Clinical Lactation Studies of Neuropsychiatric Medications: Clinical Pharmacology and Labeling Considerations.

The availability of clinical pharmacology and safety data regarding the use of prescription medications in pregnant and lactating individuals has been historically limited, despite significant efforts to improve the quantity and quality of the information in labeling. The Food and Drug Administration's (FDA) Pregnancy and Lactation Labeling Rule took effect on June 30, 2015, and updated information in labeling to more clearly describe available data to assist health care providers in counseling pregnant and lactating individuals. Additionally, the FDA published a revised draft guidance, "Clinical Lactation Studies: Considerations for Study Design," to provide pharmaceutical companies and investigators with information about how and when to conduct lactation studies.

Sinus, middle-ear and mastoid radiological findings of severe acute respiratory syndrome coronavirus-2.

Objective: To assess the incidence of radiological inflammation within the paranasal sinuses, middle ear and mastoid in patients with confirmed severe acute respiratory syndrome coronavirus-2.

Methods: A retrospective cohort study was conducted to examine consecutive adults (aged over 18 years) with coronavirus disease 2019 (confirmed on polymerase chain reaction within 7 days of imaging) who underwent computed tomography of the head between 1 March 2020 and 24 June 2020. Lund-Mackay and mastoid and middle-ear opacification scores were used to categorise the extent of sinus and mastoid opacification on axial and coronal computed tomography images.

Doublecortin-like kinase 1 is a therapeutic target in squamous cell carcinoma.

Doublecortin like kinase 1 (DCLK1) plays a crucial role in several cancers including colon and pancreatic adenocarcinomas. However, its role in squamous cell carcinoma (SCC) remains unknown. To this end, we examined DCLK1 expression in head and neck SCC (HNSCC) and anal SCC (ASCC).

The Role of Biofilms in Chronic Otitis Media-Active Squamosal Disease: An Evaluative Study.

Objectives: To study the presence of biofilms in patients of chronic otitis media (COM)-active squamosal disease and to evaluate the microflora and clinical impact of biofilms.

Methods: A total of 35 patients suffering from COM - active squamosal disease was studied. Cholesteatoma sample was collected at the time of mastoid surgery and the same was used to image for biofilms by scanning electron microscope.

Honokiol Affects Stem Cell Viability by Suppressing Oncogenic YAP1 Function to Inhibit Colon Tumorigenesis.

Honokiol (HNK) is a biphenolic compound that has been used in traditional medicine for treating various ailments, including cancers. In this study, we determined the effect of HNK on colon cancer cells in culture and in a colitis-associated cancer model. HNK treatment inhibited proliferation and colony formation while inducing apoptosis.

Circumferential Subannular Tympanoplasty: Panacea for revision tympanoplasty.

Objective: To evaluate the role of Circumferential Subannular Tympanoplasty [CST] in cases of Revision tympanoplasty.

Methods: A retrospective statistical analysis of data of 81 patients who underwent revision tympanoplasty with CST technique [essentially Type I tympanoplasty] was done. An intact graft at the end of 6 months was regarded as a surgical success.

The role of sinus CT in surgical treatment decisions for chronic rhinosinusitis.

Aims & Objectives: To define a predictive role of Lund Mackay CT scan [LM] score in treatment of chronic rhinosinusitis [CRS] by functional endoscopic sinus surgery [FESS].

Materials & Methods: A prospective study was done on the cited subject in a sample size of 30 patients suffering from CRS failing maximal medical treatment. All the patients underwent FESS under general anaesthesia.

Rhabdomyosarcoma: Nose Presenting As Second Primary with Carcinoma Tongue.

Introduction: Presence of two primary malignancies is rare and occurs in 3-5% of the cancer patients. As per our extensive internet research, this is the only reported case of a synchronous sino-nasal embryonal rhabdomyosarcoma with squamous cell carcinoma-tongue. The case report is important because of the rare diagnosis and the challenge we faced in the diagnosis and treatment of the patient because of the paucity of literature available on management adult rhabdomyosarcoma.

Can Pregnancy Lead to Changes in Hearing Threshold?

Purpose: This study explores the changes in hearing thresholds in pregnancy.

Materials And Methods: A prospective hospital-based observational study was performed with a total of 69 patients in the age-group of 18 to 40 years. Patients underwent hearing assessment twice during the study period.

An ornamental plant targets epigenetic signaling to block cancer stem cell-driven colon carcinogenesis.

Phytochemicals modulate key cellular signaling pathways and have proven anticancer effects. Alcea rosea(AR; Hollyhock) is an ornamental plant with known anti-inflammatory properties. This study explored its role as an anticancer agent.

Crocetinic acid inhibits hedgehog signaling to inhibit pancreatic cancer stem cells.

Pancreatic cancer is the fourth leading cause of cancer deaths in the US and no significant treatment is currently available. Here, we describe the effect of crocetinic acid, which we purified from commercial saffron compound crocetin using high performance liquid chromatography. Crocetinic acid inhibits proliferation of pancreatic cancer cell lines in a dose- and time-dependent manner.

Honokiol affects melanoma cell growth by targeting the AMP-activated protein kinase signaling pathway.

Background: Malignant melanoma is an aggressive form of skin cancer with limited effective therapeutic options. Melanoma research concentrates on maximizing the effect on cancer cells with minimal toxicity to normal cells. AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis and has been shown to control tumor progression regulating the cell cycle, protein synthesis, and cell growth and/or survival.

Molecular expression and functional activity of vitamin C specific transport system (SVCT2) in human breast cancer cells.

The main goal of this study is to investigate the expression of sodium dependent vitamin C transport system (SVCT2). Moreover, this investigation has been carried out to define uptake mechanism and intracellular regulation of ascorbic acid (AA) in human breast cancer cells (MDA-MB231, T47D and ZR-75-1). Uptake of [(14)C] AA was studied in MDA-MB231, T47D and ZR-75-1 cells.

Binary and ternary combinations of anti-HIV protease inhibitors: effect on gene expression and functional activity of CYP3A4 and efflux transporters.

Background: The purpose of this study is to identify the effect of binary and ternary combinations of anti-HIV protease inhibitors (PIs) on the expression of metabolizing enzyme (CYP3A4) and efflux transporters [multidrug resistance-associated protein 2 (MRP2), P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)] in a model intestinal cell line (LS-180).

Methods: LS-180 cells were treated with various combinations of PIs (amprenavir, indinavir, saquinavir and lopinavir), and the mRNA expression levels of metabolizing enzyme and efflux transporters were measured using quantitative reverse transcription polymerase chain reaction. The alteration of gene expression was further correlated to the expression of nuclear hormone receptor PXR.

Bitter melon extracts enhance the activity of chemotherapeutic agents through the modulation of multiple drug resistance.

Recently, we demonstrated that extracts of bitter melon (BME) can be used as a preventive/therapeutic agent in colon cancers. Here, we determined BME effects on anticancer activity and bioavailability of doxorubicin (DOX) in colon cancer cells. BME enhanced the effect of DOX on cell proliferation and sensitized the cells toward DOX upon pretreatment.

Methanolic extracts of bitter melon inhibit colon cancer stem cells by affecting energy homeostasis and autophagy.

Bitter melon fruit is recommended in ancient Indian and Chinese medicine for prevention/treatment of diabetes. However its effects on cancer progression are not well understood. Here, we have determined the efficacy of methanolic extracts of bitter melon on colon cancer stem and progenitor cells.

Influence of overexpression of efflux proteins on the function and gene expression of endogenous peptide transporters in MDR-transfected MDCKII cell lines.

The objective of this study is to delineate whether overexpression of human efflux transporters (P-gp, MRP2, and BCRP) in transfected MDCK cells affect the functional activities, and gene and protein expression of endogenous influx peptide transporter system (PepT). Real-time PCR, immunoblotting, uptake and permeability studies of [(3)H]Gly-Sar were conducted on transfected MDCKII and wild-type cells to investigate functional differences. Cellular [(3)H]Gly-Sar accumulation was significantly lower in transfected MDCKII cell lines compared to wild-type cells.

Design and evaluation of a novel nanoparticulate-based formulation encapsulating a HIP complex of lysozyme.

Formulation development of protein therapeutics using polymeric nanoparticles has found very little success in recent years. Major formulation challenges include rapid denaturation, susceptibility to lose bioactivity in presence of organic solvents and poor encapsulation in polymeric matrix. In the present study, we have prepared hydrophobic ion pairing (HIP) complex of lysozyme, a model protein, using dextran sulfate (DS) as a complexing polymer.

Targeted lipid based drug conjugates: a novel strategy for drug delivery.

A majority of studies involving prodrugs are directed to overcome low bioavailability of the parent drug. The aim of this study is to increase the bioavailability of acyclovir (ACV) by designing a novel prodrug delivery system which is more lipophilic, and at the same time site specific. In this study, a lipid raft has been conjugated to the parent drug molecule to impart lipophilicity.

Transfected MDCK cell line with enhanced expression of CYP3A4 and P-glycoprotein as a model to study their role in drug transport and metabolism.

The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drug of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity.

Differential effect of P-gp and MRP2 on cellular translocation of gemifloxacin.

Fluoroquinolones are broad spectrum antibiotics widely indicated in the treatment of both human and animal diseases. The primary objective of this study was to assess short and long term affinities of gemifloxacin towards efflux transporters (P-gp, MRP2) and nuclear hormone receptor (PXR). Uptake and dose dependent inhibition studies were performed with [(14)C] erythromycin (0.

Effect of short term and chronic administration of Sutherlandia frutescens on pharmacokinetics of nevirapine in rats.

Sutherlandia frutescens (sutherlandia), an African herbal supplement was recommended by the South African Ministry of Health for the treatment of AIDS patients. However, no reports yet exist delineating the effect of sutherlandia on pharmacokinetics of antiretroviral agents. Therefore, this investigation aimed at screening the effects of short term and chronic exposure of sutherlandia on oral bioavailability and pharmacokinetics of nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, in Sprague Dawley rats.

Efflux transporters- and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals.

Multidrug regimens and corresponding drug interactions cause many adverse reactions and treatment failures. Drug efflux transporters: P-gp, MRP, BCRP in conjunction with metabolizing enzymes (CYPs) are major factors in such interactions. Most effective combination antiretrovirals (ARV) therapy includes a PI or a NNRTI or two NRTI.

Interaction of gatifloxacin with efflux transporters: a possible mechanism for drug resistance.

The purpose of the study is to screen the interactions of fourth generation fluoroquinolone-gatifloxacin with efflux pumps, i.e., P-gp, MRP2 and BCRP.