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Frontiers in Bioscience (Scholar... Dec 2023Diarrhea is the increase in the excretion of human water; meanwhile, fisetin, a bioactive flavonol molecule, is widely used in the treatment/prevention of...
BACKGROUND
Diarrhea is the increase in the excretion of human water; meanwhile, fisetin, a bioactive flavonol molecule, is widely used in the treatment/prevention of gastrointestinal disorders. The purpose of this study is to investigate the anti-diarrheal activity of fisetin by restoring kidney function, antioxidant activity, inflammatory markers, Na+/K+-ATPase level, apoptosis, and protein content in diarrheal rats.
METHODS
A total of 36 male rats were distributed into two groups (18 rats/group): normal and diarrheal. The normal group was further divided into three subgroups (6 rats/subgroup): Control, fisetin, and desmopressin drug subgroups, consisting of normal rats orally treated once a day for 4 weeks with 1 mL distilled water, 50 mg/kg fisetin, and 1 mg/kg desmopressin drug, respectively. A lactose diet containing 35% lactose was fed to the normal rats for a month. The diarrheal rats were also divided into three subgroups (6 rats/subgroup): diarrheal rats, diarrheal rats + fisetin, and diarrheal rats + desmopressin drug groups, whereby the diarrheal rats were orally treated once a day for 4 weeks with 1 mL distilled water, 50 mg/kg fisetin, and 1 mg/kg desmopressin drug, respectively.
RESULTS
Fisetin significantly decreased serum urea (41.20 ± 2.6-29.74 ± 2.65), creatinine (1.43 ± 0.05-0.79 ± 0.06), and urinary volume (1.30 ± 0.41-0.98 ± 0.20), while significantly increasing kidney weight (0.48 ± 0.03-0.67 ± 0.07), sodium, potassium, and chloride balance in both serum and urine. Fisetin significantly increased the antioxidant activity (superoxide dismutase (1170 ± 40-3230 ± 50), glutathione peroxidase (365 ± 18-775 ± 16), catalase (0.09 ± 0.03-0.14 ± 0.06), and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity (8.6 ± 1.31-10.5 ± 1.25), while significantly decreasing malondialdehyde (19.38 ± 0.54-9.54 ± 0.83), conjugated dienes (1.86 ± 0.24-1.64 ± 0.19), and oxidative index (0.62 ± 0.04-0.54 ± 0.05)), alongside the inflammatory markers (tumor necrosis factor-α (65.2 ± 2.59-45.3 ± 2.64), interleukin-1β, interleukin-6 (107 ± 4.5-56.1 ± 7.2), and interleukin-10) in the diarrheal rats to values approaching the control values. Fisetin also restored the Na+/K+-ATPase level, apoptosis, protein content, and kidney architecture in diarrheal rats to be near the control group.
CONCLUSIONS
Fisetin treated diarrhea in rats by restoring kidney function, antioxidant activity, inflammatory markers, apoptosis, proteome content, and histology.
Topics: Humans; Rats; Male; Animals; Antioxidants; Deamino Arginine Vasopressin; Lactose; Rats, Sprague-Dawley; Kidney; Oxidative Stress; Flavonols; Inflammation; Apoptosis; Diarrhea; Adenosine Triphosphatases; Water
PubMed: 38163954
DOI: 10.31083/j.fbs1504014 -
Electrolyte & Blood Pressure : E & BP Dec 2023Hyponatremia is a common electrolyte disorder requiring careful management to prevent severe complications. Osmotic demyelination syndrome (ODS) is a serious...
Hyponatremia is a common electrolyte disorder requiring careful management to prevent severe complications. Osmotic demyelination syndrome (ODS) is a serious neurological disorder that can develop from rapid correction of hyponatremia. Herein, is a description of the case of a 61-year-old man with multiple risk factors, including alcoholism, hypokalemia, malnutrition, and alcoholic liver cirrhosis, who developed ODS despite adherence to the recommended correction rate for hyponatremia. The patient presented to the emergency department with generalized weakness, gait disturbance, and decreased muscle strength. Initial laboratory investigations revealed severe hyponatremia, hypokalemia, and dehydration. The patient was treated with cautious correction of the hyponatremia below 8 mmol/L per day. However, on the seventh hospital day, he developed tremors, rigidity, and decreased consciousness and was diagnosed with osmotic demyelination syndrome. Despite receiving general supportive care, desmopressin, and dextrose 5% in water to reduce the serum sodium levels, the patient did not show significant improvement and was transferred to a nursing home for long-term conservative care on day 35 of hospitalization. This case report highlights the challenges associated with the diagnosis and management of osmotic demyelination syndrome and the importance of identifying patients at high risk of developing this neurological disorder.
PubMed: 38152601
DOI: 10.5049/EBP.2023.21.2.61 -
Blood Apr 2024There is significant ongoing debate regarding type 1 von Willebrand disease (VWD) defintion. Previous guidelines recommended patients with von Willebrand factor (VWF)...
There is significant ongoing debate regarding type 1 von Willebrand disease (VWD) defintion. Previous guidelines recommended patients with von Willebrand factor (VWF) levels <30 IU/dL be diagnosed type 1 VWD, whereas patients with significant bleeding and VWF levels from 30 to 50 IU/dL be diagnosed with low VWF. To elucidate the relationship between type 1 VWD and low VWF in the context of age-induced increases in VWF levels, we combined data sets from 2 national cohort studies: 162 patients with low VWF from the Low VWF in Ireland Cohort (LoVIC) and 403 patients with type 1 VWD from the Willebrand in The Netherlands (WiN) studies. In 47% of type 1 VWD participants, VWF levels remained <30 IU/dL despite increasing age. Conversely, VWF levels increased to the low VWF range (30-50 IU/dL) in 30% and normalized (>50 IU/dL) in 23% of type 1 VWD cases. Crucially, absolute VWF antigen (VWF:Ag) levels and increase of VWF:Ag per year overlapped between low VWF and normalized type 1 VWD participants. Moreover, multiple regression analysis demonstrated that VWF:Ag levels in low VWF and normalized type 1 VWD patients would not have been different had they been diagnosed at the same age (β = 0.00; 95% confidence interval, -0.03 to 0.04). Consistently, no difference was found in the prevalence of VWF sequence variants; factor VIII activity/VWF:Ag or VWF propeptide/VWF:Ag ratios; or desmopressin responses between low VWF and normalized type 1 VWD patients. In conclusion, our findings demonstrate that low VWF does not constitute a discrete clinical or pathological entity. Rather, it is part of an age-dependent type 1 VWD evolving phenotype. Collectively, these data have important implications for future VWD classification criteria.
Topics: Humans; von Willebrand Factor; von Willebrand Disease, Type 1; Netherlands; von Willebrand Diseases; Hemorrhage
PubMed: 38142407
DOI: 10.1182/blood.2023022457 -
Reviews in Endocrine & Metabolic... Jun 2024Arginine vasopressin deficiency (AVP-D) is one of the main entities of the polyuria-polydipsia syndrome. Its correct diagnosis and differentiation from the other two... (Review)
Review
Arginine vasopressin deficiency (AVP-D) is one of the main entities of the polyuria-polydipsia syndrome. Its correct diagnosis and differentiation from the other two causes - AVP resistance and primary polydipsia - is crucial as this determines the further management of these patients.Over the last years, several new diagnostic tests using copeptin, the stable surrogate marker of AVP, have been introduced. Among them, hypertonic saline stimulated copeptin was confirmed to reliably and safely improve the diagnostic accuracy to diagnose AVP-D. Due to its simplicity, arginine stimulated copeptin was put forward as alternative test procedure. Glucagon-stimulated copeptin also showed promising results, while the oral growth hormone secretagogue Macimorelin failed to provide a sufficient stimulus. Interestingly, an approach using machine learning techniques also showed promising results concerning diagnostic accuracy.Once AVP-D is diagnosed, further workup is needed to evaluate its etiology. This will partly define the further treatment and management. In general, treatment of AVP-D focuses on desmopressin substitution, with oral formulations currently showing the best tolerance and safety profile. However, in addition to desmopressin substitution, recent data also showed that psychopathological factors play an important role in managing AVP-D patients.
Topics: Humans; Arginine Vasopressin; Polyuria; Polydipsia; Deamino Arginine Vasopressin; Glycopeptides
PubMed: 38087160
DOI: 10.1007/s11154-023-09862-w -
Urology Annals 2023The purpose of the study is to identify early serum sodium changes that could happen in elderly patients with nocturia receiving desmopressin.
PURPOSE
The purpose of the study is to identify early serum sodium changes that could happen in elderly patients with nocturia receiving desmopressin.
MATERIALS AND METHODS
This study was conducted on 28 patients complaining of nocturia and receiving desmopressin. Inclusion criteria were patients diagnosed as having nocturia (at least one or more voids per night) aging ≥55 years with normal baseline serum sodium (135-150 mEq/L). All patients received desmopressin in the form of 60 μg at bedtime. Close follow-up was done for any adverse effects that may have occurred related to hyponatremia and serum sodium was reevaluated for all patients at 3, 7, 14, and 30 days from the start of the treatment.
RESULTS
Desmopressin resulted in a significant decrease in nocturnal urine volume, a decrease in nocturnal polyuria index, number of night voids and the time to first void was delayed. Furthermore, statistically insignificant sodium drop in males and statistically significant sodium drop in females were noted with infrequent side effects, for example, headache (10.7%) and hyponatremia (7.14%) that started after treatment by 1 week.
CONCLUSION
Hyponatremia can be avoided using the minimal effective dose of desmopressin. To receive desmopressin in elderly patients sodium baseline level must be ≥135 mmol/L. Close sodium monitoring has to be done at 7, 14, and 30 days from start of treatment for high-risk patients (especially elderly) or patients receiving other medication causing hyponatremia.
PubMed: 38074185
DOI: 10.4103/ua.ua_61_22 -
International Journal of Molecular... Nov 2023In cancer patients, hyponatremia is detected in about 40% of cases at hospital admission and has been associated to a worse outcome. We have previously observed that...
In cancer patients, hyponatremia is detected in about 40% of cases at hospital admission and has been associated to a worse outcome. We have previously observed that cancer cells from different tissues show a significantly increased proliferation rate and invasion potential, when cultured in low extracellular [Na]. We have recently developed an animal model of hyponatremia using Foxn1nu/nu mice. The aim of the present study was to compare tumor growth and invasivity of the neuroblastoma cell line SK-N-AS in hyponatremic vs. normonatremic mice. Animals were subcutaneously implanted with luciferase-expressing SK-N-AS cells. When masses reached about 100 mm, hyponatremia was induced in a subgroup of animals via desmopressin infusion. Tumor masses were significantly greater in hyponatremic mice, starting from day 14 and until the day of sacrifice (day 28). Immunohistochemical analysis showed a more intense vascularization and higher levels of expression of the proliferating cell nuclear antigen, chromogranin A and heme oxigenase-1 gene in hyponatremic mice. Finally, metalloproteases were also more abundantly expressed in hyponatremic animals compared to control ones. To our knowledge, this is the first demonstration in an experimental animal model that hyponatremia is associated to increased cancer growth by activating molecular mechanisms that promote proliferation, angiogenesis and invasivity.
Topics: Humans; Mice; Animals; Hyponatremia; Heterografts; Sodium; Neuroblastoma; Hospitalization
PubMed: 38069002
DOI: 10.3390/ijms242316680 -
Acta Bio-medica : Atenei Parmensis Dec 2023Nocturnal enuresis (NE) is a common condition in the pediatric age. NE is defined as an intermittent bedwetting with any frequency while sleeping in children. NE is...
Nocturnal enuresis (NE) is a common condition in the pediatric age. NE is defined as an intermittent bedwetting with any frequency while sleeping in children. NE is classified into primary form (patient never had achieved nocturnal urinary control) or secondary form (children with a period of 6 consecutive months of night-time urinary control before incontinence, which is generally associated with organic or psychological causes). Moreover, NE could be monosymptomatic (MNE) or non-monosymptomatic (NMNE), depending on the presence of daytime incontinence or any other lower urinary tract symptoms (LUTS). We report a 7-year- old female with a history of recent onset of sphincter troubles and recurrent low urinary tract infections. She presented urinary urgency associated to daytime incontinence, bedwetting almost every night in the previous 3 months and sometimes encopresis. The physical and neurological examination was silent, no psychological or social problem intercurred. As first approach, she was treated with deamino-delta-D-arginine vasopressin (dDAVP) 120 mcg associated with oxybutynin 5 mg and educational therapy, for 3 months without benefits. So, she underwent a magnetic resonance imaging (MRI) of the spinal cord, that highlighted the presence of hydrosyringomyelia from D6 to D10, lipoma of the terminal filum and the presence of synovial cyst between L5-S1. This case remarks that in secondary NMNE, any possible organic cause must be investigated.
Topics: Child; Humans; Female; Nocturnal Enuresis; Physical Examination
PubMed: 38054679
DOI: 10.23750/abm.v94i6.14931 -
Frontiers in Endocrinology 2023Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life...
OBJECTIVE
Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively.
METHODS
Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate.
RESULTS
The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%.
CONCLUSION
This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.
Topics: Humans; Child; Craniopharyngioma; Retrospective Studies; Thyroxine; Quality of Life; Deamino Arginine Vasopressin; Neoplasm Recurrence, Local; Pituitary Neoplasms; Hypothalamic Diseases; Pituitary Diseases; Hormone Replacement Therapy; Hydrocortisone
PubMed: 38027203
DOI: 10.3389/fendo.2023.1241145 -
World Journal of Oncology Dec 2023Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Despite being an essential component of systemic chemotherapy for advanced CRC,...
BACKGROUND
Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Despite being an essential component of systemic chemotherapy for advanced CRC, 5-fluorouracil (5-FU) clinical use has severe limitations, such as high toxicity, low selectivity and drug resistance. [VQ]dDAVP (1-deamino-4-valine-5-glutamine-8-D-arginine vasopressin) is a peptide vasopressin analog and a selective agonist of the arginine vasopressin type 2 membrane receptor (AVPR2), expressed in microvascular and tumor tissue. This synthetic compound has well-proven antitumor and antimetastatic activity in different tumor types, including metastatic CRC. The objective of this work was to assess the potential combinational benefits in preclinical CRC models after [VQ]dDAVP addition to 5-FU.
METHODS
Effects on cellular viability, cell cycle progression, apoptosis and molecular mechanisms associated to [VQ]dDAVP treatment in combination with 5-FU were evaluated in murine CT-26 and human COLO-205 cell lines. , impact of dual therapy was explored on CRC tumor growth and metastatic spread.
RESULTS
In CRC cells, [VQ]dDAVP (1 µM) addition to sub-IC 5-FU concentrations resulted in the enhancement of cytostatic effects induced by chemotherapy. Reduction of cell viability after combined treatment was associated with cell cycle arrest in the G/G phase, induction of apoptosis and increased gene expression of the cyclin-dependent kinase inhibitor p21 (CDKN1A) and the tumor suppressor p53 (TP53) in malignant cells, as assessed by flow cytometry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. , intravenous administration of [VQ]dDAVP (0.3 µg/kg) in combination with safe low doses of 5-FU (50 or 80 mg/kg for CT-26 or COLO-205 tumor models, respectively) effectively abrogated CRC growth, reducing aggressiveness of primary lesions and increasing survival of tumor-bearing mice. In addition, concomitant administration of [VQ]dDAVP and 5-FU inhibited pulmonary metastasis formation by CT-26 cells in immunocompetent mice, especially reducing macrometastatic disease.
CONCLUSIONS
[VQ]dDAVP seems to enhance the efficacy of 5-FU-based chemotherapy in CRC by modulating tumor progression, as well as metastatic dissemination, suggesting its potential role as a safe and cost-effective co-adjuvant agent for the management of advanced CRC.
PubMed: 38022396
DOI: 10.14740/wjon1715