Tawseef Ahmad

The presence of nerves within tumors was largely unexplored in the early 19 th and 20 th century, with contemporary pathology texts generally considering tumors to be devoid of nerves. However, observations of tumor-associated pain and intratumoral nerve fibers challenged this view, prompting questions about their role in neoplastic tissue. As early as 1897, Young Y. reported nerves in various non-neural tumors, including breast and cervical carcinomas, sarcomas, myxomas, and metastatic carcinomas, providing early histological evidence of neural elements within tumors (1). This seminal study raised an important question of whether intratumoral nerves represented pre-existing neural structures incorporated during tumor growth or reflected active neural changes associated with neoplastic development.To address this question, investigations in the late 1920s and early 1930s began to explore the origin and biological significance of these intratumoral nerves. In 1928, Herzog E. investigated the presence of nerve fibers in 100 neoplasms and proposed that intratumoral nerves represented pre-existing nerves incorporated into infiltrating neoplastic tissue. His observations suggested that the distribution of nerves was related to the pattern of tumor invasion, supporting the view that their presence could result from the incorporation of normal neural structures during tumor growth (2). In 1929, Oertel H. proposed a different interpretation, proposing that human carcinomas possessed an intrinsic neural organization, with nerve fibers closely associated with the tumor stroma, blood vessels, and parenchymal elements. This raised the possibility that the relationship between nerves and tumors might extend beyond passive entrapment (3). In 1930, Martynow W. further challenged the concept of simple nerve incorporation by suggesting that nerve fibers within carcinomas could be newly formed. He also described degenerative changes in these fibers, indicating that intratumoral nerves might undergo active remodeling in response to the tumor microenvironment (4).In 1931, Oertel H., Nye H., and Thomlinson B. provided additional observations on nerve fibers within human tumors, further supporting the presence of an organized neural component within neoplastic tissue (5). In 1933, Ryrie synthesized these observations in his original investigation of the anatomical and physiological relationship between nerve fibers and neoplasms. He considered several possibilities, including the incorporation of pre-existing nerves into tumors, the formation of new nerve fibers within neoplastic tissue, and degenerative and regenerative changes resembling those observed after peripheral nerve injury. These observations raised the possibility of an active interaction between nerves and malignant tissue. Nevertheless, Ryrie G. concluded that the available evidence did not justify assuming a trophic influence of nerves on malignant cells (6).Two studies published in 1982 and 1985 investigating neuroendocrine biomarkers also provided early biochemical evidence linking neural biology and cancer, demonstrating significantly elevated serum neuron-specific enolase (NSE) levels in patients with small-cell lung cancer (SCLC) (7,8). In 1982, Carney et al. first reported that serum NSE was elevated in 69% of newly diagnosed patients with SCLC (n = 94) compared with controls, with a higher prevalence in extensive-stage disease (87%) than limited-stage disease (39%). Mean NSE levels were significantly higher in extensive-stage disease (59 ng/ml vs 13.8 ng/ml), increased further with metastatic burden (84% of patients with 1-2 sites and 100% of those with ≥3 sites), and showed a strong correlation with chemotherapy response. SCLC cell lines derived from patients also consistently expressed high levels of NSE (7). In a comparable study, Akoun et al. found that serum NSE levels were elevated in 65.1% of patients diagnosed with SCLC (n = 43), with significantly higher mean levels in extensive-stage disease (50 ng/ml) than in limited-stage disease (16 ng/ml), while levels were much lower in non-SCLC (11 ng/ml) and noncancerous lung disease (7 ng/ml). NSE closely correlated with tumor burden and showed dynamic changes during chemotherapy, with higher early levels (>100 ng/ml) associated with better treatment response (8). This mechanism was subsequently revealed in a 2022 study (Figure 1), which demonstrated that NSE interacts with and suppresses neuroblastoma suppressor of tumorigenicity 1 (NBL1), thereby relieving NBL1-mediated inhibition of BMP2 signaling. This interaction enhances BMP2-BMPR1A signaling and activates the BMP2/Smad/ID1 pathway, ultimately promoting malignant characteristics of SCLC (9). Keeping track of these conceptual advances, a growing body of experimental evidence (detailed in section 2) have provided evidence of functional neuron-tumor interactions across multiple cancer types. Studies in human specimens have identified such interactions in squamous cell carcinoma (10), breast cancer (11), gastric cancer (12), pancreatic ductal adenocarcinoma (13), lung adenocarcinoma (14), prostate cancer (15), and diffuse midline glioma (16,17). SCLC has been investigated using human specimens, ex vivo electrophysiological and co-culture models (18), and in vivo models (19), while glioblastoma (20,21), glioma (22), diffuse midline glioma (16), gastric cancer (23), and breast-to-brain metastasis (24), have been studied primarily using in vitro and in vivo models. Evidence from these studies shows that neural signaling influences tumor growth, invasion, metastasis, and proliferation, while inhibition through pharmacological or genetic targeting of CHRM3, AMPARs, NMDARs/GRIN2B, GRIN2D, GABA receptors, NKCC1, CGRP, β-adrenergic signaling, and sensory or sympathetic neuron ablation has demonstrated therapeutic potential (12,18,22,23,25).Several recent reviews have synthesized the rapidly expanding field of cancer...

Mesalamine, a Biopharmaceutics Classification System (BCS) Class IV drug, exhibits poor solubility and low permeability, posing considerable challenges for accurate quantification. The aim of this study was to develop and validate a robust, cost-effective, and environmentally sustainable UV-visible spectrophotometric method for the precise quantification of mesalamine in ethanol and phosphate-buffered saline (PBS, pH 7.4), in accordance with International Council for Harmonisation (ICH) Q2(R1) guidelines. The method was optimized at a maximum absorption wavelength of 300 nm and validated with respect to linearity, accuracy, precision, specificity, and sensitivity through the determination of the limits of detection (LOD) and quantification (LOQ). Calibration curves were constructed over a concentration range of 10–100 µg/mL. The proposed method demonstrated excellent linearity, with a correlation coefficient (R²) of 0.99. Relative standard deviation (%RSD) values remained below 0.5%, indicating good repeatability and reproducibility. Accuracy was confirmed by recovery values ranging from 99.3% to 101.9%. The calculated LOD and LOQ values for mesalamine in ethanol (10.0 and 21.1 µg/mL, respectively) and PBS (6.8 and 20.6 µg/mL, respectively) were within acceptable limits according to ICH recommendations, confirming the sensitivity and reliability of the analytical method. The validated UV-visible spectrophotometric method provides a rapid, reliable, and cost-effective approach for the routine quantification of mesalamine during formulation development and pharmaceutical quality control. Owing to its simplicity and resource-efficient nature, the method represents a practical alternative to more complex chromatographic techniques. Further studies may broaden its applicability through integration with advanced analytical approaches in pharmaceutical sciences.

A broad-spectrum antibiotic known as piperacillin is often used with tazobactam to treat infections caused by anaerobic bacteria as well as different Gram-positive and Gram-negative bacteria. To ensure efficacy, it is important that piperacillin must reach therapeutic levels in the blood. An optimized, high-pressure liquid chromatography (HPLC) serves as an ideal technique for accurate drug concentration analysis. In the current study, a validated reverse-phase HPLC method was developed for the determination of piperacillin in pharmaceutical formulation and human plasma. Acetonitrile was used to deproteinized the plasma samples, vortexed them, and reconstituted the supernatant with the mobile phase prior to HPLC injection. The analysis was performed by using a Waters Alliance HPLC system, which had a UV detector set at 218 nm and a flow rate of 1 mL min ⁻¹ . The mobile phase consisted of methanol, water, tetrabutylammonium chloride buffer, and phosphoric acid. The method showed linearity from 0.5 μg mL ⁻¹ to 400 μg mL ⁻¹ , with 99.9% recovery rate. The detection and quantification limits were 0.25 μg mL ⁻¹ and 0.5 μg mL ⁻¹ , respectively. The Cmax exhibits variability among patients, even when the same dose is administered to adult individuals. The method is both accurate and reliable, and the findings highlights the importance of individualized dosing based on variations in patients' plasma concentrations.

The dispensing of non-prescription antibiotics is a worldwide concern, and antibiotics should only be dispensed with a legitimate prescription. A cross-sectional study was conducted using the simulated client methodology, with data collected, recorded, and analyzed using SPSS. The simulated client visited 210 pharmacies, of which 70 dispensed antibiotics without a prescription. Outcomes The most often suggested antibiotics for upper respiratory tract infections (URTIs) were Amoxicillin (n = 17, 8.1%), Clarithromycin (n = 20, 9.5%), and Moxifloxacin (n = 13, 6.2%), with 33.3% of medications dispensed without a prescription for URTIs. Cefixime (n = 20, 9.5%) and ceftriaxone (n = 17, 8.1%) were the most often administered medications for urinary tract infections (UTIs). The non-prescribed dispensing of upper respiratory tract infections (URTIs) and urinary tract infections (UTIs) was markedly elevated (p < 0.05). Antibiotics were dispensed without a prescription for diarrheal diseases in over 50% of pharmacies, with Metronidazole (n = 23, 11%), Azithromycin (n = 16, 7.6%), and Rifaximin (n = 15, 7.1%) being the most often prescribed. In all bivariate and multivariate models, male gender was associated with reduced likelihood (COR: 0.30, 95% CI: 0.12–0.72; p = 0.0079 and AOR: 0.03, 95% CI: 0.005–0.15; p = 0.0001). Individuals aged 30 years and older exhibited increased odds of dispensing in both bivariate (COR: 3.67, 95% CI: 1.69–8.87; p = 0.0018) and multivariate analyses (AOR: 9.44, 95% CI: 2.55–61.70; p = 0.001). The presence of a pharmacist on duty markedly diminished the likelihood of administering antibiotics without a prescription (COR: 0.13, 95% CI: 0.06–0.25; p = < 0.001; AOR: 0.06, 95% CI: 0.03–0.16; p = < 0.001). These findings highlight the imperative of enforcing existing laws and implementing rigorous rules, alongside pharmacy-centered antimicrobial stewardship programs that focus on accurate dispensing practices to mitigate antimicrobial resistance.

Background: Stroke is the second leading cause of death and disability worldwide. Global stroke rates rise with age. Socioeconomic factors make low- and middle-income youth more susceptible to stroke. Objectives: This study assessed many strokes incidence and predictive factors in Pakistan. Methodology: Stroke cases were studied at Peshawar Postgraduate Hospital. The study comprised consenting patients with recent first-time or recurrent strokes without secondary causes. Results: Our study found that strokes are more common in men (88%) and those over 63. The satisfied income group (72%) and urban population (60%) were the most affected. Ischemic type affected 84% of these cases. Anatomical MRI data shows that a stroke can impact any brain region. Hypertension (55%), with a mean blood pressure of 136/84 and 109/67mm Hg in male and female patients, respectively, was the main risk factor for stroke. Stroke victims' lipid levels were mostly normal. Aspiration pneumonia occurred in 19% of stroke patients. Blood chemistry assays for haemoglobin, total lymphocyte count, blood urea, alkaline phosphatase, and random blood sugar showed significant alterations. 28%, 47%, and 5% of patients' prescription regimens had minor, major, and severe interactions, respectively. Conclusion: Our study found that urban Khyber Pakhtoon Khwa inhabitants have a higher stroke risk than rural residents. These patients had mostly ischemic strokes. This paper summarizes stroke demographics, kinds, and interactions to help discover effective treatments for this potentially fatal disorder.

The traditional use of Mirabilis jalapa L. roots to enhance male sexual performance prompted us to assess the in silico, in vitro, and in vivo aphrodisiac activities of its hydroethanolic extract using normal male rats. Spectroscopic characterization indicated the presence of ß-D-glucopyranoside, methyl-1,9-benzyl-2,6-dichloro-9H-purine, and Bis-(2-ethylhexyl)-phthalate; these compounds have a significant inhibitory effect on the phosphodiesterase-5 (PDE-5) enzyme in silico evaluation and minerals (including zinc, cadmium, and magnesium). Other phytochemical analyses revealed the presence of phenolic compounds and flavonoids. These phytochemicals and minerals may contribute to the aphrodisiac activities of the extract. Additionally, the in vivo study revealed that the administration of M. jalapa root extract (300 mg/kg) significantly enhanced (p < 0.01, p < 0.03) mount, intromission, and ejaculation frequencies while significantly (p < 0.05) decreasing the mount and intromission latencies, as well as the post-ejaculatory interval time, in comparison with the standard drugs sildenafil and ginseng, resulting in enhanced erection and sexual performance in the rats. Furthermore, the extract significantly (p < 0.05) increased penile reflexes and also elevated the levels of testosterone and luteinizing hormones. Extract (300 mg/kg) significantly (p < 0.05) inhibited the PDE-5 enzyme in an in vitro study. Concludingly, the comprehensive findings of this study suggest that a standardized herbal extract derived from M. jalapa roots alleviates erectile dysfunction and premature ejaculation in male rats. M. jalapa root extract proved to be an alternative treatment for erectile dysfunction and premature ejaculation.