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1.
Am J Emerg Med ; 81: 99-104, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38718560

RESUMO

STUDY OBJECTIVES: The study aimed to compare the analgesic effect of USG-guided PENG (Peri capsular nerve group) block with Intravenous Nalbuphine hydrochloride (IVN) in patients with hip fracture coming to the emergency department (ED). The purpose was also to monitor the adverse effects and rescue analgesic requirements in both treatment modalities. METHODS: The study was an open-label randomised controlled trial (RCT) comparing PENG block versus IVN in treating patients with femoral head and neck fractures, as well as pubic rami fracture of the hip (HF). The participants in the PENG group received a USG-guided PENG block by injection of 25 ml of 0.25% bupivacaine, whereas the IVN group received 0.15 mg/kg of nalbuphine. An emergency physician with expertise in ultrasound-guided nerve blocks performed the PENG blocks. The primary outcome was to measure the improvement of the NRS (Numerical rating scale) score at 30 min in both static position (Patient-chosen position for the best comfort) and dynamic position (15-degree passive affected lower limb elevation). Secondary outcomes were to measure static and dynamic NRS pain scores at 2 h, 4 h, and 6 h after intervention in both groups. The requirement for rescue analgesia, adverse events and any block-related complications were also recorded. RESULTS: A total of 60 patients with HF were included in the final analysis. The static and dynamic NRS score was significantly lower in the PENG group compared to the IVN group at 30 min, 2 h, 4 h, and 6 h post-intervention. In the PENG group, the static NRS score was improved by 5.73 ± 1.17, while In the IVN group, the static NRS score was just improved by 2.13 ± 0.97 at 30 min. In the same duration, the Dynamic NRS score in the PENG group was improved by 6.13 ± 1.38, while In the IVN group, it improved just by 2.43 ± 1.28. Rescue analgesia was required in 50.0% of patients in the IVN group but none in the PENG group. Further, no block-related complications or adverse events were observed in the patients of the PENG group. CONCLUSION: The study provides evidence that the ultrasound-guided PENG block has a better analgesic effect and has fewer adverse events than IV opioids in patients with HF.

2.
J Ethnopharmacol ; 330: 118207, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38636573

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Benign prostatic hyperplasia (BPH), characterized by prostate enlargement due to cell proliferation, is a common urinary disorder in men over 50, manifesting as lower urinary tract symptoms (LUTS). Currently, several therapeutic options are accessible for treating BPH, including medication therapy, surgery and watchful waiting. Conventional drugs such as finasteride and dutasteride are used as 5α-reductase inhibitors for the treatment of BPH. However long-term use of these drugs is restricted due to their unpleasant side effects. Despite the range of available medical therapies, the effective treatment against BPH is still inadequate. Certain therapeutic plants and their phytochemicals have the aforementioned goals and work by regulating this enzyme. AIM OF THE STUDY: This review aims to provide a comprehensive insight to advancements in diagnosis of BPH, modern treatment methods and the significance of ethnobotanically relevant medicinal plants as alternative therapeutics for managing BPH. MATERIAL AND METHODS: A thorough and systematic literature search was performed using electronic databases and search engines such as PubMed, Web of Science, NCBI and SciFinder till October 2023. Specific keywords such as "benign prostatic hyperplasia", "medicinal plants", "phytochemicals", "pharmacology", "synergy", "ethnobotany", "5-alpha reductase", "alpha blocker" and "toxicology". By include these keywords, a thorough investigation of pertinent papers was assured, and important data about the many facets of BPH could be retrieved. RESULTS: After conducting the above investigation, 104 herbal remedies were found to inhibit Phosphodiesterase-5 (PDE-5) inhibition, alpha-blockers, or 5α -reductase inhibition effects which are supported by in vitro, in vivo and clinical trial studies evidence. Of these, 89 plants have ethnobotanical significance as alpha-blockers, alpha-reductase inhibition, or PDE-5 inhibition, and the other fifteen plants were chosen based on their ability to reduce BPH risk factors. Several phytocompounds, including, rutaecarpine, vaccarin, rutin, kaempferol, ß-sitosterol, quercetin, dicaffeoylquinic acid, rutaevin, and phytosterol-F have been reported to be useful for the management of BPH. The use of combination therapy offers a strong approach to treating long-term conditions compare to single plant extract drugs. Furthermore, several botanical combinations such as lycopene and curcumin, pumpkin seed oil and saw palmetto oil, combinations of extracts from Funtumia africana (Benth.) Stapf and Abutilon mauritianum (Jacq.) Medik., and Hypselodelphys poggeana (K.Schum.) Milne-Redh. and Spermacoce radiata (DC.) Sieber ex Hiern are also supported through in vitro and in vivo studies for managing BPH through recuperation in patients with chronic long-term illnesses, as measured by the International Prostate Symptom Score. CONCLUSION: The review proposes and endorses careful utilization of conventional medications that may be investigated further to discover possible PDE-5, 5 alpha-reductase, an alpha-blocker inhibitor for managing BPH. Even though most conventional formulations, such as 5 alpha-reductase, are readily available, systemic assessment of the effectiveness and mechanism of action of the herbal constituents is still necessary to identify novel chemical moieties that can be further developed for maximum efficacy. However, there exist abundant botanicals and medicinal plants across several regions of Africa, Asia, and the Americas, which can be further studied and developed for utilization as a potential phytotherapeutic for the management of BPH.


Assuntos
Compostos Fitoquímicos , Plantas Medicinais , Hiperplasia Prostática , Hiperplasia Prostática/tratamento farmacológico , Humanos , Masculino , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Animais , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia , Inibidores de 5-alfa Redutase/uso terapêutico , Inibidores de 5-alfa Redutase/farmacologia
3.
J Clin Apher ; 39(1): e22106, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38334167

RESUMO

INTRODUCTION: Donor vein assessment for the selection of good quality veins is crucial for a successful apheresis procedure. This study intends to find out the effectiveness of a vein assessment scoring tool (VST) used and found to be effective in selecting whole blood donors to reduce the difficulty in identifying good quality veins for the plateletpheresis procedure. MATERIALS AND METHODS: This was a prospective observational study on platelet apheresis donors with the application of a VST consisting of three vein descriptor parameters (vein visibility, vein palpability, and vein size) with 5 Likert-type responses constituting a score of 0-12 for each arm. Two vein assessors independently evaluated the vein in both arms and marked their responses blinded from each other as well from the principal investigator. The scores were then calculated and analyzed at the end of the study for their association with phlebotomy and procedural outcomes. RESULTS: A total of 190 donors were recruited. The mean scores for the arms with successful and failed phlebotomy were 9.1 and 9.4 (SD 2.3), respectively. The intra-class correlation Alpha Cronbach value was 0.834 and 0.837 for total scoring in the left arm and right arm, respectively, between the two assessors. Scores neither showed a correlation with other outcomes like low flow alarms, hematoma formation, number of phlebotomy attempts, and procedure completion. CONCLUSION: The study showed that the vein score tool did not truly predict the phlebotomy outcome in apheresis donors, though there was a good degree of inter-assessor reliability.


Assuntos
Plaquetoferese , Veias , Humanos , Plaquetoferese/métodos , Reprodutibilidade dos Testes , Doadores de Sangue , Flebotomia/métodos
4.
Cureus ; 15(11): e48623, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38084196

RESUMO

The objective of this meta-analysis was to compare outcomes between sacubitril/valsartan and enalapril in patients with heart failure. We performed this meta-analysis according to the guidelines reported in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two independent authors systematically searched online databases including PubMed, Cochrane Library, and Web of Science from inception till September 15, 2023. Outcomes assessed in this meta-analysis included all-cause mortality, cardiovascular mortality, and cardiovascular-related hospitalization. A total of nine studies were included in this meta-analysis. Pooled analysis showed that the risk of all-cause mortality was higher in patients receiving enalapril compared to patients receiving sacubitril/valsartan (risk ratio [RR]: 0.57; 95% CI: 0.31 to 1.04). Risk of cardiovascular mortality was significantly higher in the enalapril group compared to the sacubitril/valsartan group (RR: 0.75; 95% CI: 0.62 to 0.91). The risk of cardiovascular hospitalization was significantly higher in the enalapril group compared to the sacubitril/valsartan group (RR: 0.76; 95% CI: 0.66 to 0.86). In conclusion, our meta-analysis of nine studies underscores the superior clinical performance of sacubitril/valsartan compared to enalapril in managing patients with heart failure.

5.
CRISPR J ; 6(6): 527-542, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38108519

RESUMO

To protect against mobile genetic elements (MGEs), some bacteria and archaea have clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) adaptive immune systems. CRISPR RNAs (crRNAs) bound to Cas nucleases hybridize to MGEs based on sequence complementarity to guide the nucleases to cleave the MGEs. This programmable DNA cleavage has been harnessed for gene editing. Safety concerns include off-target and guide RNA (gRNA)-free DNA cleavages, both of which are observed in the Cas nuclease commonly used for gene editing, Streptococcus pyogenes Cas9 (SpyCas9). We developed a SpyCas9 variant (SpyCas9H982A) devoid of gRNA-free DNA cleavage activity that is more selective for on-target cleavage. The H982A substitution in the metal-dependent RuvC active site reduces Mn2+-dependent gRNA-free DNA cleavage by ∼167-fold. Mechanistic molecular dynamics analysis shows that Mn2+, but not Mg2+, produces a gRNA-free DNA cleavage competent state that is disrupted by the H982A substitution. Our study demonstrates the feasibility of modulating cation:protein interactions to engineer safer gene editing tools.


Assuntos
Clivagem do DNA , Edição de Genes , Domínio Catalítico , Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas , Endonucleases , Streptococcus pyogenes/genética
6.
Cureus ; 15(9): e45508, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37868478

RESUMO

Lung cancer is responsible for a significant number of cancer-related deaths worldwide. While various factors can lead to lung cancer, such as tobacco smoking, this article focuses on the relationship between sarcoidosis, a multisystem granulomatous disorder, and lung neoplasm. To investigate this association, the authors conducted a literature search using relevant keywords. The analysis of these reports concluded that while Sarcoidosis and lung cancer together is rare, it is possible. The presenting symptoms, age, gender, and diagnostic procedures of each case should be evaluated, and appropriate diagnostic procedures should be carried out to determine the appropriate treatment for each patient. Clinicians need to be aware of the possibility of these two diseases co-occurring, as they can impact the management of the patient's condition, whether it is curative or palliative. It is essential to rule out metastatic cancer in individuals with sarcoidosis-like clinical and radiographic features.

7.
Cureus ; 15(9): e44841, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809175

RESUMO

It is well established that people with autism spectrum disorder (ASD) have significantly higher rates of social anxiety, given that most autistic individuals experience socio-communication impairments, a deficit in social competence, and their experience in social engagement situations often leads to discomfort in social settings. Literature also finds that individuals on the spectrum are often at a higher risk of developing social anxiety, which is often misinterpreted as social anxiety disorder (SAD) leading to delays in the clinical diagnosis of ASD. Hence, an improved understanding of specific factors that put ASD individuals at risk of developing social anxiety will aid research to differentiate between social anxiety among individuals with ASD compared to non-ASD individuals facing social anxiety in general. This systematic review study focuses on empirical literature that provides evidence for reasons contributing to social anxiety among individuals with ASD. Following the systematic review methodology, the study evaluates 10 research papers. The results revealed several correlations that can be useful in helping explain why individuals with ASD are at a higher risk of developing SAD. Individuals with ASD often suffer severe social anxiety because they struggle to understand social cues, maintain eye contact, interpret non-verbal cues like facial expressions or body language, or participate in reciprocal conversation. Other cognitive factors include a preference toward predictable situations, intolerance for uncertainty, and a tendency toward rigid thinking patterns. Unpredictability in social settings often heightens anxiety levels in ASD individuals, making them avoid such situations. Other risk factors include emotional recognition impairments and reduced social competence. These findings serve as a guide to developing better intervention strategies to help individuals with ASD to overcome social anxiety.

8.
Emerg Infect Dis ; 29(9): 1900-1903, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37610238

RESUMO

We describe a case in Australia of human neural larva migrans caused by the ascarid Ophidascaris robertsi, for which Australian carpet pythons are definitive hosts. We made the diagnosis after a live nematode was removed from the brain of a 64-year-old woman who was immunosuppressed for a hypereosinophilic syndrome diagnosed 12 months earlier.


Assuntos
Ascaridoidea , Larva Migrans , Feminino , Animais , Humanos , Pessoa de Meia-Idade , Larva Migrans/diagnóstico , Austrália , Encéfalo , Hospedeiro Imunocomprometido
9.
Cureus ; 15(7): e41472, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37546138

RESUMO

Background Assessing patients' quality of life has received increasing attention, mainly because questions have been raised regarding the direct benefits of the treatment provided. Hence, clinical outcomes and quality of life must be measured after chronic venous disease treatment. The primary objective of the study was to assess the improvement in clinical outcome and improvement in quality of life using the revised venous clinical severity score and chronic venous insufficiency questionnaire-14, respectively, in patients with varicose veins undergoing Trendelenburg's surgery and subfascial ligation of perforators. The secondary objective was to identify the relationship between the revised venous clinical severity score and the chronic venous insufficiency questionnaire-14 score. Method The present study is a single-center, prospective cohort study to assess the clinical improvement and quality of life in patients with varicose veins undergoing Trendelenburg surgery and subfascial ligation of perforators. All the study participants were evaluated preoperatively with the clinical, etiological, anatomical, and pathophysiological stage of the disease, revised venous clinical severity score for the clinical severity, and the chronic venous insufficiency questionnaire-14 questionnaire for the quality of life. The study participants were reviewed 90 days after surgery and reassessed for clinical severity and quality of life, both scores. Results Of the 87 screened varicose vein patients, 52 were included in the study. However, one patient was lost to follow-up. There were 38 (74.5%) males and 13 (25.5%) females. There was a significant difference in the preoperative and postoperative mean revised venous clinical severity score of the C3, C4, and C6 stages of the disease (p-value = <0.01). There was a significant difference in the mean preoperative and postoperative chronic venous insufficiency questionnaire-14 score in C3, C4, and C6 (p-value = <0.01). There was a significant difference in the median preoperative and postoperative revised venous clinical severity score (p-value = <0.01). There was a considerable difference in the mean preoperative and postoperative chronic venous insufficiency questionnaire-14 score (p-value = <0.01). The correlation coefficient between the preoperative chronic venous insufficiency questionnaire-14 score and the revised venous clinical severity score was 0.26 (p-value = 0.58), and the correlation coefficient between the postoperative chronic venous insufficiency questionnaire-14 score and the revised venous clinical severity score was 0.42 (p-value = <0.01).  Conclusion Patients undergoing Trendelenburg's surgery and subfascial ligation of perforators for varicose veins significantly improved the clinical severity and quality of life. There was significant improvement among the overall revised venous clinical severity score and chronic venous insufficiency questionnaire-14 score after surgery among the different clinical classes. There was no preoperative correlation between the revised venous clinical severity score and the chronic venous insufficiency questionnaire-14 score. However, there was a significant correlation between the postoperative revised venous clinical severity score and chronic venous insufficiency questionnaire-14 score.

10.
J Clin Med ; 12(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37629273

RESUMO

The association and interaction between the central nervous system (CNS) and enteric nervous system (ENS) is well established. Essentially ENS is the second brain, as we call it. We tried to understand the structure and function, to throw light on the functional aspect of neurons, and address various disease manifestations. We summarized how various neurological disorders influence the gut via the enteric nervous system and/or bring anatomical or physiological changes in the enteric nervous system or the gut and vice versa. It is known that stress has an effect on Gastrointestinal (GI) motility and causes mucosal erosions. In our literature review, we found that stress can also affect sensory perception in the central nervous system. Interestingly, we found that mutations in the neurohormone, serotonin (5-HT), would result in dysfunctional organ development and further affect mood and behavior. We focused on the developmental aspects of neurons and cognition and their relation to nutritional absorption via the gastrointestinal tract, the development of neurodegenerative disorders in relation to the alteration in gut microbiota, and contrariwise associations between CNS disorders and ENS. This paper further summarizes the synergetic relation between gastrointestinal and neuropsychological manifestations and emphasizes the need to include behavioral therapies in management plans.

12.
Life Sci ; 329: 121935, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37442415

RESUMO

AIMS: Insulin action is intertwined with changing levels of glucose and counter-regulatory hormone glucagon. While insulin lowers blood sugar level, glucagon raises it by promoting the breakdown of the stored glycogen in liver and releases glucose into the bloodstream. The hormones insulin and glucagon are key in the pathogenesis of type 2 diabetes (T2D). Insulin resistance is a primary predisposing factor for diabetes. Phosphorylation of insulin signaling molecules is altered in the insulin-resistant state. However, ubiquitin (Ub) modifications in insulin-resistant state are relatively understudied. To dissect the underlying mechanisms, we performed a proteomics study on hepatoma cells to study the regulation of ubiquitination by insulin and glucagon. MATERIALS AND METHODS: We performed western blotting, immunoprecipitations, and affinity pull down using tandem Ub binding entities (TUBE) reagents on hepatoma cells treated with insulin or glucagon. Next, we performed MS/MS analysis on Ub-linkage specific affinity pull down samples. Gene ontology analysis and protein-protein interaction network analysis was performed using DAVID GO and STRING db, respectively. KEY FINDINGS: The ubiquitination pattern of total Ub, K48-linked Ub, and K63-linked Ub was altered with the treatment of hormones insulin and glucagon. Ubiquitination in immunoprecipitated samples showed enrichment with total Ub and K48-linked Ub but not with K63-linked Ub. Ubiquitination by treatment with hormones mainly enriched key signaling pathways MAPK, Akt, oxidative stress etc. SIGNIFICANCE: Our study identified key altered proteins and signal transduction pathways which aids in understanding the mechanisms of hormonal action on ubiquitination and identify new therapeutic targets for T2D.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Humanos , Ubiquitina/metabolismo , Glucagon/metabolismo , Insulina/farmacologia , Insulina/metabolismo , Proteômica , Espectrometria de Massas em Tandem , Ubiquitinação
13.
Saudi J Anaesth ; 17(2): 263-265, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37260637

RESUMO

The radial artery is the most common choice for arterial cannulation, coronary interventions, and various interventional radiological procedures. Here, we describe a case of unilateral duplication of the radial artery detected during radial artery cannulation using point-of-care ultrasonography (POCUS). The duplication of the radial artery in the forearm can hinder trans-radial access secondary to variations in the diameter. An actual duplication also carries a high risk of accidental injury to the arterial wall during routine invasive procedures and other forearm procedures such as free flap construction. POCUS is invaluable for detecting arterial anomalies before proceeding with any interventional procedures.

14.
Antimicrob Agents Chemother ; : e0050023, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37314343

RESUMO

With limited and often toxic treatment options, carbapenem-resistant Gram-negative infections are associated with significant mortality. Cefepime-zidebactam is a promising antibiotic option undergoing a phase 3 trial that has activity against diverse antibiotic-resistant mechanisms in Gram-negative pathogens due to its ß-lactam enhancer mechanism, mediating multiple PBP binding. We report a case of disseminated infection caused by a New Delhi metallo-ß-lactamase-producing, extensively drug-resistant Pseudomonas aeruginosa isolate in a patient with acute T-cell leukemia, successfully managed with cefepime-zidebactam as a salvage therapy.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Infecções por Pseudomonas , Adulto , Humanos , Pseudomonas aeruginosa/metabolismo , Infecções por Pseudomonas/tratamento farmacológico , Terapia de Salvação , Cefalosporinas/uso terapêutico , Antibacterianos/uso terapêutico , beta-Lactamases/genética , beta-Lactamases/metabolismo , Compostos Azabicíclicos/uso terapêutico , Testes de Sensibilidade Microbiana
16.
J Mycol Med ; 33(3): 101406, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37229913

RESUMO

Cryptococcal meningitis is a life-threatening infection commonly seen in patients with advanced HIV infection and solid organ transplant recipients. We report a case of cryptococcal meningitis with immune reconstitution syndrome (IRIS) who presented to us with a headache and complete loss of vision in the left eye. He was managed with antifungals and a short course of steroids, and he regained vision completely. In the hospital, he developed complications including tacrolimus toxicity, fluconazole-induced QT prolongation, and flucytosine-induced thrombocytopenia. Our case demonstrates the importance of a multidisciplinary approach in the management of complex cases like cryptococcal meningitis in solid organ transplant recipients.


Assuntos
Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Meningite Criptocócica , Transplante de Órgãos , Masculino , Humanos , Meningite Criptocócica/complicações , Meningite Criptocócica/tratamento farmacológico , Infecções por HIV/complicações , Síndrome Inflamatória da Reconstituição Imune/complicações , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Antifúngicos/efeitos adversos , Corticosteroides , Cegueira , Transplante de Órgãos/efeitos adversos
17.
Am J Emerg Med ; 63: 94-101, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332503

RESUMO

STUDY OBJECTIVE: To compare the analgesic efficacy of ultrasound-guided selective peripheral nerve block (PNB) and sub-dissociative dose ketamine (SDK) for management of acute pain in patients with extremity injuries presenting to the emergency department (ED). METHODS: This prospective, open-label randomized clinical trial was conducted in the ED of a tertiary care Institute. The patients were provided with either ultrasound-guided selective PNB or SDK. The primary outcome was a reduction in pain in numerical rating scale (NRS) by at least 3 points without rescue analgesia. The secondary outcomes were the need for rescue analgesia, adverse events, and patient satisfaction on either arm. RESULTS: A total of 111 patients with isolated traumatic extremity injuries were included in the final analysis. The NRS score was significantly lower in the PNB group compared to the SDK group at 30, 60,120, 180-, and 240-min post-intervention [group ∼ time interaction, F (5, 647) = 21.53, p ≤ 0.001]. All the patients in the PNB group exhibited primary outcome (NRS ≥3 reductions) at 30 min post-intervention compared with 36 (65%) in the SDK group [-1.02(-1.422,0.622)]. Rescue analgesia was required in 10 (18%) patients in the SDK group compared to none in the PNB group [0.663(0.277,1.050)]. The decrease in NRS score from baseline at 30 min was significantly higher in PNB groups compared to the SDK group [-2.166(-2.640, -1.692)]. The most common side effect reported in the SDK group was dizziness 35(64%), followed by nausea 15(27%). None of the patients in the PNB group reported any complications. Patient satisfaction was higher in the PNB group than SDK group. CONCLUSION: The study provides evidence that ultrasound-guided PNB is superior to SDK in terms of its analgesic efficacy in the management of acute pain due to extremity injuries and is associated with higher patient satisfaction. The need for rescue analgesia was significantly less in the PNB group. SDK was associated with a high incidence of dizziness and nausea.


Assuntos
Dor Aguda , Analgesia , Ketamina , Bloqueio Nervoso , Humanos , Dor Aguda/terapia , Ketamina/administração & dosagem , Nervos Periféricos , Estudos Prospectivos , Bloqueio Nervoso/métodos , Ultrassonografia de Intervenção , Analgesia/métodos
18.
Cell Rep ; 41(6): 111596, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36351380

RESUMO

Targeting early-stage lung cancer is vital to improve survival. However, the mechanisms and components of the early tumor suppressor response in lung cancer are not well understood. In this report, we study the role of Toll-like receptor 2 (TLR2), a regulator of oncogene-induced senescence, which is a key tumor suppressor response in premalignancy. Using human lung cancer samples and genetically engineered mouse models, we show that TLR2 is active early in lung tumorigenesis, where it correlates with improved survival and clinical regression. Mechanistically, TLR2 impairs early lung cancer progression via activation of cell intrinsic cell cycle arrest pathways and the proinflammatory senescence-associated secretory phenotype (SASP). The SASP regulates non-cell autonomous anti-tumor responses, such as immune surveillance of premalignant cells, and we observe impaired myeloid cell recruitment to lung tumors after Tlr2 loss. Last, we show that administration of a TLR2 agonist reduces lung tumor growth, highlighting TLR2 as a possible therapeutic target.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Genes Supressores de Tumor , Pulmão/metabolismo , Senescência Celular/genética
19.
Pharm Res ; 39(11): 2871-2883, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36195821

RESUMO

PURPOSE: Glioblastoma multiforme (GBM) is a grade IV, highly proliferative, and malignant form of brain tumor with a 5-year survival rate at ~ 5%. Current treatment strategies for GBM include surgery, radiation, and chemotherapy. Major challenges in GBM management include difficulties in surgical resection due to brain's vital functions and GBM metastasis, development of resistance to temozolomide (TMZ), and protection of tumor by blood brain barrier (BBB). Therefore, we aimed to discover a novel therapeutic for GBM by targeting its metabolic reprogramming. METHOD: We screened metabolic inhibitors by their effects on GBM cell viability by MTT assay. We discovered an FDA-approved drug stiripentol (STP) in our screening of metabolic inhibitors in GBM cells. STP is used for Dravet syndrome (a rare epilepsy). We further tested efficacy of STP using proliferation assay, clonogenic assay, in vitro migration assay, cell cycle assay, apoptosis assay, and in U87 3D spheroids. We also tested the toxicity of STP, and combinations used in the study on normal human dermal fibroblasts. RESULTS: STP was effective in decreasing GBM cell viability, proliferation, clonogenic ability, and migration. Moreover, cell cycle changes were involved but robust apoptosis was absent in STP's anticancer effects. STP was effective in 3D spheroid models, and in TMZ-resistant cells. STP showed additive or synergistic effect with TMZ in different anticancer assays on GBM cells and was considerably less toxic in normal cells. CONCLUSION: Our results indicate that STP can be an effective GBM therapeutic that enhances the effects of TMZ on GBM cells. Importantly, STP reduced viability of TMZ-resistant cells. Our results warrant further studies in the mechanistic basis of STP's effects on GBM cells and the preclinical potential of STP in animal models.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Anticonvulsivantes/farmacologia , Reposicionamento de Medicamentos , Linhagem Celular Tumoral , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Apoptose , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos Alquilantes/uso terapêutico , Proliferação de Células , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Orthop Case Rep ; 12(3): 5-8, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36199918

RESUMO

Introduction: Osteoporosis is a known complication of prolonged steroid therapy. Osteoporotic fracture is common in such a scenario and poses several challenges in its management. We present a case of neglected proximal humerus fracture in a 57-year-old osteoporotic female and the difficulties encountered in its management. Case Report: A 57- year-old female, rheumatoid arthritis patient, is on steroids for the past ten years. Four years back, she sustained a fracture of the left humerus neck following a trivial trauma. The fracture was not managed by an orthopaedician and was treated by a general practitioner. She presented to us in a state of painless displaced non-union of fragments with severe osteoporosis. DEXA scan revealed severe osteoporosis. She was started on oral calcium, magnesium, and vitamin D supplementation. Along with oral supplementation, the patient was advised 20 mcg of Teriparatide subcutaneously once daily and single dose of Denosumab 60 mg subcutaneously. Non -vascularized free fibular graft was harvested from the ipsilateral lower limb. A five-hole PHILOS plate was used to fix the fracture. Intra-operatively, the humeral head appeared too indistinct under fluoroscopy leading to difficulty in estimating screw length. An indirect method was used to assess the screw length. The post-operative radiograph was satisfactory but radiograph after two weeks showed an un-displaced fracture adjacent to the distal end of the plate. It was decided to continue with conservative management by a "'U"' cast. A follow- up radiograph at three months showed complete union of the stress fracture at the distal end of the plate end and progressive union of the fracture at the primary site. But En- block pull-out of the locking plate was noticed in the distal fragment of the fracture in the follow-up radiograph at 9 months from surgery. The limb was further immobilized in an arm sling for more four weeks. At one year from operation, there was good union of fracture with acceptable shoulder movement. Conclusion: Osteoporotic fractures are often difficult to treat. Careful pre-operative planning, active osteoporosis management, good implant selection, careful bone handling, and judicious rehabilitation are key to avoid complications and achieve good functional outcome.

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