Nebivolol-Loaded Microsponge Gel for Healing of Diabetic Wound.

An attempt was made to formulate nebivolol-loaded microsponge gel to access drug at wound area, incorporated into gel that possess optimum moist wound management environment during later stages of wound closure. Nebivolol, antihypertensive drug, exhibits vasodilating effects via nitric oxide pathway, slows diabetic neuropathy, and restores endothelial function in diabetic wounds. Microsponges were prepared by optimizing independent variables; drug to polymer ratio and internal phase volume and their effects on production yield, entrapment efficiency, and particle size. Formulations of microsponges were evaluated for drug content. Differential scanning calorimetry indicated reduction in crystallinity of NB during the formation of microsponges. In vitro study (drug to polymer 1:4 and 10 ml internal phase volume acetone) showed 80% drug released within 8 h. Spherical and porous microsponges confirmed by scanning electron microscopy were incorporated in the carbopol 934 (2%) gel base. Gel was characterized for pH, viscosity, and drug content. Less spreadability determined by texture analyzer demonstrated viscous nature of gel. In vitro diffusion study revealed entrapped drug in porous microsponges with slow release to heal wound. In vivo study performed using streptozotocin-induced diabetic rats and excision wound model showed wound healing and closure activity within day 10. Histology revealed inflammatory cell infiltrations and neovascularization in granulation tissues, ultimately healing wound. Microsponge gel prolonged drug release due to entrapped form in porous structure of microsponges with significant and fast wound healing and closure in diabetic rats. Microsponges with loaded drug fulfilled accessibility at wound area, while gel provided optimum moist wound management environment during later stages of wound closure.

Rational Drug Discovery for Isoxazole Based VEGFR2 Inhibition.

BACKGROUND: Inhibiting receptor-tyrosine-kinase (RTK) signalling pathways has emerged as a key focus of novel cancer therapy development. Vascular endothelial growth factor receptor (VEGFR) is a member of the RTK family and is required for vasculogenesis and angiogenesis. Because VEGFR 2 is the subtype responsible for cellular angiogenesis and vasculogenesis, blocking it will impair tumour cell blood supply, reducing their development, proliferation, and metastasis. AIM & OBJECTIVE: The aim of this study is to obtain an optimised pharmacophore as a VEGFR2 inhibitor using QSAR investigations. This aids in determining the link between structure and activity in new chemical entities (NCEs). MATERIALS AND METHODS: The multi-linear regression approach (MLR) method was utilised to generate the QSAR Model using the programme QSARINS v.2.2.4. RESULTS AND DISCUSSION: For 2D QSAR, the best models produced has correlation coefficients of R2= 0.9396. The 3D-QSAR model obtained with R2= 0.9121 and Q2 = 0.8377. Taking docking observations, pharmacological behaviour, and toxicity analyses into account, most of the derivatives demonstrated VEGFR2 inhibitory competence. CONCLUSION: According to QSAR studies, more electron-donating groups on the benzene ring linked to the isoxazole were shown to be necessary for activity. In molecular docking studies, most compounds have shown stronger affinity for the crucial amino acids Cys:919, Asp:1046, and Glu:885, which are found in typical drugs. All NCEs passed the Lipinski screening.

The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseases.

BACKGROUND: As new infectious diseases (ID) emerge and others continue to mutate, there remains an imminent threat, especially for vulnerable individuals. Yet no generalizable framework exists to identify the at-risk group prior to infection. Metabolomics has the advantage of capturing the existing physiologic state, unobserved via current clinical measures. Furthermore, metabolomics profiling during acute disease can be influenced by confounding factors such as indications, medical treatments, and lifestyles. METHODS: We employed metabolomic profiling to cluster infection-free individuals and assessed their relationship with COVID severity and influenza incidence/recurrence. FINDINGS: We identified a metabolomic susceptibility endotype that was strongly associated with both severe COVID (ORICUadmission = 6.7, p-value = 1.2 × 10-08, ORmortality = 4.7, p-value = 1.6 × 10-04) and influenza (ORincidence = 2.9; p-values = 2.2 × 10-4, ßrecurrence = 1.03; p-value = 5.1 × 10-3). We observed similar severity associations when recapitulating this susceptibility endotype using metabolomics from individuals during and after acute COVID infection. We demonstrate the value of using metabolomic endotyping to identify a metabolically susceptible group for two-and potentially more-IDs that are driven by increases in specific amino acids, including microbial-related metabolites such as tryptophan, bile acids, histidine, polyamine, phenylalanine, and tyrosine metabolism, as well as carbohydrates involved in glycolysis. INTERPRETATIONS: These metabolites may be identified prior to infection to enable protective measures for these individuals. FUNDING: The Longitudinal EMR and Omics COVID-19 Cohort (LEOCC) and metabolomic profiling were supported by the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health.

Dural Ectasia and Cauda Equina Syndrome: A Rare Complication of Long-standing Fusion.

The clinicoradiological combination of cauda equina syndrome (CES) and dural ectasia is rare and has been described in a few of patients with ankylosing spondylitis (AS). Simultaneous occurrence of these entities in the absence of AS and in patients with long-standing spinal fusion is extremely rare. We present a case of dural ectasia and CES occurring as a long-term complication of instrumented spinal fusion and discuss the pathogenesis, imaging findings, and management options of this elusive disease process.

Comparative assessment of salivary cotinine level and psychological dependence among tobacco users.

BACKGROUND: The aim of the study was to assess the correlation between salivary cotinine level and psychological dependence measured through Fagerstrom test for nicotine dependence (FTND) questionnaire among tobacco users. MATERIALS AND METHODS: This was a cross-sectional study, conducted on tobacco users. Participants with the present habit of tobacco chewing and smoking above the age of 16 years were included in the study. A standard questionnaire form of FTND revised version for smoking and smokeless form of tobacco were given to each participant. Each participant was asked to answer the questions as per their experience of tobacco consumption and calculate the total point score or FTND score. Salivary cotinine level assessment was done using commercial available NicAlert kit. RESULTS: When salivary cotinine level was correlated with different variables of both groups, it was observed that weak correlation between salivary cotinine level and FTND scoring in smokers group (r = 0.083) and also in smokeless group (r = 0.081). When two groups were compared for salivary cotinine level, statistically significant difference (P = 0.021) was observed, with smokeless group showing high level of salivary cotinine level as compared to smokers group. CONCLUSION: Salivary cotinine and psychological dependence through FTND scoring are not strongly correlating with each other. This indicates that dependence over tobacco is a separate phenomenon and cannot be assessed by salivary cotinine level. It is well accepted that salivary cotinine level is influenced by age of individual, duration of habit, and type of tobacco consumption.

Transient Reversal of a Face Turn (an Abnormal Head Posture, AHP) due to Manifest Latent Nystagmus, after Eye Muscle Strabismus Surgery for the Associated Infantile Esotropia.

Patients with infantile esotropia and manifest latent nystagmus adopt a face turn towards the fixing eye as a nystagmus dampening mechanism. The surgical plan should aim to correct both the face turn and the strabismus. Reversal of the face turn after surgery for the strabismus can be (i.e. was) distressing for both the surgeon and the patient and has not been reported previously to the best of our knowledge. We report our patient with a transient reversal of face turn after surgery.