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CMAJ : Canadian Medical Association... Jun 2024
Review
Topics: Humans; Food Hypersensitivity; Infant; Child, Preschool; Administration, Oral; Desensitization, Immunologic; Allergens
PubMed: 38885980
DOI: 10.1503/cmaj.231478 -
PloS One 2024Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic...
Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1β, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1β with the regulation of gut microbiota-involved NF-κB signaling.
Topics: Animals; Matrix Metalloproteinase 9; Dry Eye Syndromes; Gastrointestinal Microbiome; Mice; NF-kappa B; Probiotics; Signal Transduction; Mice, Inbred C57BL; Tears; Fecal Microbiota Transplantation; Tumor Necrosis Factor-alpha; Conjunctiva
PubMed: 38885258
DOI: 10.1371/journal.pone.0303423 -
JAMA Network Open Jun 2024Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized...
IMPORTANCE
Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized in clinical practice, especially in Asian countries. One strategy for the early prescription of LAIs is to administer the drugs during patients' first admission, when they have more time to absorb medication-related knowledge.
OBJECTIVE
To estimate the prevalence of and risk factors for in-hospital use of LAIs among first-admission patients with schizophrenia in Taiwan and to examine the association of early discontinuation with readmission risk among patients receiving LAIs.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included data from a claims database for patients with a first admission for schizophrenia at psychiatric wards in Taiwan from 2004 to 2017. Eligible patients were diagnosed with schizophrenia or schizoaffective disorder at discharge and aged between 15 and 64 years. Data analysis was performed from April to September 2022.
EXPOSURE
In-hospital use of LAIs with or without early discontinuation.
MAIN OUTCOME AND MEASURES
Readmission for any psychotic disorder following discharge from first admission, with risk estimated via multivariable survival regression analysis, including the Cox proportional hazards (CPH) model and accelerated failure time (AFT) model.
RESULTS
Of the 56 211 patients with a first admission for schizophrenia (mean [SD] age, 38.1 [12.1] years; 29 387 men [52.3%]), 46 875 (83.4%) did not receive any LAIs during admission, 5665 (10.1%) received LAIs with early discontinuation, and 3671 (6.5%) received LAIs without early discontinuation. The prevalence of receiving LAIs increased by 4%, from 15.3% (3863 of 25 251 patients) to 19.3% (3013 of 15 608 patients) between 2004-2008 and 2013-2017. After controlling for sex, year, prior antipsychotic use, age at first admission, and length of stay, the CPH regression analysis revealed that the readmission risk increased among patients receiving LAIs with early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30) but decreased among patients receiving LAIs without early discontinuation (aHR, 0.88; 95% CI, 0.84-0.92) compared with patients not receiving LAIs. Results remained similar for the AFT model.
CONCLUSIONS AND RELEVANCE
The incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low. In this study, early discontinuation of LAIs was associated with readmission risk-specifically, early discontinuation with a higher risk while the lack of early discontinuation with a lower risk compared with treatment with oral antipsychotics alone-which suggests our results have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia.
Topics: Humans; Schizophrenia; Antipsychotic Agents; Patient Readmission; Male; Taiwan; Female; Adult; Middle Aged; Delayed-Action Preparations; Risk Factors; Adolescent; Young Adult; Cohort Studies; Medication Adherence; Hospitalization; Injections; Proportional Hazards Models
PubMed: 38884998
DOI: 10.1001/jamanetworkopen.2024.17006 -
Journal of Veterinary Internal Medicine Jun 2024Options for treatment of diabetes mellitus in cats are limited to insulin injections and monitoring for hypoglycemia.
Efficacy and safety of once daily oral administration of sodium-glucose cotransporter-2 inhibitor velagliflozin compared with twice daily insulin injection in diabetic cats.
BACKGROUND
Options for treatment of diabetes mellitus in cats are limited to insulin injections and monitoring for hypoglycemia.
HYPOTHESIS
Once daily sodium-glucose cotransporter-2 inhibitor velagliflozin PO is noninferior to insulin injections.
ANIMALS
Client-owned diabetic cats (127 safety; 116 efficacy assessment).
METHODS
Prospective, randomized (1 mg/kg velagliflozin), positive controlled (titrated Caninsulin), open label, noninferiority field trial, comparing number of cats with treatment success in ≥1 clinical variable and ≥1 glycemic variable (margin Δ: 15%) on Day 45; secondary endpoints included glycemic and clinical assessments during 91 days.
RESULTS
On Day 45, 29/54 (54%) velagliflozin-treated cats and 26/62 (42%) Caninsulin-treated cats showed treatment success, demonstrating noninferiority (difference -11.8%; upper 1-sided 97.5% confidence interval, -∞ to 6.3%). By Day 91, quality of life (QoL), polyuria, and polydipsia had improved in 81%, 54% and 61% (velagliflozin); on blood glucose (BG) curves, mean BG was <252 mg/dL in 42/54 (78%; velagliflozin) and 37/62 (60%; Caninsulin); minimum BG was <162 mg/dL in 41/54 (76%; velagliflozin) and 41/62 (66%; Caninsulin); serum fructosamine was <450 μmol/L in 41/54 (76%; velagliflozin) and 38/62 (61%; Caninsulin). Velagliflozin's most frequent adverse events were loose feces/diarrhea (n = 23/61, 38%), positive urine culture (n = 19/61, 31%), and nonclinical hypoglycemia (BG <63 mg/dL; n = 8/61, 13%); Caninsulin's: clinical and nonclinical hypoglycemia (n = 35/66, 53%), positive urine culture (n = 18/66, 27%), and loose feces/diarrhea (n = 10/66, 15%). Diabetic ketoacidosis occurred in 4/61 (7%; velagliflozin) and 0/66 (Caninsulin).
CONCLUSIONS AND CLINICAL IMPORTANCE
Once daily oral administration of velagliflozin was noninferior to insulin injections, showed good QoL and glycemia without clinical hypoglycemia.
PubMed: 38884190
DOI: 10.1111/jvim.17124 -
BioMed Research International 2024PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2...
INTRODUCTION
PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice.
METHODS
Healthy adult male BALB/c mice were randomly divided into three equal groups ( = 10 in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 l saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of , , , , , , , and were measured by RT-PCR.
RESULT
The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in , , and mRNA expression. There were no differences in -cell numbers between groups.
CONCLUSION
Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of , , and in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced mRNA expression and its association with pancreatic cancer risk should be investigated.
Topics: Animals; Omeprazole; Gastrins; Male; Mice; Homeostasis; Mice, Inbred BALB C; Blood Glucose; Insulin Resistance; Insulin; Gene Expression Regulation; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Proton Pump Inhibitors; Glucose
PubMed: 38884019
DOI: 10.1155/2024/7747599 -
Vascular Health and Risk Management 2024Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the... (Review)
Review
Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the literature remains limited. We reported about a 1-year-old boy diagnosed with superficial KHE who received oral propranolol in combination with topical sirolimus and reviewed relevant reports and treatment of superficial KHE.
Topics: Humans; Male; Propranolol; Sarcoma, Kaposi; Hemangioendothelioma; Sirolimus; Administration, Oral; Treatment Outcome; Kasabach-Merritt Syndrome; Infant; Biopsy
PubMed: 38883398
DOI: 10.2147/VHRM.S461505 -
International Journal of Nanomedicine 2024Rheumatoid Arthritis (RA) involves prolonged inflammation of the synovium, damaging joints and causing stiffness and deformity. Celastrol (Cel), derived from the Chinese...
BACKGROUND
Rheumatoid Arthritis (RA) involves prolonged inflammation of the synovium, damaging joints and causing stiffness and deformity. Celastrol (Cel), derived from the Chinese herbal medicine Hook F, offers immunosuppressive effects for RA treatment but is limited by poor solubility and bioavailability.
PURPOSE
In this study, long-circulating Cel-loaded liposomes (Cel-LPs) were used to increase the pharmacokinetics of Cel, thereby improving drug delivery and efficacy for the treatment of RA.
METHODS
Cel-LPs were prepared and administered orally and intravenously to compare the elimination half-life of drugs and bioavailability of Cel. Cel-LPs were prepared using the lipid thin-layer-hydration-extrusion method. Human rheumatoid arthritis synovial (MH7A) cells were used to investigate the compatibility of Cel-LPs. The pharmacokinetic studies were performed on male Sprague-Dawley (SD) rats.
RESULTS
The Cel-LPs had an average size of 72.20 ± 27.99 nm, a PDI of 0.267, a zeta potential of -31.60 ± 6.81 mV, 78.77 ± 5.69% drug entrapment efficiency and sustained release (5.83 ± 0.42% drug loading). The cytotoxicity test showed that liposomes had excellent biocompatibility and the fluorescence microscope diagram indicated that liposome entrapment increased intracellular accumulation of Rhodamine B by MH7A cells. Furthermore, the results exhibited that Cel-LPs improved the pharmacokinetics of Cel by increasing the elimination half-life (t) to 11.71 hr, mean residence time (MRT) to 7.98 hr and apparent volume of distribution (Vz/F) to 44.63 L/kg in rats, compared to the Cel solution.
CONCLUSION
In this study, liposomes were demonstrated to be effective in optimizing the delivery of Cel, enabling the formulation of Cel-LPs with prolonged blood circulation and sustained release characteristics. This formulation enhanced the intravenous solubility and bioavailability of Cel, developing a foundation for its clinical application in RA and providing insights on poorly soluble drug management.
Topics: Pentacyclic Triterpenes; Animals; Liposomes; Triterpenes; Male; Rats, Sprague-Dawley; Humans; Administration, Intravenous; Rats; Biological Availability; Cell Line; Arthritis, Rheumatoid; Particle Size; Cell Survival; Drug Delivery Systems
PubMed: 38882540
DOI: 10.2147/IJN.S461624 -
Drug Design, Development and Therapy 2024Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of Ultrasound-Guided Thoracic Paravertebral Nerve Block Combined with Perineural or IV Dexmedetomidine on Acute and Chronic Pain After Thoracoscopic Resection of Lung Lesions: A Double-Blind Randomized Trial.
BACKGROUND
Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine.
METHODS
A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 μg·kg (RD Group) or 1.0 μg·kg (RD Group), or intravenous (IV) dexmedetomidine 0.5 μg·kg·h (RD Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery.
RESULTS
(1) For the primary outcome, RD Group and RD Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RD Group, RD Group, and RD Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RD Group, RD Group and RD Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD Group, RD Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD Group showed an increased incidence of drowsiness.
CONCLUSION
Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 μg·kg) may be a more appropriate choice.
CLINICAL TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR2200058982).
Topics: Humans; Dexmedetomidine; Double-Blind Method; Male; Nerve Block; Female; Middle Aged; Chronic Pain; Acute Pain; Pain, Postoperative; Aged; Ultrasonography, Interventional; Thoracoscopy; Lung Neoplasms; Adult; Administration, Intravenous
PubMed: 38882043
DOI: 10.2147/DDDT.S457334 -
Translational Cancer Research May 2024Apigenin is a natural flavonoid compound with proven antitumor activity. However, its precise underlying pharmacological mechanism remains unclear. Oxaliplatin (OXA) is...
BACKGROUND
Apigenin is a natural flavonoid compound with proven antitumor activity. However, its precise underlying pharmacological mechanism remains unclear. Oxaliplatin (OXA) is commonly utilized for cancer treatment as a platinum-based chemotherapy drug. However, the utilization of low-dose OXA carries the risk of inducing epithelial-mesenchymal transition (EMT) in cancer cells and promoting tumor metastasis, thereby giving rise to potential side effects. The purpose of this study is to investigate the synergistic inhibitory effect of apigenin and OXA and its potential mechanism.
METHODS
HSC-3 cells of oral squamous carcinoma cells (OSCCs) were divided into control, apigenin-treated and co-treated groups. A wound healing assay was conducted to assess alterations in cellular motility and migration, an invasion assay was performed to assess invasiveness, and a three-dimensional culture assay was employed to evaluate angiogenic capacity. Cultured cells were utilized for total DNA extraction, followed by reverse transcription. Relative RNA levels were obtained, and quantitative polymerase chain reaction (qPCR) analysis was conducted to assess the efficiency of LINC00857 expression.
RESULTS
The administration of a low dose of OXA promoted the migratory, invasive, and angiogenic capabilities of HSC-3 cells, while also regulating EMT-associated molecular markers to facilitate the process of EMT. The inhibitory impact on OSCC proliferation was enhanced by the synergistic effect of apigenin and OXA. Furthermore, the tumor-promoting effects induced by low-dose OXA were notably suppressed through LINC00857.
CONCLUSIONS
Evidence from this study indicates that apigenin can effectively suppress the metastasis of OSCC cancer cells induced by low-dose OXA through inhibiting the level of LINC00857, suggesting a promising therapeutic strategy.
PubMed: 38881938
DOI: 10.21037/tcr-23-2335 -
Translational Cancer Research May 2024Programmed cell death-1 (PD-1) inhibitors and anti-angiogenic drugs have become a hotspot in research of anti-tumor programs; however, they can also cause some rare...
BACKGROUND
Programmed cell death-1 (PD-1) inhibitors and anti-angiogenic drugs have become a hotspot in research of anti-tumor programs; however, they can also cause some rare drug-related adverse reactions. Immune checkpoint inhibitors (ICIs) cause adverse reactions in the body, collectively known as immune-related adverse events (irAEs). Ocular side effects can occur in both targeted and immunotherapy patients, including dry eye, blurred vision, uveitis, conjunctivitis, retinopathy, or thyroid eye disease. To our knowledge, this is the first case report describing corneal ulcers secondary to dry eye in a patient treated with the combination of PD-1 inhibitor sintilimab and multi-targeted receptor tyrosine kinase inhibitor (TKI) anlotinib.
CASE DESCRIPTION
A 65-year-old woman with non-small cell lung cancer (NSCLC) and bone metastases, without pre-existing ocular conditions, experienced mild dry eye symptoms 1 month following treatment with sintilimab (200 mg q3w) in combination with anlotinib (12 mg q3w). Unrelieved dry eye symptoms occurred after the third cycle of chemotherapy, and she was diagnosed with dry eye syndrome. Subsequently, she received corneal protective lens, sodium hyaluronate eye drops, and prednisone treatment. Her corneal epithelial damage did not improve significantly, and within the following 2 months, her vision decreased in both eyes and progressed to bilateral corneal ulcers. Oral administration of sintilimab and anlotinib was interrupted, and treatments such as corticosteroids, anti-inflammatory drugs, and corneal repair were administered; however, both eyes presented with corneal subepithelial defect and corneal scarring. Due to a shortage of donors, no corneal transplantation surgery could be performed.
CONCLUSIONS
The development of corneal epithelial disorders in patients receiving target therapy and immunotherapy may not be reversed by reducing its dose. Although the condition is controlled with the use of glucocorticoids, some eye side effects cannot be cured. The timely detection and intervention of adverse effects of anti-tumor drugs by oncologists and ophthalmologists is critical for rational prescription. Ophthalmologists should be aware of eye side effects in patients using immunotherapy to ensure appropriate treatment and minimize potential eye complications such as dry eye, conjunctivitis, etc.
PubMed: 38881937
DOI: 10.21037/tcr-23-1952