibitor) in the cuprizone mouse model of acute demyelination, hypothesizing an antagonistic effect on TRPA1 calcium channels.

In Silico and In Vitro Experimental Studies of New Dibenz[,]oxepin-11(6)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents.

In a drug-repurposing-driven approach for speeding up the development of novel antimicrobial agents, this paper presents for the first time in the scientific literature the synthesis, physico-chemical characterization, in silico analysis, antimicrobial activity against bacterial and fungal strains in planktonic and biofilm growth state, as well as the in vitro cytotoxicity of some new 6,11-dihydrodibenz[,]oxepin-11(6)one O-(arylcarbamoyl)oximes. The structures of intermediary and final substances (compounds -) were confirmed by H-NMR, C-NMR and IR spectra, as well as by elemental analysis. The in silico bioinformatic and cheminformatic studies evidenced an optimal pharmacokinetic profile for the synthesized compounds -, characterized by an average lipophilic character predicting good cell membrane permeability and intestinal absorption; low maximum tolerated dose for humans; potassium channels encoded by the hERG I and II genes as potential targets and no carcinogenic effects.

The use of structural alerts to avoid the toxicity of pharmaceuticals.

In order to identify compounds with potential toxicity problems, particular attention is paid to structural alerts, which are high chemical reactivity molecular fragments or fragments that can be transformed via bioactivation by human enzymes into fragments with high chemical reactivity. The concept has been introduced in order to reduce the likelihood that future candidate substances as pharmaceuticals will have undesirable toxic effects. A significant proportion (∼78-86%) of drugs characterized by residual toxicity contain structural alerts; there is also evidence indicating the formation of active metabolites as a causal factor for the toxicity of 62-69% of these molecules.

Therapeutic potential of certain drug combinations on paclitaxel-induced peripheral neuropathy in rats.

Background And Aims: Experimental research and clinical data support the potential combination therapy for the treatment of neuropathic pain. We aimed to investigate the analgesic effect of the following associations: gabapentin + etifoxine; tramadol + etifoxine; gabapentin + tramadol, in an experimental model of peripheral neuropathy induced by paclitaxel.

Materials And Methods: Neuropathy was induced in male Wistar rats by the daily administration of 2 mg÷kg body weight (bw) paclitaxel intraperitoneally, four days in a row.

Antifibrotic action of telmisartan in experimental carbon tetrachloride-induced liver fibrosis in Wistar rats.

Background And Aims: Liver fibrosis is the increasingly accumulation of extracellular matrix (ECM), caused by chronic liver injuries, and represents a difficult clinical challenge in the entire world. Currently, the advanced knowledge of the cellular and molecular mechanisms of liver fibrosis showed that collagen-producing cells, like activated hepatic stellate cells (HSCs), portal fibroblasts and myofibroblasts are activated by fibrogenic cytokines, such as angiotensin II, transforming growth factor-beta 1 (TGF-β1), and leptin. Because of these, we tested telmisartan, an angiotensin II (AT1) receptor blocker and a peroxisome proliferator-activated receptor-γ (PPARγ) partial agonist, for investigate its antifibrotic action, on experimental model of carbon tetrachloride-induced liver fibrosis.

Oral toxicity study of certain plant extracts containing pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds which are found in plants. Poisoning caused by these toxins is associated with acute and chronic liver damage. Tussilago farfara (coltsfoot), Petasites hybridus (common butterbur), Senecio vernalis (eastern groundsel) and Symphytum officinale (comfrey) are traditional phytotherapic species, which beside the therapeutic bioactive compounds contain PAs.

Pharmacotoxicological screening on new derivatives of beta-phenylethylamine, potential agonists of beta3-adrenergic receptors.

Background And Aims: Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity.

Influence of hyperforin on the morphology of internal organs and biochemical parameters, in experimental model in mice.

Background And Aims: Hyperforin (HY) is used to treat depression and skin irritation and has been shown a number of pharmacological activities. The literature does no cite data on changes that may occur in the body after HY intake (ethylene diammonium salt - EDS) in long-term administration. From this point of view, the present work is a key to determining the pharmacotoxicological profile of the HY-EDS, in long-term administration.

Adrenal and pituitary incidentalomas in a case of Cushing's syndrome.

Cushing's syndrome is a pathological condition where surgery may be lifesaving. The proper diagnosis depends upon the hormonal pattern of the patient, various dynamic tests and imagistic investigations. We report a case of a patient with Cushing's syndrome, with bilateral adrenal tumors and a pituitary microadenoma.

Giant adrenal cyst: case study.

One of the rarest situations regarding an adrenal incidentaloma is an adrenal cyst. We present the case of a 61-year-old male patient diagnosed with peritonitis. During surgery, a right adrenal tumor of 2 cm is discovered.

Premenstrual dysphoric disorder: neuroendocrine interferences.

Premenstrual dysphoric disorder (PMDD) consists in severe cognitive and mood changes, more aggressive as seen in premenstrual syndrome (PMS). These two syndromes are situated at the border between gynecology and psychiatry but the link between the two domains remains the neuroendocrine underlying mechanisms. In present, there are some molecular systems certainly proved as being involved, like estrogens.

Pheochromocytoma--from endocrinologist to surgeon.

We report the case an asymptomatic patient who underwent left adrenalectomy for a incidentally discovered large, cystic adrenal tumor. The patient presented no hypertension before or during the intervention. The hystopatological exam revealed a pheochromocytoma, with signs suggesting malignancy.

Pituitary incidentalomas--how often is too often?

Introduction: Clinical nonfunctional pituitary microadenomas, also known as incidentalomas are accidental observations made due to the application of high resolution imaging techniques as computed tomography or magnetic resonance. There are no standards regarding the follow-up of these tumors and taking into account their increased frequency among general population (during the last years they were based on the high performances of the imaging methods), we decided to study their dimensions and their evolution over time. We have also analysed their behavior with respect to their endocrine phenotype and the minimum period of time needed for the repetition of the imagistic procedure.

Galactocele and prolactinoma--a pathogenic association?

A galactocele is a rare form of cystic, benign lesion of the breast, appearing when a mammary duct becomes obstructed and over filled with milk. It is usually found in postpartum women, either lactating or not. There are only a few cases reported that are not immediately linked to the lactation, as seen in postmenopausal women or in men.

Cyanine dye N744 inhibits tau fibrillization by blocking filament extension: implications for the treatment of tauopathic neurodegenerative diseases.

Tau fibrillization is a potential therapeutic target for Alzheimer's and other neurodegenerative diseases. Small molecules capable of both inhibiting aggregation and promoting filament disaggregation have been discovered, but knowledge of their mechanism of action and potential for testing in biological models is fragmentary. To clarify these issues, the interaction between a small-molecule inhibitor of tau fibrillization, 3,3'-bis(beta-hydroxyethyl)-9-ethyl-5,5'-dimethoxythiacarbocyanine iodide (N744), and full-length four-repeat tau protein was characterized in vitro using transmission electron microscopy and fluorescence spectroscopy.

Triggers of full-length tau aggregation: a role for partially folded intermediates.

Alzheimer's disease is characterized in part by the accumulation of full-length tau proteins into intracellular filamentous inclusions. To clarify the events that trigger lesion formation, the aggregation of recombinant full-length four-repeat tau (htau40) was examined in vitro under near-physiological conditions using transmission electron microscopy and spectroscopy methods. In the absence of exogenous inducers, tau protein behaved as an assembly-incompetent monomer with little tertiary structure.

Pathways of tau fibrillization.

New methods for analyzing tau fibrillization have yielded insights into the biochemical transitions involved in the process. Here we review the parallels between the sequential progression of tau fibrillization observed macroscopically in Alzheimer's disease (AD) lesions and the pathway of tau aggregation observed in vitro with purified tau preparations. In addition, pharmacological agents for further dissection of fibrillization mechanism and lesion formation are discussed.

Ligand-dependent inhibition and reversal of tau filament formation.

Alzheimer's disease is defined in part by the intraneuronal accumulation of filaments comprised of the microtubule associated protein tau. Because animal model studies suggest that a toxic gain of function accompanies tau aggregation in neurons, selective pharmacological inhibitors of the process may have utility in slowing neurodegeneration. Here, the properties of a candidate small molecule inhibitor of tau fibrillization, 3-(2-hydroxyethyl)-2-[2-[[3-(2-hydroxyethyl)-5-methoxy-2-benzothiazolylidene]methyl]-1-butenyl]-5-methoxybenzothiazolium (N744), were characterized in vitro using transmission electron microscopy.

Evidence for an intermediate in tau filament formation.

Alzheimer's disease is defined in part by the intraneuronal accumulation of filaments comprised of the microtubule-associated protein tau. In vitro, fibrillization of full-length, unphosphorylated recombinant tau can be induced under near-physiological conditions by treatment with various agents, including anionic surfactants. Here we examine the pathway through which anionic surfactants promote tau fibrillization using a combination of electron microscopy and fluorescence spectroscopy.