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Clinics (Sao Paulo, Brazil) 2024Despite strong evidences supporting the protective role of exercise against stress-induced repercussions, the literature remains inconclusive regarding metabolic...
INTRODUCTION
Despite strong evidences supporting the protective role of exercise against stress-induced repercussions, the literature remains inconclusive regarding metabolic aspects. Therefore, this study aimed to evaluate the effect of Physical Training (PT) by swimming on the metabolic parameters of rats subjected to restraint stress.
METHODS
Wistar rats (n = 40) were divided into four groups: Control (C), Trained (T), Stressed (S), and Trained/Stressed (TS). The restraint stress protocol involved confining the animals in PVC pipes for 60 minutes/day for 12 weeks. Concurrently, the swimming PT protocol was performed without additional load in entailed sessions of 60 minutes conducted five days a week for the same duration. The following parameters were analyzed: fitness progression assessed by the physical capacity test, body mass, serum level of glucose, triglyceride, cholesterol and corticosterone, as well as glycemic tolerance test, evaluated after glucose administration (2 g/kg, i.p.).
RESULTS
Trained groups (T and TS) exhibited enhanced physical capacity (169 ± 21 and 162 ± 22% increase, respectively) compared to untrained groups (C: 9 ± 5 and S: 11 ± 13% increase). Corticosterone levels were significantly higher in the S group (335 ± 9 nmoL/L) compared to C (141 ± 3 nmoL/L), T (174 ± 3 nmoL/L) and TS (231 ± 7 nmoL/L), which did not differ from each other. There were no significant changes in serum glucose, cholesterol, and triglyceride levels among the groups. However, the glycemic curve after glucose loading revealed increased glycemia in the S group (area under curve 913 ± 30 AU) but the TS group exhibited values (673 ± 12 AU) similar to the groups C (644 ± 10 AU) and T (649 ± 9 AU).
CONCLUSION
Swimming-based training attenuated stress-induced corticosterone release and prevented glucose intolerance in rats, reinforcing the importance of exercise as a potential strategy to mitigate the pathophysiological effects of stress.
Topics: Animals; Rats, Wistar; Physical Conditioning, Animal; Male; Restraint, Physical; Corticosterone; Blood Glucose; Swimming; Stress, Psychological; Cholesterol; Rats; Triglycerides; Time Factors; Glucose Tolerance Test; Random Allocation; Metabolome
PubMed: 38901134
DOI: 10.1016/j.clinsp.2024.100411 -
PloS One 2024Short and long-term sound-induced stress on daily basis can affect the physiology of avian individuals because they are more susceptible to sound stress in an open...
UNLABELLED
Short and long-term sound-induced stress on daily basis can affect the physiology of avian individuals because they are more susceptible to sound stress in an open environment.
OBJECTIVES
An ex-situ study was carried out to determine the impact of noise on physiology and ptilochronology of non-breeding male domesticated quail birds.
METHODOLOGY
During 60-days long trial, male quail birds, aged 5-weeks, weighing (c.100gm) were used. Out of 72 experimental birds, 18 birds were assigned to the Control Group (G1) while remaining 54 birds were divided equally into 3 treatment groups: Road Traffic noise (G2), Military activity noise (G3) and Human Activities noise (G4). Birds were housed in standard-sized separate cages (20 ×45 × 20 cm), every bird was kept apart in separate cage in open laboratory under maintained environmental conditions. Millet seeds and water were provided to all the experimental birds ad libitum. Noise originated from several sources of recorded high-intensity music (1125 Hz/ 90 dB), was administered for 5-6 hours per day. Observations were recorded in the morning and afternoon. The experiment was conducted during the non-breeding season from August to October in triplicate. Blood sampling was done after 60 days.
RESULTS
According to the current study, noise stress significantly (p<0.05) increased the concentrations of creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, uric acid, cholesterol, triglycerides, total protein, and glucose while a decline in the levels of albumin was seen in treatment birds of G3. While in terms of hematology, total white blood cells count (TWBC), total red blood cells count (TRBC), mean cell volume (MCV) & packed cell volume (PCV) concentrations were raised in blood of treatment birds of G3. In terms of hormones, noise stress significantly (p<0.05) increased the serum concentrations of Corticosterone in G3 while a significant (p<0.05) decline was observed in the concentrations of luteinizing hormone (LH), thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH) in the same group. Moreover, fault bar formation in G3 was more prominent than others.
CONCLUSION
Noise stress can significantly affect serology, hematology, hormonal physiology and ptilochronology in quail birds.
Topics: Animals; Male; Noise; Stress, Physiological; Quail; Corticosterone
PubMed: 38900819
DOI: 10.1371/journal.pone.0305091 -
Blood Jun 2024
Houde CA, Khan A, Jacobus SJ, et al. Treatment outcomes and prognostic factors with lenalidomide, bortezomib, and dexamethasone (RVd) alone versus Rvd plus autologous stem cell transplantation (ASCT) in African American (AA) patients (Pts) with newly diagnosed multiple myeloma (NDMM) in the...
Topics: Humans; Multiple Myeloma; Dexamethasone; Lenalidomide; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Transplantation, Autologous; Black or African American; Prognosis; Hematopoietic Stem Cell Transplantation; Treatment Outcome; Male; Female; Middle Aged
PubMed: 38900470
DOI: 10.1182/blood.2024025081 -
Annals of Medicine Dec 2024Microscopic colitis has been increasingly recognized as a cause of chronic diarrhoea. We aimed to characterize the role of disease-related factors and treatments on the...
BACKGROUND AND AIMS
Microscopic colitis has been increasingly recognized as a cause of chronic diarrhoea. We aimed to characterize the role of disease-related factors and treatments on the clinical outcomes of microscopic colitis.
METHODS
We retrospectively reviewed the medical records of patients with microscopic colitis who were treated at the University of Chicago and Oregon Health & Science University between August 2010 and May 2016. Patient characteristics and treatments were evaluated as predictors of clinical outcomes using univariate and multivariate analyses. Clinical remission was defined as no symptoms associated with microscopic colitis based on physician assessment and histologic remission was defined as no evidence of histological inflammation of microscopic colitis.
RESULTS
Seventy-two patients with microscopic colitis were included in the study (28 with lymphocytic colitis and 44 with collagenous colitis). Non-steroidal anti-inflammatory drugs, proton pump inhibitors and selective serotonin reuptake inhibitors were used in 23 (31.9%), 14 (19.4%) and 15 (20.8%), respectively, at the time of diagnosis. Among 46 patients with adequate follow-up data, 25 (54.3%) patients achieved clinical remission. Response to budesonide ( = .0002) and achieving histologic remission ( = .0008) were associated with clinical remission on univariate analysis. On multivariate analysis, budesonide response ( = .0052) was associated with clinical remission (odds ratio 25.00, 95% confidence interval 2.63-238.10). Among 22 patients who underwent a follow-up colonoscopy, five patients (22.7%) achieved histologic remission. All patients with histologic remission maintained clinical remission without medication, whereas only two patients (11.8%) were able to discontinue medical therapy when histologic inflammation was present ( = .0002).
CONCLUSIONS
In the present cohort of patients with microscopic colitis, a favourable response to budesonide was significantly associated with long-term clinical remission, and all patients achieving histological remission were able to maintain clinical remission without further medical therapy. Larger studies are required to confirm these findings.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Aged; Colitis, Microscopic; Budesonide; Treatment Outcome; Adult; Remission Induction; Anti-Inflammatory Agents, Non-Steroidal; Proton Pump Inhibitors; Colitis, Lymphocytic; Colitis, Collagenous; Colonoscopy
PubMed: 38900021
DOI: 10.1080/07853890.2024.2365989 -
Translational Vision Science &... Jun 2024To compare gene expression changes following branch retinal vein occlusion (BRVO) in the pig with and without bevacizumab (BEV) and triamcinolone acetonide (TA).
PURPOSE
To compare gene expression changes following branch retinal vein occlusion (BRVO) in the pig with and without bevacizumab (BEV) and triamcinolone acetonide (TA).
METHODS
Photothrombotic BRVOs were created in both eyes of four groups of nine pigs (2, 6, 10, and 20 days). In each group, six pigs received intravitreal injections of BEV in one eye and TA in the fellow eye, with three pigs serving as untreated BRVO controls. Three untreated pigs served as healthy controls. Expression of mRNA of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), dystrophin (DMD), potassium inwardly rectifying channel subfamily J member 10 protein (Kir4.1, KCNJ10), aquaporin-4 (AQP4), stromal cell-derived factor-1α (CXCL12), interleukin-6 (IL6), interleukin-8 (IL8), monocyte chemoattractant protein-1 (CCL2), intercellular adhesion molecule 1 (ICAM1), and heat shock factor 1 (HSF1) were analyzed by quantitative reverse-transcription polymerase chain reaction. Retinal VEGF protein levels were characterized by immunohistochemistry.
RESULTS
In untreated eyes, BRVO significantly increased expression of GFAP, IL8, CCL2, ICAM1, HSF1, and AQP4. Expression of VEGF, KCNJ10, and CXCL12 was significantly reduced by 6 days post-BRVO, with expression recovering to healthy control levels by day 20. Treatment with BEV or TA significantly increased VEGF, DMD, and IL6 expression compared with untreated BRVO eyes and suppressed BRVO-induced CCL2 and AQP4 upregulation, as well as recovery of KCNJ10 expression, at 10 to 20 days post-BRVO.
CONCLUSIONS
Inflammation and cellular osmohomeostasis rather than VEGF suppression appear to play important roles in BRVO-induced retinal neurodegeneration, enhanced in both BEV- and TA-treated retinas.
TRANSLATIONAL RELEVANCE
Inner retinal neurodegeneration seen in this acute model of BRVO appears to be mediated by inflammation and alterations in osmohomeostasis rather than VEGF inhibition, which may have implications for more specific treatment modalities in the acute phase of BRVO.
Topics: Animals; Bevacizumab; Triamcinolone Acetonide; Retinal Vein Occlusion; Disease Models, Animal; Angiogenesis Inhibitors; Cytokines; Intravitreal Injections; Swine; Vascular Endothelial Growth Factor A; RNA, Messenger; Glucocorticoids; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Potassium Channels, Inwardly Rectifying
PubMed: 38899953
DOI: 10.1167/tvst.13.6.13 -
The New England Journal of Medicine Jun 2024The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but...
BACKGROUND
The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown.
METHODS
We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs. A phase 2 expansion in patients with germinal-center B-cell (GCB) and non-GCB DLBCL was performed. ViPOR was administered every 21 days for six cycles.
RESULTS
In phase 1b of the study, involving 20 patients (10 with DLBCL), a single dose-limiting toxic effect of grade 3 intracranial hemorrhage occurred, a result that established venetoclax at a dose of 800 mg as the recommended phase 2 dose. Phase 2 included 40 patients with DLBCL. Toxic effects that were observed among all the patients included grade 3 or 4 neutropenia (in 24% of the cycles), thrombocytopenia (in 23%), anemia (in 7%), and febrile neutropenia (in 1%). Objective responses occurred in 54% of 48 evaluable patients with DLBCL, and complete responses occurred in 38%; complete responses were exclusively in patients with non-GCB DLBCL and high-grade B-cell lymphoma with rearrangements of and or (or both). Circulating tumor DNA was undetectable in 33% of the patients at the end of ViPOR therapy. With a median follow-up of 40 months, 2-year progression-free survival and overall survival were 34% (95% confidence interval [CI], 21 to 47) and 36% (95% CI, 23 to 49), respectively.
CONCLUSIONS
Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated with mainly reversible adverse events. (Funded by the Intramural Research Program of the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health and others; ClinicalTrials.gov number, NCT03223610.).
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Female; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Sulfonamides; Aged; Male; Bridged Bicyclo Compounds, Heterocyclic; Lenalidomide; Piperidines; Adult; Antibodies, Monoclonal, Humanized; Prednisone; Adenine; Aged, 80 and over; Recurrence; Pyrazoles; Pyrimidines; Molecular Targeted Therapy; Progression-Free Survival
PubMed: 38899693
DOI: 10.1056/NEJMoa2401532 -
Biological & Pharmaceutical Bulletin 2024Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in...
Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.
Topics: Aprepitant; Carboplatin; Humans; Dexamethasone; Palonosetron; Male; Etoposide; Antiemetics; Female; Middle Aged; Vomiting; Aged; Nausea; Retrospective Studies; Adult; Drug Therapy, Combination; Antineoplastic Combined Chemotherapy Protocols; Quinuclidines; Morpholines; Antineoplastic Agents; Isoquinolines; Treatment Outcome
PubMed: 38897969
DOI: 10.1248/bpb.b24-00046 -
Experimental Cell Research Jul 2024Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of...
Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of irreversible vision loss. There are currently no effective treatment strategies for glaucoma. Mitochondrial function plays a crucial role in regulating IOP within the TM. In this study, primary TM cells treated with dexamethasone were used to simulate glaucomatous changes, showing abnormal cellular cytoskeleton, increased expression of extracellular matrix, and disrupted mitochondrial fusion and fission dynamics. Furthermore, glaucomatous TM cell line GTM3 exhibited impaired mitochondrial membrane potential and phagocytic function, accompanied by decreased oxidative respiratory levels as compared to normal TM cells iHTM. Mechanistically, lower NAD + levels in GTM3, possibly associated with increased expression of key enzymes CD38 and PARP1 related to NAD + consumption, were observed. Supplementation of NAD + restored mitochondrial function and cellular viability in GTM3 cells. Therefore, we propose that the aberrant mitochondrial function in glaucomatous TM cells may be attributed to increased NAD + consumption dependent on CD38 and PARP1, and NAD + supplementation could effectively ameliorate mitochondrial function and improve TM function, providing a novel alternative approach for glaucoma treatment.
Topics: Trabecular Meshwork; Mitochondria; Glaucoma; NAD; Humans; Membrane Potential, Mitochondrial; Intraocular Pressure; Cell Survival; ADP-ribosyl Cyclase 1; Cell Line; Poly (ADP-Ribose) Polymerase-1; Dexamethasone; Cells, Cultured
PubMed: 38897410
DOI: 10.1016/j.yexcr.2024.114137 -
FP Essentials Jun 2024Acne is a chronic, recurrent inflammatory condition of the pilosebaceous unit. It affects approximately 85% of adolescents and creates significant psychosocial and... (Review)
Review
Acne is a chronic, recurrent inflammatory condition of the pilosebaceous unit. It affects approximately 85% of adolescents and creates significant psychosocial and financial burdens. The pathogenesis involves altered follicular growth and differentiation, microbial colonization with , increased sebum production influenced by androgen levels, and inflammation. Evidence-based risk factors include family history and body mass index. Diagnosis of acne is clinical, according to patient age and acne morphology and severity. Setting treatment expectations is an important aspect of management. For mild acne, benzoyl peroxide is an effective first-line drug as monotherapy or in combination with a topical retinoid and/or topical antibiotic. Oral tetracyclines are first-line drugs as part of a multipart treatment regimen for moderate to severe acne for patients older than 8 years. Oral isotretinoin is the first-line drug for moderate to severe inflammatory acne. Because of its teratogenic effects, its prescribing is monitored through the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) program. Prescribing oral or topical antibiotics as monotherapy for acne is not recommended, as this may increase microbial resistance. Combined oral contraceptives and spironolactone are used as adjunctive therapies in female adolescents. Patients with skin of color, pregnant patients, and transgender or gender diverse patients warrant special considerations in acne management.
Topics: Humans; Acne Vulgaris; Adolescent; Child; Dermatologic Agents; Anti-Bacterial Agents; Isotretinoin; Female; Benzoyl Peroxide; Risk Factors; Male; Spironolactone; Retinoids
PubMed: 38896825
DOI: No ID Found -
Reproduction in Domestic Animals =... Jun 2024This study evaluated the effect of bovine somatotropin (bST) on pregnancy rate (PR) and size of the dominant follicle (DF) on the day of intravaginal progesterone (P4)...
This study evaluated the effect of bovine somatotropin (bST) on pregnancy rate (PR) and size of the dominant follicle (DF) on the day of intravaginal progesterone (P4) removal in protocols for fixed-time artificial insemination (FTAI). Bos indicus (Nellore) females (n = 392) were distributed into three groups. The control group (CG; n = 92) received an intravaginal P4 device + estradiol benzoate on day (d)0; prostaglandin F2α on d7 (first application); removal of P4 + estradiol cypionate (EC) + PGF2α (second application) + ultrasound (US) of the DF on d9; the FTAI was performed on d11; and pregnancy diagnosis (PD) was performed on d45. The bST group (bSTG; n = 142) underwent the same protocol as the CG, except that the animals received 125 mg of bST on d7. The equine chorionic gonadotropin (eCG) group (eCGG; n = 158) underwent the same protocol as the CG, except that the animals received 300 IU of eCG on d9. The PRs of the bSTG, eCGG, and CG were 48%, 48%, and 35%, respectively (p < .05); the bSTG and eCGG showed greater PRs, with follicles 6-7.9 mm (p < .05) and 8-8.9 mm in diameter, respectively. The bSTG exhibited a greater dimension of the DF on d9 of the protocol (p < .05). The eCGG had higher PRs with a body condition score (BCS) of 2.5, and the bSTG had a BCS of 3.0 (p < .05). It was concluded that bST increased PR, bST showed better performance in smaller DF and larger follicular diameter on d9 of the protocol, eCG acted better on animals with lower BCSs, and bST can be used in FTAI.
Topics: Animals; Female; Insemination, Artificial; Pregnancy; Cattle; Growth Hormone; Progesterone; Pregnancy Rate; Estradiol; Ovarian Follicle; Dinoprost; Estrus Synchronization; Administration, Intravaginal
PubMed: 38894646
DOI: 10.1111/rda.14642