Pakistan journal of pharmaceutical sciences最新文献

The predictiveness and diagnostic utility of thyroid antibodies-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody and anti-thyroid peroxidase antibody-were investigated in autoimmune thyroid disease. The charts of 85 patients with Hashimoto's thyroiditis or Graves' disease were retrospectively analyzed with causal inference techniques and machine learning algorithms to estimate adjusted associations and interactions among antibodies. The most robust estimated disease diagnosis association was with anti-thyroid peroxidase antibody (mean treatment effect = 0.731) which also gave the best predictive accuracy (area under the receiver operating characteristic curve = 0.875) especially in the middle-aged and older population. Predictive accuracy was enhanced by using several antibodies (area under the curve = 0.913) whereas, interaction effects were trivial. Thyroid-stimulating hormone receptor antibody positivity was highly predictive of the clinical decision to start Methimazole treatment in Graves' disease. The findings suggest that anti-thyroid peroxidase antibody preference for screening and thyroid antibody profile use in treatment planning can guide clinical decision-making, within the constraints of causal inference assumption employed.

Urinary tract infections (UTIs) remain the most frequent clinical diagnosis and Vancomycin-resistant Enterococci (VRE) second-leading cause of UTIs. The aims of this study were to ascertain the patterns and prevalence of UTIs in Sindh and underlying resistance mechanisms for VRE. Bacterial colonies were identified traditionally from a total of 33272 urine samples. Enterococcus species were identified using Facklam and Collins scheme. Antibiotic susceptibility was determined by Kirby-Bauer method and minimum inhibitory concentration (MIC) by E-test. VRE phenotypes were checked using vancomycin and teicoplanin discs. UTIs prevalence during November-2022 to December-2023 is 22%. Reproductive-age women and elders affected most. Predominant Gram-negative pathogens were Escherichia coli (47.6%), Klebsiella spp. (15.7%), Pseudomonas aeruginosa (13.3%) and Morganella morganii (9.3%) while Enterococci were the leading Gram-positive pathogen (46%). E. faecium was the most prevalent (74.8%) followed by E. faecalis and motile Enterococci. VRE were noted 16.3%. All Enterococci were resistant to cefotaxime, ampicillin and co-amoxiclav and susceptible to linezolid. Each E. faecium was VanA phenotype while 20% E. faecalis were VanB phenotype. Vancomycin-resistance has increased by two-fold in Pakistan. The negligent-opportunistic M. morganii has emerged the fourth-leading cause of UTIs. We recommend focusing on VanRS system, a potential target of novel therapeutics for VRE.

Sleep disorders in elderly type 2 diabetes mellitus (T2DM) patients worsen metabolic dysfunction. This study assessed resistance exercise plus metformin on glycemic stability and sleep quality in 180 elderly T2DM patients with sleep disturbances, divided into metformin alone (control) or metformin plus resistance exercise (intervention) for 12 weeks. Primary outcomes [fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), glycosylated hemoglobin (HbA1c), pittsburgh sleep quality index (PSQI) scores, electroencephalogram (EEG)-measured sleep architecture] and secondary outcomes [fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), melatonin levels] were evaluated at baseline, 6 and 12 weeks. Baseline characteristics were similar (P>0.05). The intervention group showed greater reductions in FBG, 2hPG and HbA1c (P<0.05), along with significant PSQI score improvements (P<0.05) and better sleep architecture (P<0.05). Fasting insulin and HOMA-IR decreased in both groups but were lower in the intervention group (P<0.05). Melatonin increased only in the intervention group (P<0.05). No major adverse effects were observed. Resistance exercise combined with metformin enhances glycemic control and sleep quality in elderly T2DM patients, supporting nonpharmacologic interventions as valuable adjuncts in diabetes management.

This study investigated the impact of vitamin D (VD) combined with thermotherapy and resistance exercise (RE) on elderly patients with sarcopenia, thereby offering novel insights into evidence-based management strategies for sarcopenia. 140 sarcopenia patients were admitted between May 2023 and August 2024. Participants were randomized to receive either VD combined with thermotherapy and resistance exercise (treatment group) or thermotherapy and resistance exercise alone (control group). Skeletal muscle mass and handgrip strength were evaluated before and after the intervention using a body composition analyzer and a hand dynamometer. In addition, the levels of blood glucose, blood lipids, inflammatory factors and thyroid hormones were measured. Both groups exhibited significant improvements in skeletal muscle mass, handgrip strength and glucose/lipid metabolism post-treatment, with the treatment group demonstrating superior enhancements (P<0.05). After treatment, the level of inflammatory factors in the treatment group was lower, while the level of thyroid hormone was higher (P<0.05). There was a significant negative correlation between 25-hydroxyvitamin D3 [25(OH)D3] and myostatin (MSTN) in both groups (P<0.05). The combination of VD with thermotherapy and RE effectively enhances skeletal muscle function, suppresses inflammatory responses and regulates endocrine function in elderly patients with sarcopenia.

Blood transfusion planning in traumatic brain injury (TBI) is ideal and pharmacotherapy such as tranexamic acid (TXA) may influence transfusion requirement. Within this retrospective, single-center case-control study, 259 TBI patients who were admitted from January 2022 to December 2024 were randomly allocated into training (70%) and validation (30%) datasets. Demographic, clinical, laboratory, surgical and pharmacologic variables-like TXA-were evaluated using univariable and multivariable logistic regression for independent predictors of transfusion. Surgery, tracheal intubation, longer hospital stay, lower hemoglobin and TXA administration were independent predictors of transfusion. The TXA nomogram had high discrimination (AUC 0.94 training; 0.93 validation), good calibration and clinical utility as demonstrated by decision curve analysis. Higher TXA use in transfused patients is likely due to confounding by indication, as patients were more ill and more likely to receive TXA. The inclusion of TXA in predictive models enhances personalized risk prediction of transfusion, but the model remains hypothesis-generating and requires external multicenter verification before being used clinically. This study is supportive of the development of pragmatic, pharmacology-driven tools for early risk stratification and precision transfusion planning in TBI.

Endophytic fungi live inside healthy plant tissues and have become common plant partners. These fungi not only help plants grow and produce pigments, enzymes and bioactive compounds, but they can also harm plant tissues and produce toxins. They are found in various parts of plants, such as stem, shoot, root, leaves and bark. Sunflower (Helianthus annuus L.) is a universal host for many species of endophytic fungi, which possess unique medicinal properties. This study aimed to isolate, identify and analyze the biochemical characteristics of endophytic fungi from sunflower. Sunflower (Helianthus annuus L.) plant was collected and chopped into smaller pieces and put on potato dextrose agar (PDA) medium for fungal growth. Fungi were separated, cleaned and maintained in a continuous subculture. After morphological and molecular identification sample was subjected to biochemical profiling by FTIR. Results showed the presence of Rhizopus sp., Cladosporium sp., Penicillium sp. and Aspergillus sp. in sunflower and structural determination by FTIR showed a number of bands and peaks.

This study constructed a chain analysis model linking pharmaceutical attributes, physician preferences, clinical efficacy and pharmacoeconomic outcomes. Using multicenter prospective data, we analyzed the multi-level mechanisms influencing the key pharmaceutical attributes of emergency trauma hemostatics. A total of 1,500 patients from six hospitals in China were included. The pharmacological properties of tranexamic acid, ethamide and hemocoagulase were analyzed and their impact on physician preferences, efficacy and economic outcomes was assessed. Results showed that antifibrinolytic mechanism (weighted 38.2%), onset of action (29.7%) and thrombotic risk (24.1%) were the core attributes influencing physician preferences. Due to its advantageous pharmaceutical attributes, tranexamic acid had the shortest hemostatic time (14.5 ± 3.0 minutes), the lowest 24-hour blood transfusion volume (320 ± 70 ml) and the best cost-effectiveness (328.6 yuan/minute). This study provides evidence-based guidance for the precise selection of hemostatics based on pharmaceutical attributes.

Tuberculosis, being an infectious disease, is unchecked and still hard to wipe out in the underdeveloped countries. Despite ongoing efforts, no new TB vaccine has been successfully developed in the past century beyond BCG, although DNA-based vaccines have shown promise over the last two decades. In this study, five Mycobacterium tuberculosis-specific genes- Rv1908c/KatG, Rv3418c/GroES, Rv0934/PhoS1/PstS, Rv0440/GroEL2 and Rv0350/DnaK-were cloned into the pVAX1 expression vector to construct DNA vaccines. These constructs were evaluated in rats using naked DNA and BCG prime-boost strategies. Forty-five Wistar albino rats were divided into three major groups: DNA vaccine group, BCG prime-boost group and no vaccine control. Post-immunization responses were evaluated through cytokine ELISA for TNF-α, IFN-γ and IL-6. Among DNA vaccines, DnaK-pVAX1 and GroES-pVAX1 elicited the strongest cytokine responses, followed by GroEL2-pVAX1 and PstS-pVAX1. The prime-boost groups (especially BCG + DnaK-pVAX1, BCG + GroES-pVAX1 and BCG + cocktail) showed further enhanced responses. Statistical analysis confirmed significant cytokine elevation in vaccinated groups compared to controls (p < 0.05). DNA vaccines, whether used alone or in combination with BCG, show strong potential as immunogenic and therapeutic tools for TB and may help reduce treatment duration in the future.

Salvia przewalskii Maxim. is a traditional Chinese herbal medicine which has long been used for the treatment of cardiovascular diseases in China. The current study aimed to investigate the neuroprotective effect of Salvia przewalskii extract of total phenolic acids (SPE) in a rat model of acute spinal cord injury (ASCI). Quantitative analysis of the active constituents in SPE by HPLC showed that rosmarinic acid accounted for 34.32% and salvianolic acid B for 4.27%. The experiment with the ASCI rat model demonstrated that SPE did not have significant adverse effects on body mass on day 1 and 3 after drug administration. In addition, SPE treatment significantly enhanced the BBB scores, improved the inclined plane angles and increased the serum levels of oxidative stress markers SOD and GSH in ASCI rats. Concurrently, it reduced the serum levels of MDA and inflammatory cytokines TNF-α, IL-1β, IL-6, IL-17 and IL-18. SPE also mitigated neuronal damage within the spinal cord tissue by minimizing hemorrhage and preserving neuronal integrity. Mechanistically, SPE ameliorated neuronal damage in the spinal cord by attenuating oxidative stress and inflammatory responses, thereby facilitating the recovery of motor function in ASCI rats.

Gingivitis, affecting 50%-90% of the population, is characterized by red, swollen gums and bleeding. If untreated, it can progress to periodontitis. Azithromycin, a macrolide antibiotic, has anti-inflammatory properties by inhibiting the NF-κB pathway and reducing the release of inflammatory mediators such as IL-1β and TNF-α. This study investigates the effects of azithromycin-coated implants on gingival tissue healing in patients with gingivitis. Clinical indicators (gingival index, bleeding on probing, probing depth and mucosal redness and swelling) and cellular dynamics (Ki-67 positive cell rate, apoptosis rate and expression levels of Cyclin D1 and CDK4) were evaluated preoperatively and at 1 and 3 months postoperatively. The study found significant improvements in clinical indicators and cellular dynamics in the experimental group compared to the control group, indicating that azithromycin-coated implants effectively reduce inflammation and enhance cell proliferation and tissue healing.