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Pulmonary arterial hypertension (PAH) is a form of precapillary pulmonary hypertension caused by a complex process of endothelial dysfunction and vascular remodeling. If left untreated, this progressive disease presents with symptoms of incapacitating fatigue causing marked loss of quality of life, eventually culminating in right ventricular failure and death. Patient management is complex and based on accurate diagnosis, risk stratification, and treatment initiation, with close monitoring of response and disease progression. Understanding the underlying pathophysiology has enabled the development of multiple drugs directed at different targets in the pathological chain. Vasodilator therapy has been the mainstay approach for the last few years, significantly improving quality of life, functional status, and survival. Recent advances in therapies targeting dysfunctional pathways beyond endothelial dysfunction may address the fundamental processes underlying the disease, raising the prospect of increasingly effective options for this high-risk group of patients with a historically poor prognosis.
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Hamstring muscle injuries are prevalent in sports, presenting substantial hurdles for athletes and teams due to their high recurrence rates and prolonged recovery periods. The biceps femoris (BF) muscle is frequently implicated in these injuries, with notably high recurrence rates, particularly at the distal musculotendinous T-junction (DMTJ), where half of BF reinjuries occur. This paper presents a case study of a 31-year-old female long-distance athlete with a history of DMTJ rupture, shedding light on the intricacies associated with hamstring injuries. The case underscores the challenges in accurately interpreting imaging findings, reinforcing the need for clinical-imaging correlation and exploration of lesion mechanisms to achieve an accurate diagnosis, optimize outcomes, and facilitate a safe return to sport.
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Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist.
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INTRODUCTION: Nusinersen was approved for 5q spinal muscular atrophy (SMA), irrespective of age, SMA type or functional status. Nonetheless, long-term data on adults with milder phenotypes are scarce. We aimed to characterize evolution on motor and respiratory function in our cohort of adults with type 3 SMA. METHODS: We conducted a longitudinal retrospective single-center study, including adults (≥18 years) with type 3 SMA under nusinersen for > 22 months. We reported on motor scores and spirometry parameters. RESULTS: Ten patients were included, with a median follow-up of 34 months (range = 22-46). Four patients (40%) were walkers. None used non-invasive ventilation. In Revised Upper Limb Module (RULM) and Expanded Hammersmith Functional Motor Scale (HFMSE), difference of medians increased at 6, 22 and 46 months comparing to baseline (-0.5 vs. + 1.5 vs. + 2.5 in RULM; + 4.0 vs. + 7.5 vs. + 6.0 in HFMSE). Two (50%) walkers presented a clinically meaningful improvement in 6-min walk distance. We did not report any clinically meaningful decrement in motor scores. Spirometry parameters showed an increasing difference of medians in maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) (-3 vs. + 13.4 vs. + 28.7 percentage points of predicted value for MIP; + 11.8 vs. + 13.1 vs. 13.3 percentage points of predicted value for MEP). DISCUSSION: Our cohort supports a sustained benefit of nusinersen in adults with type 3 SMA, in motor and respiratory function. Multicentric studies are still warranted.
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Oligonucleótidos , Atrofias Musculares Espinales de la Infancia , Humanos , Masculino , Femenino , Oligonucleótidos/uso terapéutico , Oligonucleótidos/farmacología , Adulto , Estudios Retrospectivos , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Atrofias Musculares Espinales de la Infancia/fisiopatología , Estudios Longitudinales , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Estudios de SeguimientoRESUMEN
BACKGROUND: Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients. MATERIAL AND METHODS: A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed. RESULTS: Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited. CONCLUSIONS: Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.
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Diafragma , Electromiografía , Enfermedad del Almacenamiento de Glucógeno Tipo II , Neuronas Motoras , Debilidad Muscular , Nervio Frénico , Humanos , Enfermedad del Almacenamiento de Glucógeno Tipo II/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo II/fisiopatología , Masculino , Diafragma/fisiopatología , Femenino , Persona de Mediana Edad , Debilidad Muscular/etiología , Debilidad Muscular/fisiopatología , Nervio Frénico/fisiopatología , Neuronas Motoras/fisiología , Neuronas Motoras/patología , Adulto , Conducción Nerviosa/fisiología , Fibras Musculares Esqueléticas/patología , Fibras Musculares Esqueléticas/fisiología , Anciano , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/fisiopatología , Estudios Prospectivos , Potenciales de Acción/fisiologíaRESUMEN
Hydroxyapatite (HA) is a biomaterial widely used in clinical applications and pharmaceuticals. The literature on HA-based materials studies is focused on chemical characterization and biocompatibility. Generally, biocompatibility is analyzed through adhesion, proliferation, and differentiation assays. Fewer studies are looking for genotoxic events. Thus, although HA-based biomaterials are widely used as biomedical devices, there is a lack of literature regarding their genotoxicity. This systematic review was carried out following the PRISMA statement. Specific search strategies were developed and performed in four electronic databases (PubMed, Science Direct, Scopus, and Web of Science). The search used "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND genotoxicity OR genotoxic OR DNA damage" and "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND mutagenicity OR mutagenic OR DNA damage" as keywords and articles published from 2000 to 2022, after removing duplicate studies and apply include and exclusion criteria, 53 articles were identified and submitted to a qualitative descriptive analysis. Most of the assays were in vitro and most of the studies did not show genotoxicity. In fact, a protective effect was observed for hydroxyapatites. Only 20 out of 71 tests performed were positive for genotoxicity. However, no point mutation-related mutagenicity was observed. As the genotoxicity of HA-based biomaterials observed was correlated with its nanostructured forms as needles or rods, it is important to follow their effect in chronic exposure to guarantee safe usage in humans.
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Materiales Biocompatibles , Durapatita , Humanos , Durapatita/toxicidad , Durapatita/química , Materiales Biocompatibles/toxicidad , Hidroxiapatitas , Daño del ADN , Mutágenos/toxicidadRESUMEN
Nonmissile penetrating spine injury represents a small percentage of spinal cord injuries (SCIs), estimated at 0.8% in Western countries. This paper presents a detailed case report of a 28-year-old man with a history of substance use who suffered multiple injuries following a violent incident. The patient was found with a knife embedded in his thoracic spine, prompting immediate medical intervention. Computed tomography and postoperative magnetic resonance imaging revealed the extent of spinal cord and anatomical involvement. A thorough physical medicine and rehabilitation evaluation was conducted post-surgery, leading to a diagnosis of Brown-Séquard syndrome with associated sensorimotor deficits. This paper highlights the challenges posed by penetrating SCIs while reviewing the literature.
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A blend refers to the combination of two or more components to achieve properties that are superior to those found in the individual products used for their production. Gracilaria birdiae agaran (SPGb) and chromium picolinate (ChrPic) are both antioxidant agents. However, there is no documentation of blends that incorporate agarans and ChrPic. Hence, the objective of this study was to generate blends containing SPGb and ChrPic that exhibit enhanced antioxidant activity compared to SPGb or ChrPic alone. ChrPic was commercially acquired, while SPGb was extracted from the seaweed. Five blends (B1; B2; B3; B4; B5) were produced, and tests indicated B5 as the best antioxidant blend. B5 was not cytotoxic or genotoxic. H2O2 (0.6 mM) induced toxicity in fibroblasts (3T3), and this effect was abolished by B5 (0.05 mg·mL-1); neither ChrPic nor SPGb showed this effect. The cells also showed no signs of toxicity when exposed to H2O2 after being incubated with B5 and ChrPic for 24 h. In another experiment, cells were incubated with H2O2 and later exposed to SPGb, ChrPic, or B5. Again, SPGb was not effective, while cells exposed to ChrPic and B5 reduced MTT by 100%. The data demonstrated that B5 has activity superior to SPGb and ChrPic and points to B5 as a product to be used in future in vivo tests to confirm its antioxidant action. It may also be indicated as a possible nutraceutical agent.
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Gracilaria , Rhodophyta , Algas Marinas , Antioxidantes/farmacología , Peróxido de Hidrógeno/farmacología , VerdurasRESUMEN
Copaiba oil has been largely used due to its therapeutic properties. Nanocapsules were revealed to be a great nanosystem to carry natural oils due to their ability to improve the bioaccessibility and the bioavailability of lipophilic compounds. The aim of this study was to produce and characterize copaiba oil nanocapsules (CopNc) and to evaluate their hemocompatibility, cytotoxicity, and genotoxicity. Copaiba oil was chemically characterized by GC-MS and FTIR. CopNc was produced using the nanoprecipitation method. The physicochemical stability, toxicity, and biocompatibility of the systems, in vitro, were then evaluated. Β-bisabolene, cis-α-bergamotene, caryophyllene, and caryophyllene oxide were identified as the major copaiba oil components. CopNc showed a particle size of 215 ± 10 nm, a polydispersity index of 0.15 ± 0.01, and a zeta potential of -18 ± 1. These parameters remained unchanged over 30 days at 25 ± 2 °C. The encapsulation efficiency of CopNc was 54 ± 2%. CopNc neither induced hemolysis in erythrocytes, nor cytotoxic and genotoxic in lung cells at the range of concentrations from 50 to 200 µg·mL-1. In conclusion, CopNc showed suitable stability and physicochemical properties. Moreover, this formulation presented a remarkable safety profile on lung cells. These results may pave the way to further use CopNc for the development of phytotherapeutic medicine intended for pulmonary delivery of copaiba oil.
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INTRODUCTION AND HYPOTHESIS: This study aimed to compare the effectiveness of a hybrid telerehabilitation program with a traditional face to face model in women with stress urinary incontinence (SUI) and mixed incontinence (MUI) with a predominance of SUI. The authors hypothesized that home pelvic floor muscle training (PFMT) would have a similar benefit to outpatient PFMT. METHODS: Parallel randomized controlled trial including 58 patients consecutively admitted to a tertiary academic hospital for pelvic floor rehabilitation consultation from 1 January to 30 April 2021 for conservative treatment of UI. Participants randomized to the intervention were submitted to a 12-week PFMT program: (1) a hybrid telerehabilitation program of two individual face-to-face sessions followed by 2-weekly sessions of video-telerehabilitation with a follow-up by a specialized physiotherapist, including one individual face-to-face session at 8 weeks; (2) a re-evaluation teleconsultation at 6 and 16 weeks; (3) a face-to-face consultation at 12 weeks. The control group had two initial individual sessions followed by twice-weekly group classes, and consultations were face to face. The primary outcome measure (at baseline and 12 weeks) was UI-related quality of life using the Portuguese Version of the King's Health Questionnaire. RESULTS: At baseline the intervention (n = 18) and control (n = 17) groups were similar. UI-related quality of life significantly improved in both the intervention and control groups betweenbaseline (T0) and the end of the 12-week PFMT program (T12) (p = 0.002, p < 0.001, respectively), although the magnitude of the improvement was not significantly different between groups (-10.0 vs. -9.5 points, p = 0.918, respectively). CONCLUSION: This hybrid telerehabilitation protocol showed effectiveness comparable to the traditional model in improving UI-related quality of life. Trial registration at www. CLINICALTRIALS: gov , no. NCT05114395.
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COVID-19 , Telerrehabilitación , Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Humanos , Femenino , Calidad de Vida , Pandemias , Terapia por Ejercicio/métodos , Incontinencia Urinaria/terapia , Incontinencia Urinaria de Esfuerzo/terapia , Resultado del TratamientoRESUMEN
Bacterial infections have become a global concern, stimulating the growing demand for natural and biologically safe therapeutic agents with antibacterial action. This study was evaluated the genotoxicity of the trypsin inhibitor isolated from tamarind seeds (TTI) and the antibacterial effect of TTI theoric model, number 56, and conformation number 287 (TTIp 56/287) and derived peptides in silico. TTI (0.3 and 0.6 mg.mL-1) did not cause genotoxicity in cells (p > 0.05). In silico, a greater interaction of TTIp 56/287 with the Gram-positive membrane (GP) was observed, with an interaction potential energy (IPE) of -1094.97 kcal.mol-1. In the TTIp 56/287-GP interaction, the Arginine, Threonine (Thr), and Lysine residues presented lower IPE. In molecular dynamics (MD), Peptidotrychyme59 (TVSQTPIDIPIGLPVR) showed an IPE of -518.08 kcal.mol-1 with the membrane of GP bacteria, and the Thr and Arginine residues showed the greater IPE. The results highlight new perspectives on TTI and its derived peptides antibacterial activity.
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Tamarindus , Inhibidores de Tripsina , Inhibidores de Tripsina/farmacología , Tamarindus/química , Péptidos/química , Semillas/química , Antibacterianos/farmacología , Antibacterianos/análisis , Arginina/análisis , Arginina/químicaRESUMEN
Sulfated polysaccharides (SPS) from seaweeds have great biochemical and biotechnological potential. This study aimed to investigate the effect of SPS isolated from the seaweed Caulerpa sertularioides on adipogenic differentiation as a possible alternative treatment for obesity. The SPS-rich extract from the seaweed C. sertularioides was fractioned into three SPS-rich fractions (F0.5; F0.9; and F1.8) chemically characterized. Among these four samples, only F0.9 showed a significant inhibitory effect on adipogenesis of 3T3-L1 preadipocytes. Ten SPS-rich fractions were isolated from F0.9 through ion-exchange chromatography. However, only the fraction (CS0.2) containing a sulfated glucan was able to inhibit adipogenesis. CS0.2 reduces lipid accumulation and inhibits the expression of key adipogenic (PPARγ, C/EBPß, and C/EBPα) and lipogenic markers (SREBP-1c, Fabp4, and CD36). The data points to the potential of sulfated glucan from C. sertularioides for the development of functional approaches in obesity management.
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Caulerpa , Algas Marinas , Células 3T3-L1 , Adipocitos , Adipogénesis , Animales , Caulerpa/metabolismo , Glucanos/farmacología , Ratones , PPAR gamma/metabolismo , Polisacáridos/metabolismo , Polisacáridos/farmacología , Algas Marinas/química , Sulfatos/farmacologíaRESUMEN
The extravasation of doxorubicin, a cytostatic from the anthracycline group, is a rare and feared complication of intravenous chemotherapy due to tissue toxicity of these drugs. We describe a case of a 64-year-old woman with breast cancer undergoing adjuvant chemotherapy with doxorubicin and cyclophosphamide using a tunneled central catheter. After a chemotherapy cycle, the patient developed cough, dyspnoea and chest pain, due to a pleural effusion secondary to cytostatic leakage. A pleural drainage was placed and dexrazoxone was administred with resolution of the condition. The authors wish to highlight that the use of dexrazoxone should be considered after intra-pleural extravasation of anthracyclines given its effectiveness in preventing tissue damage and long-term sequelae in peripheral extravasation.
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Antraciclinas , Citostáticos , Antraciclinas/efectos adversos , Antibióticos Antineoplásicos/efectos adversos , Doxorrubicina/efectos adversos , Extravasación de Materiales Terapéuticos y Diagnósticos , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The present study evaluated the cytotoxicity, antioxidant potential, and antimicrobial effect on the antibiotic activity modulation of gelatin nanoparticles containing buriti oil (OPG). The cytotoxicity analysis was performed on Chinese Hamster Ovary Cells (CHO) using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. The antioxidant potential of buriti oil and OPG was determined by total antioxidant capacity, reducing power, and the ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) test. The modulating antimicrobial activity was evaluated by determining the minimum inhibitory concentration (MIC) concentration against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, gentamicin and norflaxacillin. The nanoformulation of OPG did not show a cytotoxic effect on CHO cells and had a higher antioxidant potential than free buriti oil (p<0.05). The combination of antibiotics with free buriti oil and OPG was more efficient in inhibiting E. coli and P. aeruginosa than isolated norfloxacillin and gentamicin (p<0.05). Regarding the inhibition of S. aureus, OPG in combination with norfloxacillin reduced MIC by 50%. Nanoencapsulation was a viable alternative to enhance functionality and adding commercial value to buriti oil.
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Antioxidantes , Arecaceae , Animales , Antibacterianos/farmacología , Antioxidantes/farmacología , Células CHO , Carotenoides , Cricetinae , Cricetulus , Escherichia coli , Gelatina , Gentamicinas/farmacología , Pruebas de Sensibilidad Microbiana , Aceites de Plantas , Staphylococcus aureus , PorcinosRESUMEN
Studies on the effect of sulfated polysaccharides from seaweed on bone regeneration have increased in recent years. However, there is no consensus on how to use them and their real effectiveness in that process. Thereby, we carried out a systematic review to answer the question "Do the sulfated polysaccharides from seaweeds promote osteogenesis?". Searches were performed in Pubmed, Scopus, and Web of Knowledge databases. A total of 599 articles were selected, resulting in 14 eligible studies. Results showed that the sulfated polysaccharides from seaweeds increase the osteogenic markers evaluated. Nevertheless, due to the lack of standardization on protocols used, the results should be cautiously interpreted. In addition, studies using animal models are still scarce, and the results with cellular models cannot always be extrapolated to systems that are more complex. Despite the study limitations, the use of sulfated polysaccharides appears to promote in vitro osteogenesis and enhance bone regeneration.
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Algas Marinas , Sulfatos , Animales , Regeneración Ósea , Polisacáridos/farmacología , Sulfatos/farmacología , Óxidos de AzufreRESUMEN
INTRODUCTION AND OBJECTIVES: Pulmonary endarterectomy (PEA) is a potentially curative procedure in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study reports the initial experience of a Portuguese PH center with patients undergoing PEA at an international surgical reference center. METHODS: Prospective observational study of consecutive CTEPH patients followed at a national PH center, who underwent PEA at an international surgical reference center between October 2015 and March 2019. Clinical, functional, laboratory, imaging and hemodynamic parameters were obtained in the 12 months preceding the surgery and repeated between four and six months after PEA. RESULTS: 27 consecutive patients (59% female) with a median age of 60 (49-71) years underwent PEA. During a median follow-up of 34 (21-48) months, there was an improvement in functional class in all patients, with only one cardiac death. From a hemodynamic perspective, there was a reduction in mean pulmonary artery pressure from 48 (42-59)â¯mmHg to 26 (22-38)â¯mmHg, an increase in cardiac output from 3.3 (2.9-4.0)â¯L/min to 4.9 (4.2-5.5)â¯L/min and a reduction in pulmonary vascular resistance from 12.1 (7.2-15.5)â¯uW to 3.5 (2.6-5,2)â¯uW. During the follow-up, 44% (n=12) of patients had no PH criteria, 44% (n=12) had residual PH and 11% (n=3) had PH recurrence. There was a reduction of N-terminal pro-B-type natriureticpeptide from 868 (212-1730)â¯pg/mL to 171 (98-382)â¯pg/mL. Rright ventricular systolic function parameters revealed an improvement in longitudinal systolic excursion and peak velocity of the plane of the tricuspid ring from 14 (13-14)â¯mm and 9 (8-10)â¯cm/s to 17 (16-18)â¯mm and 13 (11-15)â¯cm/s, respectively. Of the 26 patients with preoperative right ventricular dysfunction, 85% (n=22) recovered. The proportion of patients on specific vasodilator therapy decreased from 93% to 44% (p<0.001) and the proportion of those requiring oxygen therapy decreased from 52% to 26% (p=0.003). The six-minute walk test distance increased by about 25% compared to the baseline and only eight patients had significant desaturation during the test. CONCLUSION: Pulmonary endarterectomy performed at an experienced high-volume center is a safe procedure with a very favorable medium-term impact on functional, hemodynamic and right ventricular function parameters in CTEPH patients with operable disease. It is possible for PH centers without PEA differentiation to refer patients safely and effectively to an international surgical center in which air transport is necessary.