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1.
Indian J Surg Oncol ; 15(2): 250-257, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38741650

ABSTRACT

Molecular sub-characterization of triple-negative breast cancer (TNBC) has great therapeutic and possibly prognostic implications. The primary aim of this study was to investigate the incidence of luminal androgen receptor (LAR) subtype of TNBC and secondary aims were sub-categorization and clinico-pathologic correlation of LAR breast cancers. Retrospective study (January 2008 and 31st of December 2018) consisting of 157 TNBC patients. Androgen receptor (AR) expression was measured by immunohistochemical analysis. One percent cutoff was set as a positive expression. Sub-categorization was done on the basis of EGFR (> 15% of tumor cells) and Ki-67 expression (low- < 11%, intermediate- 11-20%, and high- > 21%). AR expression was correlated with various clinico-pathologic features and outcomes of the patients. The incidence of AR expression in TNBC was 24.8%. Considering different thresholds of > 5%, > 10%, and > 20% immunostaining, the incidence of AR positivity was 18.4, 15.2, and 11.5% respectively. The incidence of Ki-67 (p = 0.89) and EGFR (p = 0.643) expression did not differ significantly in AR-positive and -negative TNBC. Based on EGFR expression 19, 67 and 14% patients were categorized as low, intermediate, and high risk respectively. Low-risk (p ≤ 0.001) and low-grade (p = 0.014) tumors were more likely to have > 10% AR expression. Clinico-pathological profile, response to neoadjuvant chemotherapy, disease-free survival (p = 0.458), and overall survival (p = 0.806) did not significantly differ between AR expressing and negative TNBC. On multivariate analysis, only tumor staging was a significant predictor of survival (p = 0.012) and AR expression of > 10% revealed a trend towards improved survival (p = 0.07). When considering only AR-positive TNBC, AR expression of > 10% (p = 0.038), distant metastases (p = 0.003), and EGFR status (p = 0.024) were significantly associated with survival. AR expression does not seem to very strongly correlate with prognosis in TNBC and further studies could focus more on its predictive role in deciding anti-androgen therapy.

2.
J Mass Spectrom ; 59(6): e5031, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38726684

ABSTRACT

Managing ocular microbial infections typically requires pharmacotherapy using antibiotic eye drops, such as moxifloxacin hydrochloride (MFX), combined with an antifungal agent like amphotericin B (AB). We carried out and validated an LC-MS/MS assay to quantify these compounds in rabbit tear fluid in order to look into the pharmacokinetics of these two drugs. We employed a protein precipitation technique for the extraction of drugs under examination. A Waters Symmetry C18 column was used to separate the analytes and internal standard. The composition of the mobile phase was like (A) 0.1% v/v formic acid in water and (B) methanol. The detection of MFX and AB was accomplished through the utilization of positive ion electrospray ionization under multiple reaction monitoring mode. The linearity curves for both analytes exhibited an acceptable trendline across a concentration range of 2.34-300 ng/mL for MFX and 7.81-1000 ng/mL for AB in surrogate rabbit tear fluid. The lower limit of quantitation for MFX was 2.34 ng/mL, while for AB, it was 7.81 ng/mL. The approach was strictly validated, encompassing tests of selectivity, linearity (with r2 > 0.99), precision, accuracy, matrix effects, and stability. Consequently, we employed this method to evaluate the pharmacokinetics profiles of MFX and AB in rabbit tear fluid following single topical doses.


Subject(s)
Moxifloxacin , Tandem Mass Spectrometry , Tears , Rabbits , Animals , Tandem Mass Spectrometry/methods , Tears/chemistry , Moxifloxacin/pharmacokinetics , Moxifloxacin/analysis , Reproducibility of Results , Amphotericin B/pharmacokinetics , Amphotericin B/analysis , Limit of Detection , Anti-Infective Agents/pharmacokinetics , Anti-Infective Agents/analysis , Chromatography, Liquid/methods , Ophthalmic Solutions/pharmacokinetics , Linear Models , Liquid Chromatography-Mass Spectrometry
3.
Article in English | MEDLINE | ID: mdl-38654153

ABSTRACT

Ocular disorders can lead to serious sight impairment and irreversible blindness. Generally simple topical and systemic treatments are recommended for treating these vision-threatening illnesses. The distinctive architecture of the eye complicates ocular drug delivery. The ophthalmic emulsion formulations have been found to increase bioavailability in the eye by prolonging residence time and improving permeability through the cornea. Therefore, this study highlights ophthalmic emulsions meant for both the anterior and posterior parts of the eye while examining a wide range of ocular disorders that affect individuals globally. This review presents, in brief, recent emulsion-based patented innovations, clinical trials, and marketed emulsion formulations for ocular drug delivery, which are strengthening development of the new ophthalmic drug products for managing different ocular diseases and disorders.

4.
Sci Rep ; 14(1): 9305, 2024 04 23.
Article in English | MEDLINE | ID: mdl-38653804

ABSTRACT

Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in CTCL cells. KPT-330 reduces cell proliferation, induces G1 cell cycle arrest and apoptosis. RNA-sequencing was used to explore the underlying mechanisms. Genes associated with the cell cycle and the p53 pathway were significantly enriched with KPT-330 treatment. KPT-330 suppressed XPO1 expression, upregulated p53, p21WAF1/Cip1, and p27Kip1 and their nuclear localization, and downregulated anti-apoptotic protein (Survivin). The in vivo efficacy of KPT-330 was investigated using a bioluminescent xenograft mouse model of CTCL. KPT-330 blocked tumor growth and prolonged survival (p < 0.0002) compared to controls. These findings support investigating the use of KPT-330 and next-generation XPO1 inhibitors in CTCL.


Subject(s)
Apoptosis , Cyclin-Dependent Kinase Inhibitor p21 , Cyclin-Dependent Kinase Inhibitor p27 , Exportin 1 Protein , Karyopherins , Lymphoma, T-Cell, Cutaneous , Receptors, Cytoplasmic and Nuclear , Triazoles , Tumor Suppressor Protein p53 , Humans , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Lymphoma, T-Cell, Cutaneous/drug therapy , Lymphoma, T-Cell, Cutaneous/pathology , Lymphoma, T-Cell, Cutaneous/metabolism , Lymphoma, T-Cell, Cutaneous/genetics , Apoptosis/drug effects , Animals , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cyclin-Dependent Kinase Inhibitor p21/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Cyclin-Dependent Kinase Inhibitor p27/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Karyopherins/metabolism , Karyopherins/antagonists & inhibitors , Mice , Cell Line, Tumor , Triazoles/pharmacology , Cell Proliferation/drug effects , Hydrazines/pharmacology , Hydrazines/therapeutic use , Xenograft Model Antitumor Assays , Signal Transduction/drug effects , Gene Expression Regulation, Neoplastic/drug effects
5.
Biopolymers ; : e23578, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38577865

ABSTRACT

Ocular drug delivery is constrained by anatomical and physiological barriers, necessitating innovative solutions for effective therapy. Natural polymers like hyaluronic acid, chitosan, and gelatin, alongside synthetic counterparts such as PLGA and PEG, have gained prominence for their biocompatibility and controlled release profiles. Recent strides in polymer conjugation strategies have enabled targeted delivery through ligand integration, facilitating tissue specificity and cellular uptake. This versatility accommodates combined drug delivery, addressing diverse anterior (e.g., glaucoma, dry eye) and posterior segment (e.g., macular degeneration, diabetic retinopathy) afflictions. The review encompasses an in-depth exploration of each natural and synthetic polymer, detailing their individual advantages and disadvantages for ocular drug delivery. By transcending ocular barriers and refining therapeutic precision, these innovations promise to reshape the management of anterior and posterior segment eye diseases.

6.
Ann Med Surg (Lond) ; 86(2): 678-688, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38333253

ABSTRACT

Introduction: Indocyanine green (ICG) angiography is the 'real-time intraoperative imaging' technique used to reduce the chances of hypoparathyroidism in post-thyroidectomy patients. In our study, the authors predicted the risk of early post-thyroidectomy hypocalcemia by intraoperative evaluation of parathyroid gland perfusion by ICG angiography. Materials and methods: In patients who underwent total thyroidectomy, ICG angiography was done using the SPY PHI imaging system (Stryker). Post-thyroid specimen removal, scoring of parathyroids was done in spy contrast mode. All 4 or <4 visualized parathyroids were scored for vascularity with the highest score of 8. Serum ionized calcium was done 6 h postsurgery and on the morning and evening of postoperative days 1 and 2. Calcium supplements were given to only those who developed clinical or severe biochemical hypocalcemia. Results: Out of 60, postoperative hypocalcemia was noted in 41 patients. Total ICG score ≤5 was seen in 34 patients, out of which 28 developed postoperative hypocalcemia showing PPV 82.3% and diagnostic accuracy of 68.3% while iPTH (4.28 pmol/l) showed PPV 76.7 and diagnostic accuracy 70 %. In eight patients, none of the glands was scored as 2 (White) and all these patients developed hypocalcemia requiring calcium infusion. Conclusion: The absence of visualization of at least 1 well-perfused (score 2) gland on ICG angiography is highly predictive of hypocalcemia and the majority of patients with total ICG score ≤5 developed hypocalcemia in the immediate postoperative period. ICG is a good predictor of the absence of hypoparathyroidism after thyroidectomy and is comparable to iPTH in the prediction of post-thyroidectomy hypocalcemia.

7.
Chem Biodivers ; 21(3): e202301389, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38299764

ABSTRACT

Pirfenidone, initially indicated for lung fibrosis, has gone beyond its original purpose, and shown promise in eye care. This detailed review tracks its evolution from lung treatment to aiding eye healing as evidenced by published literature. Pirfenidone's multifaceted attributes extend to mitigating corneal fibrosis, inflammation, and trauma. Through rigorous investigations, its efficacy emerges in diabetic retinopathy, macular degeneration, and postoperative glaucoma interventions. As an unheralded protagonist, pirfenidone reshapes ocular care paradigms, inviting renewed research opportunities.


Subject(s)
Pyridones , Wound Healing , Pyridones/pharmacology , Pyridones/therapeutic use
8.
World J Surg ; 48(3): 729-738, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38299448

ABSTRACT

BACKGROUND: Pediatric endocrine disorders requiring surgical intervention are rare and so are experienced surgeons dealing with these. The aim of the current study was to investigate disease profile and perioperative outcome of pediatric patients with surgical endocrine disorders in an endocrine surgery unit. METHODS: This retrospective study (Sep 1989-Aug 2019) consisted of pediatric endocrine surgery patients (<18 years) who were managed by a team of pediatric endocrinologists and endocrine surgeons at our center. Patients were divided into three cohorts consisting of a decade each. Clinico-pathologic variables, perioperative events operative and follow-up details were recorded. RESULTS: A total of 332 children were included and their mean age was 14.6 ± 3.9 years (M:F = 1:1.6). Thyroid disorders were most prevalent (59.8%), followed by adrenal (28.2%), parathyroid (10.4%), and pancreas (1.5%). Incidence of benign, malignant, and congenital/developmental disorders were 65.4, 28.1 and 8.3, respectively. Familial association was observed in 8.9% children, which is highest among pheochromocytoma patients. Overall, 201 thyroidectomies + associated procedures, 35 parathyroidectomies, 96 adrenal and paraganglioma resections, and 5 pancreatic procedures were performed. Median hospital stay was 5.6 ± 4.1 days. The number of cases increased significantly over 3 decades. Clinical profile and outcome did not vary except for significant decrease in incidence of malignant pathology (p = 0.04) and increase in VHL cases (p = 0.04) in the last decade though overall increase in familial cases was nonsignificant (p = 0.11). No perioperative mortality was observed except for 3% after adrenalectomy. CONCLUSION: A team of dedicated endocrine surgeons and pediatric endocrinologists is effective in management of pediatric endocrine surgery.


Subject(s)
Adrenal Gland Neoplasms , Endocrine Surgical Procedures , Endocrine System Diseases , Pheochromocytoma , Surgeons , Humans , Child , Adolescent , Retrospective Studies , Pheochromocytoma/surgery , Endocrine System Diseases/epidemiology , Endocrine System Diseases/surgery , Adrenal Gland Neoplasms/surgery
10.
Article in English | MEDLINE | ID: mdl-38199059

ABSTRACT

Arbortristoside-A (Arbor-A) is a naturally occurring iridoid glycoside and herbal-based lead molecule with proven medicinal potential. Aiming at the development of an efficient analytical tool for the quantification of Arbor-A in pharmaceutical dosage forms, in the presented work, we developed an economical, fast, and sensitive RP-HPLC-UV method and validated the procedure as per the ICH guidelines, Q2(R1). The chromatographic separation was accomplished under the optimised experimental conditions using an HPLC system with an LC-2010 autosampler, a PDA detector, and a Phenomenex C18 column with the mobile phase composed of a 70:30 (v/v) water-acetonitrile mixture eluting isocratically at a flow rate of 1 mL/min at ambient temperature, and UV detection at 310 nm. Arbor-A showed a sharp peak at the retention time of 5.60 min and exhibited linearity (R2 = 0.9988) with LOD and LOQ of 0.50 µg/mL and 1.50 µg/mL, respectively. The accuracy of the method was 98.33-101.36 % with acceptable intra-day and inter-day precisions as well as robustness (<2% RSD). To ratify the applicability of the presented approach in emerging pharmaceuticals, a nanoformulation loaded with Arbor-A was designed and analysed utilising the provided methodology. The method has also enabled to determine the degradation kinetics of Arbor-A under stress conditions, etcetera, employing forced degradation and short term stability studies.


Subject(s)
Chromatography, High Pressure Liquid , Iridoid Glucosides , Chromatography, High Pressure Liquid/methods , Limit of Detection , Drug Stability , Reproducibility of Results , Pharmaceutical Preparations
11.
Int J Neurosci ; : 1-3, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38180031

ABSTRACT

BACKGROUND: The Déjerine-Roussy syndrome is caused by a stroke in the posterior lateral nuclei of the thalamus. It has a 17 to 18% prevalence after a stroke involving the inferior lateral thalamus. METHODS: We reported a case of a 65-year-old, diabetic and hypertensive male who presented with sudden onset of superficial hemianesthesia, allodynia, severe and paroxysmal pain on the right side of the body with choreoathetoid movements in the upperN limb, along with slured speech, and unsteadiness while walking. CONCLUSIONS: It is characterized by superficial hemianesthesia, allodynia, severe paroxysmal pain, and choreoathetoid movements in the limbs on the paralyzed side. A posterior lateral thalamic lesion can present with ataxia hemiparesis contralateral to the side of the lesion.

12.
Article in English | MEDLINE | ID: mdl-38217969

ABSTRACT

A rationale poly-microbial keratitis (PMK) therapy requires quick identification of pathogen (bacteria and fungi) and their efficient treatment. However, majority of healthcare providers are still having trouble finding an effective medicine to treat PMK due to constraints such as antimicrobial resistance, dose and dosing schedule. Thus, a broad spectrum anti-fungal and antibacterial having less resistance in community involving combination therapy such as amphotericin B (AmB), tobramycin (TBR) and vancomycin (VCM) is required. Hence, to characterize the pharmacokinetic (PK) and PK-pharmacodynamic (PD) indices, a rapid and sensitive simultaneous LC-MS/MS bioanalytical method was developed and validated for the quantification of AmB, TBR and VCM in rabbit ocular biofluids and tissues. Chromatographic resolution was achieved on a Zorbax C18 column with a mobile phase composed of acetonitrile and 0.4 % formic acid in deionized water using a gradient mode of elution. The calibration curves showed good linearity over the concentration range of 1.95-500 ng/mL for AmB and TBR, 3.9-800 ng/mL for VCM, respectively. The lower limit of quantification (LLOQ) was found to be 1.95 ng/mL for AmB and TBR, and 4.5 ng/mL for VCM. Analyte extraction was performed by simple protein precipitation method with minimal sample volume of 10 µL. Finally, the developed method was validated for selectivity, linearity (r2 > 0.99), precision, accuracy, matrix effects, and stability. The ocular pharmacokinetic profile of commercial AmB, TBR, and VCM formulations was further assessed using the validated method and the PK-PD indices along with dosing frequency was predicted by PK-PD modelling using Phoenix WinNonlin Software.


Subject(s)
Amphotericin B , Keratitis , Animals , Rabbits , Chromatography, Liquid/methods , Tobramycin , Vancomycin , Liquid Chromatography-Mass Spectrometry , Tandem Mass Spectrometry/methods , Anti-Bacterial Agents , Keratitis/drug therapy , Reproducibility of Results , Chromatography, High Pressure Liquid/methods
13.
Dalton Trans ; 53(4): 1680-1690, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38167900

ABSTRACT

With increasing interest in nickel-based electrocatalysts, three heteroleptic Ni(II) dithiolate complexes with the general formula [Ni(II)L(L')2] (1-3), L = 2-(methylene-1,1'-dithiolato)-5,5'-dimethylcyclohexane-1,3-dione and L' = triphenylphosphine (1), 1,1'-bis(diphenylphosphino)ferrocene (DPPF) (2), and 1,2-bis(diphenylphosphino)ethane (DPPE) (3), have been synthesized and characterized by various spectroscopic techniques (UV-vis, IR, 1H, and 31P{1H} NMR) as well as the electrochemical method. The molecular structure of complex 2 has also been determined by single-crystal X-ray crystallography. The crystal structure of complex 2 reveals a distorted square planar geometry around the nickel metal ion with a NiP2S2 core. The cyclic voltammograms reveal a small difference in the redox properties of complexes (ΔE° = 130 mV) while the difference in the catalytic half-wave potential becomes substantial (ΔEcat/2 = 670 mV) in the presence of 15 mM CF3COOH. The common S^S-dithiolate ligand provides stability, while the rigidity effect of other ligands (DPPE (3) > DPPF (2) > PPh3 (1)) regulates the formation of the transition state, resulting in the NiIII-H intermediate in the order of 1 > 2 > 3. The foot-of-the-wave analysis supports the widely accepted ECEC mechanism for Ni-based complexes with the first protonation step as a rate-determining step. The electrocatalytic proton reduction activity follows in the order of complex 1 > 2 > 3. The comparatively lower overpotential and higher turnover frequency of complex 1 are attributed to the flexibility of the PPh3 ligand, which favours the easy formation of a transition state.

14.
J Ocul Pharmacol Ther ; 40(1): 13-33, 2024.
Article in English | MEDLINE | ID: mdl-37733327

ABSTRACT

Purpose: Diabetic retinopathy (DR) is a microvascular retinal disease associated with chronic diabetes mellitus, characterized by the damage of blood vessels in the eye. It is projected to become the leading cause of blindness, given the increasing burden of the diabetic population worldwide. The diagnosis and management of DR pose significant challenges for physicians because of the involvement of multiple biochemical pathways and the complexity of ocular tissues. This review aims to provide a comprehensive understanding of the molecular pathways implicated in the pathogenesis of DR, including the polyo pathway, hexosamine pathway, protein kinase C (PKC), JAK/STAT signaling pathways, and the renin-angiotensin system (RAS). Methods: Academic databases such as PubMed, Scopus, Google Scholar and Web of Science was systematically searched using a carefully constructed search strategy incorporating keywords like "Diabetic Retinopathy," "Molecular Pathways," "Pharmacological Treatments," and "Clinical Trials" to identify relevant literature for the comprehensive review. Results: In addition to activating other inflammatory cascades, these pathways contribute to the generation of oxidative stress within the retina. Furthermore, it aims to explore the existing pharmacotherapy options available for the treatment of DR. In addition to conventional pharmacological therapies such as corticosteroids, antivascular endothelial growth factors, and nonsteroidal anti-inflammatory drugs (NSAIDs), this review highlights the potential of repurposed drugs, phyto-pharmaceuticals, and novel pipeline drugs currently undergoing various stages of clinical trials. Conclusion: Overall, this review serves as a technical exploration of the complex nature of DR, highlighting both established and emerging molecular pathways implicated in its pathogenesis. Furthermore, it delves into the available pharmacological treatments, as well as the promising repurposed drugs, phyto-pharmaceuticals, and novel drugs currently being evaluated in clinical trials, with a focus on their specific mechanisms of action.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/etiology , Diabetic Retinopathy/pathology , Retina/pathology , Adrenal Cortex Hormones/therapeutic use , Oxidative Stress , Pharmaceutical Preparations , Diabetes Mellitus/drug therapy
15.
Head Neck ; 46(1): 37-45, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37860889

ABSTRACT

INTRODUCTION: Noise in the operating room is an ongoing problem that impacts the outcome of any surgery. Noise as a stressor can produce a startling reaction and activate the fight or flight response of the autonomic and endocrine systems. The psychobiology of stress as assessed by salivary cortisol level is a sensitive measure of allostatic load. This study aims to correlate, both subjectively and objectively, the salivary cortisol levels of the surgeon with noise level measurement in an endocrine surgery operating room (OR). MATERIALS AND METHODS: A prospective observational study was conducted in the Endocrine surgery OR of a tertiary care center. We recorded the noise from the shifting in of patients in the OR to shifting out using a digital sound level meter. The operating surgeon (S) provided two salivary cortisol samples (normal salivary cortisol <5 nmol/L), one baseline and another after the procedure. The questionnaire for the assessment of distraction during thyroidectomy was filled in by the S at the end of the procedure. Salivary cortisol levels were analyzed using SLV-4635 (formerly SLV-2930) DRG Instruments GmbH German using the ELISA technique. Statistical analysis was performed using SPSS 22.0. RESULTS: A total of 37 procedures with 74 salivary cortisol samples and 259 questionnaire responses from S were analyzed. All patients with only benign FNAC were operated upon (64.9% colloid). Mean TSH levels were 3.5 ± 6.7 mIU/L. The majority had a solitary thyroid nodule (STN) (25/37, 67.6%). Nineteen patients (51.3%) underwent open hemithyroidectomy, 10 patients total thyroidectomy, and eight patients endoscopic hemithyroidectomy. The mean noise level in the OR was 70 db. The maximum and minimum noise level in the OR was 90.06 and 51.81 dB, respectively. A total of 74 salivary cortisol samples from the S were collected (baseline and post-noise exposure) and mean cortisol levels were recorded. The surgeon was more significantly affected by surrounding noise, especially during critical phases 3 of surgery, mainly, RLN dissection and parathyroid dissection as recorded by their responses in the questionnaire (p = 0.003). The maximum value of post-operative salivary cortisol of surgeon was recorded as 23. 48 ng/mL and the minimum value recorded was 0.49 ng/mL. The difference in baseline cortisol and post-noise exposure cortisol levels of surgeon was found to be significant (p < 0.001). Maximum and mean noise levels were significantly associated with post-noise exposure salivary cortisol elevation in the surgeon (p = 0.032 and 0.014, respectively). The noise levels during RLN dissection were borderline significant with the post-noise exposure salivary cortisol of the surgeon (p = 0.055). CONCLUSION: Our research is the first such study which has been done to assess noise levels and their effect on thyroidectomy using objective salivary cortisol measurement. It challenges the misconstrued notion that visceral surgeries requiring lesser instruments are not associated with noise-related stress. Noise is a major distraction and the effect of long-term effect on the entire surgical team needs to be studied.


Subject(s)
Surgeons , Thyroid Nodule , Humans , Thyroidectomy/adverse effects , Thyroidectomy/methods , Operating Rooms , Hydrocortisone/analysis , Thyroid Nodule/surgery
16.
J Pharm Biomed Anal ; 239: 115920, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38113826

ABSTRACT

Unforeseen surfacing of microbial keratitis (MKT) over the years has led to a requisite for promising treatment strategy involving combination of antifungal and antibacterial agents. Subsequently, symptoms associated with MKT including inflammation and watery eyes require treatment with anti-inflammatory agents. Thus, a requirement of functional clinical treatment strategy involving combination of anti-inflammatory corticosteroids (Betamethasone) with antifungal polyene (Amphotericin B, AmB) and antibacterials macrolide (Azithromycin, AZT) and aminoglycoside (Neomycin, NEO). In the ensuing pursuit, a sensitive and fast simultaneous LC-MS/MS method of four drastically different analytes in rabbit tear fluid and cornea was developed and validated as per US-FDA guidelines. The gradient LC set-up was used with C18 column and flow rate of 0.55 mL/min along with short run time of 7 min. The calibration curves showed good linearity over the concentration range of 0.07-300 ng/mL, 1.00-400 ng/mL, 3.00-600 ng/mL and 8.00-900 ng/mL for AZT, AmB, NEO and BEM respectively. The bioanalytical method requires only 10 µL of ocular sample and analytes were extracted with fast protein precipitation with acidic methanol. Finally, the developed method was validated for selectivity, linearity (r2 > 0.99), precision, accuracy, matrix effects, and stability. PK-PD indices and dosing frequency was predicted using Phoenix WinNonlin Software, based on single dose ocular pharmacokinetics and MIC values of AmB, AZT and NEO. According to the PK-PD simulation, S. aureus and E. coli required 6 and 12 instillations of AZT per 24 h, respectively whereas 12 instillation of NEO requires per 24 h for S. aureus. The result suggests that to minimize antimicrobial resistance; drug, dose and dosing schedule depend upon the pathogen as well as the strain.


Subject(s)
Antifungal Agents , Keratitis , Animals , Rabbits , Antifungal Agents/pharmacokinetics , Chromatography, Liquid/methods , Liquid Chromatography-Mass Spectrometry , Tandem Mass Spectrometry/methods , Staphylococcus aureus , Escherichia coli , Anti-Bacterial Agents/pharmacology , Cornea , Anti-Inflammatory Agents , Keratitis/drug therapy , Reproducibility of Results
17.
Xenobiotica ; 53(6-7): 484-497, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37787761

ABSTRACT

1. The current investigation was to develop and validate the LC-MS/MS method in order to analyse the various pharmacokinetic parameters of S019-0385. A sensitive, selective, and robust LC-MS/MS approach was established and validated for measuring S019-0385 in female mice plasma and tissue, using optimal multiple reaction monitoring (MRM) transition m/z 488.25/329.12 on positive mode. On a Waters Symmetry Shield C18 column, the analyte was separated using acetonitrile and deionised water with formic acid within 6 min at 0.7 mL/min. Linearity (R2 ≥ 0.99) was observed across 0.195-100 ng/mL concentration range using linear least-squares regression.2. Blood-to-plasma ratio and plasma protein drug binding (%) in mice and human was assessed and found to be less than 1 and >83%, respectively. Absolute bioavailability (%F) of S019-0385 in female Swiss mice was exhibited to be 6.90%. Percent dose excreted S019-0385 in unchanged form through urine and faecal was found to be less than 2% and 0.5%, respectively.3. Following oral administration at 5 mg/kg, the concentration of S019-0385 in tissue distribution was found to be in the order of C small intestine > C bone > C lung > C spleen > C kidney > C liver > C heart > C brain.


Subject(s)
Tandem Mass Spectrometry , Humans , Mice , Female , Animals , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Tissue Distribution , Biological Availability , Feces , Reproducibility of Results
18.
AAPS PharmSciTech ; 24(8): 217, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37891392

ABSTRACT

The eye, an intricate organ comprising physical and physiological barriers, poses a significant challenge for ophthalmic physicians seeking to treat serious ocular diseases affecting the posterior segment, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Despite extensive efforts, the delivery of therapeutic drugs to the rear part of the eye remains an unresolved issue. This comprehensive review delves into conventional and innovative formulation strategies for drug delivery to the posterior segment of the eye. By utilizing alternative nanoformulation approaches such as liposomes, nanoparticles, and microneedle patches, researchers and clinicians can overcome the limitations of conventional eye drops and achieve more effective drug delivery to the posterior segment of the eye. These innovative strategies offer improved drug penetration, prolonged residence time, and controlled release, enhancing therapeutic outcomes for ocular diseases. Moreover, this article explores recently approved delivery systems that leverage diverse polymer technologies, such as chitosan and hyaluronic acid, to regulate drug-controlled release over an extended period. By offering a comprehensive understanding of the available formulation strategies, this review aims to empower researchers and clinicians in their pursuit of developing highly effective treatments for posterior-segment ocular diseases.


Subject(s)
Eye Diseases , Macular Degeneration , Humans , Delayed-Action Preparations/therapeutic use , Eye , Drug Delivery Systems , Liposomes/therapeutic use , Macular Degeneration/drug therapy , Eye Diseases/drug therapy
20.
Ann Med Surg (Lond) ; 85(9): 4228-4233, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37663692

ABSTRACT

Background: Breast self-examination (BSE) plays an important role in the early diagnosis of breast cancer in India owing to the stigma attached to cancer. The authors compared the efficacies of animation video versus simulation techniques in BSE. Methods: Women with no previous history of conditions affecting the breasts were included in this prospective observational study and divided into an animation or simulation arm. The latter was further divided into three subgroups as per the simulation models used : the German (Delta Healthcare), British (Health Edco), and Indian (low-cost, validated) models used for teaching BSE. The hybrid animation video had a 9 min runtime with a lecture on BSE and a virtual character performing BSE. In both the arms, participants filled in a validated modified patient satisfaction questionnaire. Results: A total of 500 women participated. The mean age of the participants in the animation video arm was 20.21±3.88 years and 19.34±2.27, 22.94±9.6, and 18.97±1.31(20.41±5.99) years in the Indian, German, and British simulation models arm, respectively. The age difference between the two arms was statistically significant (P<0.05). Both animation video and simulation models were found to be useful by the participants. The participants' response to animation video being a better organized tool for learning BSE was statistically significant (90.48±7.98 vs. 84.02±15.09 P≤0.001) when compared to simulation models. The younger women (≤20 years) found these tools significantly more useful than those aged >20 years. Conclusions: All models had good efficiency and utility as learning tools for BSE. However, large studies in BSE set up with combination models are needed.

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