Efficacy of Tamsulosin, Oxybutynin, and their combination in the control of double-j stent-related lower urinary tract symptoms

ABSTRACT Introduction and objective Indwelling double J ureteral stents are used routinely in the resolution of ureteral obstruction caused by different etiologies. Evaluation of urinary symptoms related to double-J stent, indicate that these affect 73-90% of patients. We conducted a prospective, randomized study, to evaluate the efficacy of tamsulosin, oxybutinin and combination therapy in improving the urinary symptoms. Methods Patients who underwent ureteral stent placement after ureterolithotripsy (total 51), were randomized into three groups: Group I: Tamsulosin 0.4 mg. once per day(17 patients), Group II: Oxybutinin 5 mg. once per day (17 patients), Group III: Tamsulosin+ oxybutynin once per day (17 patients). All the groups received the drugs for three weeks and completed a Spanish validated Ureteral Stent Symptom Questionnaire (USSQ) at day 7 and 21. Results Repeated measures ANOVA showed mean urinary symptom index score was 22.3 vs. 15.5 in group three (p<0.001) at day 7 and 21 respectively. The mean work performance index was 6.6 vs 8.1 (p=0.049) favoring tamsulosin group, the mean sexual score was 0.5 vs 1.5 (p=0.03). Among additional problems the mean was 7.2 vs 6.2 (p=0.03). No significant difference was noted among pain and general health index. No side effects were reported. Conclusions Combination therapy with tamsulosin and oxybutynin improved irritative symptoms and work performance as well as sexual matters. Combination therapy should be considered for patients who complained of stent related symptoms

Pathological Studies and Postmortem Computed Tomography of Dolphins with Meningoencephalomyelitis and Osteoarthritis Caused by Brucella ceti

We thank all the personnel of the Aquatic Animal Virtopsy Lab, Hong Kong and SENASA of Costa Rica, especially to the Central Pacific Region and LANASEVE, Hellen Porras Fernández, Juan Carlos Alvarado, Osvaldo Barrantes Granados, Jacqueline Cubillo Morera, Josimar Estrella Morales, Eunice Viquez Ruiz, and the personnel from Parque Marino del Pacífico for their collaboration with the localization and handling of the stranded animals. Additionally, we want to give a special thanks to Jimmy Vargas Olivares from the Hospital San Vicente de Paul for assisting in the histopathological preparations. We also thank the Municipal Police and Coastguard of Costa Rica, the personnel from the Program of Investigation of Tropical Diseases (PIET) to Nazareth Ruiz Oceans 2022, 3 202 Villalobos, and Karol Roca for their collaboration during necropsies. This work was supported and approved as part of the National Program of Wildlife of SENASA San José, Costa Rica.Cetacean neurobrucellosis is a common cause of strandings in Costa Rica diagnosed by serology, bacteriology, and histopathology. Pathological studies were performed on 18 dolphins. Twelve were scanned by postmortem computed tomography (PMCT) as a complementary tool for describing neurobrucellosis and osteoarticular alterations associated with Brucella ceti infections. The central nervous system (CNS) and the skeleton of five dolphins not infected with B ceti did not reveal alterations by PMCT scanning. Seven Brucella-infected dolphins showed at least bilateral ventriculomegaly associated with hydrocephalus and accumulation in CSF in the lateral ventricles. We performed semiquantitative grading of the inflammatory process in the different areas of the CNS and evaluated the thickness of the cellular infiltrate in the meninges and the perivascular cuffs. The results for the severity grading were graphed to provide an injury profile associated with each area of the CNS. Age is not a decisive factor regarding neurobrucellosis presentation. The severity of ventriculomegaly by PMCT does not directly correlate with the severity of the inflammatory index determined by histopathological parameters of the brain cortex and other CNS regions, suggesting that these processes, although linked, are multifactorial and need further characterization and validation to establish better cutoffs on the PMCT.La neurobrucelosis de los cetáceos es una causa común de varamientos en Costa Rica diagnosticada por serología, bacteriología e histopatología. Se realizaron estudios patológicos en 18 delfines. Doce fueron escaneados mediante tomografía computarizada postmortem (TCPM) como herramienta complementaria para describir la neurobrucelosis y las alteraciones osteoarticulares asociadas a las infecciones por Brucella ceti. El sistema nervioso central (SNC) y el esqueleto de cinco delfines no infectados por B ceti no revelaron no mostraron alteraciones en la TCMP. Siete delfines infectados por Brucella mostraron al menos ventriculomegalia bilateral asociada con hidrocefalia y acumulación de LCR en los ventrículos laterales. Nosotros Se realizó una clasificación semicuantitativa del proceso inflamatorio en las diferentes áreas del SNC y evaluamos el grosor del infiltrado celular en las meninges y en los manguitos perivasculares. Los resultados de Los resultados de la clasificación de la gravedad se graficaron para proporcionar un perfil de lesión asociado a cada área del SNC. La edad no es un factor decisivo en la presentación de la neurobrucelosis. La gravedad de la La gravedad de la ventriculomegalia por PMCT no se correlaciona directamente con la gravedad del índice inflamatorio determinado por los parámetros histopatológicos de la corteza cerebral y otras regiones del SNC, lo que sugiere que estos procesos, aunque vinculados, son multifactoriales y necesitan una mayor caracterización y validación para establecer mejores puntos de corte en la PMCT.Universidad Nacional, Costa RicaEscuela de Medicina Veterinari

Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective

Background: Risk factors for developing long COVID are not clearly established. The present study was designed to determine if any sign, symptom, or treatment of the acute phase, or personal characteristics of the patient, is associated with the development of long COVID. Methods: A cohort study was carried out, randomly selecting symptomatic COVID-19 patients and not vaccinated. The severity of the acute illness was assessed through the number of compatible COVID-19 symptoms, hospitalizations, and the symptom severity score using a 10-point visual analog scale. Results: After multivariate analysis, a severity score ≥8 (RR 2.0, 95%CI 1.1–3.5, p = 0.022), hospitalization (RR 2.1, 95%CI 1.0–4.4, p = 0.039), myalgia (RR 1.9, 95%CI 1.08–3.6, p = 0.027), tachycardia (RR 10.4, 95%CI 2.2–47.7, p = 0.003), and use of antibiotics (RR 2.0, 95%CI 1.1–3.5, p = 0.022), was positively associated with the risk of having long COVID. Higher levels of education (RR 0.6, 95%CI 0.4–0.9, p = 0.029) and type positive B blood group (B + AB, RR 0.44, 95%CI 0.2–0.9, p = 0.044) were protective factors. The most important population attributable fractions (PAFs) for long COVID were myalgia (37%), severity score ≥8 (31%), and use of antibiotics (27%). Conclusions: Further studies in diverse populations over time are needed to expand the knowledge that could lead us to prevent and/or treat long COVID

A phase I–II controlled randomized trial using a promising novel cell-free formulation for articular cartilage regeneration as treatment of severe osteoarthritis of the knee

Abstract Background A promising novel cell-free bioactive formulation for articular cartilage regeneration, called BIOF2, has recently been tested in pre-clinical trials. The aim of the present study was to evaluate the efficacy and safety of BIOF2 for intra-articular application in patients with severe osteoarthritis of the knee. Methods A prospective, randomized, 3-arm, parallel group clinical trial was conducted. It included 24 patients with severe osteoarthritis of the knee (WOMAC score 65.9 ± 17). Before they entered the study, all the patients were under osteoarthritis control through the standard treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed by their family physician. Patients were distributed into three groups of 8 patients each (intra-articular BIOF2, total joint arthroplasty, or conservative treatment with NSAIDs alone). The WOMAC score, RAPID3 score, and Rasmussen clinical score were evaluated before treatment and at months 3, 6, and 12. BIOF2 was applied at months 0, 3, and 6. Complete blood count and blood chemistry parameters were determined in the BIOF2 group before treatment, at 72 h, and at months 1, 3, 6, and 12. In addition, articular cartilage volume was evaluated (according to MRI) at the beginning of the study and at month 12. Results The NSAID group showed no improvement at follow-up. Arthroplasty and BIOF2 treatments showed significant improvement in all the scoring scales starting at month 3. There were no statistically significant differences between the BIOF2 group and the arthroplasty group at month 6 (WOMAC score: 19.3 ± 18 vs 4.3 ± 5; P = 0.24) or month 12 (WOMAC score: 15.6 ± 15 vs 15.7 ± 17; P = 1.0). Arthroplasty and BIOF2 were successful at month 12 (according to a WOMAC score: ≤ 16) in 75% of the patients and the daily use of NSAIDs was reduced, compared with the group treated exclusively with NSAIDs (RR = 0.33, 95% CI 0.12–0.87, P = 0.02. This result was the same for BIOF2 vs NSAIDs and arthroplasty vs NSAIDs). BIOF2 significantly increased the articular cartilage by 22% (26.1 ± 10 vs 31.9 ± 10 cm2, P < 0.001) and produced a significant reduction in serum lipids. BIOF2 was well tolerated, causing slight-to-moderate pain only upon application. Conclusions The intra-articular application of the new bioactive cell-free formulation (BIOF2) was well tolerated and showed no significative differences with arthroplasty for the treatment of severe osteoarthritis of the knee. BIOF2 can regenerate articular cartilage and is an easily implemented alternative therapy for the treatment of osteoarthritis. Trial registration Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000250. Registered 08/15/2017—Retrospectively registered, http://rpcec.sld.cu/en/trials/RPCEC00000250-En

Histological changes caused by meclofenamic acid in androgen independent prostate cancer tumors: evaluation in a mouse model

ABSTRACT Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity. Further studies are needed to evaluate the molecular changes that cause the beneficial and therapeutic effects of meclofenamic acid in androgen-independent prostate cancer

Brucella sp. sequence‑type 27 associated with abortion in dwarf sperm whale Kogia sima

A dwarf sperm whale Kogia sima stranded alive along the Central Pacifc Coast of Costa Rica. The whale, handled by tourists and local inhabitants, was weak, had buoyancy difculties, and eventually aborted and died, showing severe necrotizing placentitis and other pathological signs. Both the mother and the fetus had antibodies against Brucella lipopolysaccharide. Brucella organisms were isolated from various tissues of both animals and were characterized. The bacterium genome corresponded to sequence-type 27 (ST27) and clustered together with other Brucella ST27 isolated in humans and cetaceans.Un cachalote enano Kogia sima varó vivo en la costa del Pacífico Central de Costa Rica. La ballena, manipulada por los turistas y los habitantes de la zona, estaba débil, tenía problemas de flotabilidad y finalmente abortó y murió, mostrando una grave placentitis necrotizante y otros signos patológicos. placentitis y otros signos patológicos. Tanto la madre como el feto tenían anticuerpos contra el lipopolisacárido de Brucella. Se aislaron organismos de Brucella de varios tejidos de ambos animales y se caracterizaron. El genoma de la bacteria correspondía al tipo de secuencia 27 (ST27) y se agrupaba con otras Brucella ST27 aisladas en humanos y cetáceos.Universidad Nacional, Costa RicaEscuela de Medicina Veterinari

Protective Effect of Neutral Electrolyzed Saline on Gentamicin-Induced Nephrotoxicity: Evaluation of Histopathologic Parameters in a Murine Model

Background and Objectives: Gentamicin (GM) is a nephrotoxic aminoglycoside. Neutral electrolyzed saline (SES) is a compound with anti-inflammatory, antioxidant, and immunomodulatory properties. The objective of the present study was to evaluate whether kidney damage by GM can be prevented and/or reversed through the administration of SES. Materials and Methods: The study was carried out as a prospective, single-blind, five-arm, parallel-group, randomized, preclinical trial. The nephrotoxicity model was established in male BALB/c mice by administering GM at a dose of 100 mg/kg/day intraperitoneally for 30 days, concomitantly administering (+) SES or placebo (physiologic saline solution), and then administering SES for another 30 days after the initial 30 days of GM plus SES or placebo. At the end of the test, the mice were euthanized, and renal tissues were evaluated histopathologically. Results: The GM + placebo group showed significant tubular injury, interstitial fibrosis, and increased interstitial infiltrate of inflammatory cells compared with the group without GM. Tubular injury and interstitial fibrosis were lower in the groups that received concomitant GM + SES compared with the GM + placebo group. SES administration for 30 days after the GM administration periods (GM + placebo and GM + SES for 30 days) did not reduce nephrotoxicity. Conclusions: Intraperitoneal administration of SES prevents gentamicin-induced histologic nephrotoxicity when administered concomitantly, but it cannot reverse the damage when administered later

Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10–40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50–90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug