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We report the case of a patient who comes to the emergency department with abdominal pain, oral intolerance and bloody stools, being diagnosed with intestinal obstruction secondary to a jejunal tumor with contained perforation. A laparotomy was performed with resection of the jejunal tumor and taking biopsies from lesions with similar characteristics in the rest of the small bowel compatible with monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). The monomorphic epitheliotropic intestinal T-cell lymphoma is a rare intestinal tumor with a poor prognosis that is characterized by the proliferation of intraepithelial lymphocytes. The abdominal symptoms are nonspecific and the known major complications are intestinal perforation and obstruction. There is no standard therapeutic approach, being a combination of surgical resection, chemotherapy and autologous stem cell transplant.
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Objectives The aim of this is to investigate the changes in body mass index (BMI) following knee arthroplasty and to evaluate their impact on patient-reported outcomes and functional evaluations. Methods This observational study included 90 patients who underwent total knee arthroplasty (TKA) and were followed up for a median period of 2.6 years. BMI measurements were recorded before and after surgery, and patient-reported outcomes and functional evaluations were assessed using standardized scales and tests. Results Following TKA, BMI increased statistically significantly (Wilcoxon signed-rank test, p < 0.000). In addition, half of the patients experienced an increase in BMI, with 32% moving up in their BMI category. However, there were no clinically significant differences in patient-reported outcomes or functional evaluations between the group that gained BMI and the group that maintained or lost BMI. Conclusion This study reveals that patients tend to have increased BMI following TKA. However, these BMI changes do not significantly impact patient-reported outcomes or functional evaluations. It underscores the importance of patient education regarding healthy lifestyle habits, including diet and physical activity, to address postoperative weight gain effectively.
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Background: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are effective treatments for severe knee and hip osteoarthritis. Historically, TKA has been associated with lower satisfaction than THA, but recent advances in knee surgery have led to lower dissatisfaction rates. This study aimed to compare the satisfaction and self-reported improvement in the quality of life of two cohorts of patients who underwent TKA and THA, respectively. Methods: This observational study compared two previously published cohorts of patients who underwent THA and TKA in a single university center. The Goodman scale was used to assess satisfaction and self-perception of improved quality of life after TKA and THA at a minimum one-year follow-up. Propensity score matching was used to balance age, gender, and follow-up between groups. Significance was set at 0.05. Results: The study included a total of 105 THAs and 131 TKAs. Both groups had high levels of satisfaction with pain relief, ability to do house/yard work, and overall satisfaction, with above 90% satisfaction rates. Regarding improvement in quality of life, both groups had 86% of patients reporting improvement as "much better." After propensity score matching, no significant difference was found between THA and TKA for any of the comparisons made using the Goodman scale. Conclusions: The study showed that both TKA and THA resulted in high levels of satisfaction and improvement in quality of life. There was no significant difference in satisfaction rates between TKA and THA, contrary to the historical trend of lower satisfaction rates for TKA.
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Terpenylquinones are mixed biogenesis primary or secondary metabolites widespread in Nature with many biological activities, including the antineoplastic cytotoxicity, that have inspired this work. Here, we present a cytotoxic structure-activity relationship of several diterpenylhydroquinone (DTHQ) derivatives, obtained from the natural labdane diterpenoid myrceocommunic acid used as starting material. Different structural modifications, that changed the functionality and stereochemistry of the decalin, have been implemented on the bicyclic core through epoxidation, ozonolysis or decarboxylation, and through induction of biomimetic breaks and rearrangements of the diterpene skeleton. All the isomers generated were completely characterized by spectroscopic procedures. The resulting compounds have been tested in vitro on cultured cancer cells, showing their relevant antineoplastic cytotoxicity, with GI50 values in the µM and sub-µM range. The rearranged compound 8 showed the best cytotoxic results, with GI50 at the submicromolar range, retaining the cytotoxicity level of the parent compounds. In this report, the versatility of the labdane skeleton for chemical transformation and the interest to continue using structural modifications to obtain new bioactive compounds are demonstrated.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células , Diterpenos/química , Hidroquinonas/química , Neoplasias/tratamento farmacológico , Humanos , Estrutura Molecular , Neoplasias/patologia , Células Tumorais CultivadasRESUMO
The efficacy of µ-opioid receptors (MOR) in neuropathic pain is low and with numerous side effects that limited their use. Chronic neuropathic pain is also linked with emotional disorders that aggravate the sensation of pain and which treatment has not been resolved. This study investigates whether the administration of an oxindole, 5-fluoro-2-oxindole, could inhibit the nociceptive and emotional behaviors and increase the effectiveness of morphine via modulating the microglia and activating the nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway and MOR expression. In C57BL/6 mice with neuropathic pain provoked by the total constriction of sciatic nerve we studied the effects of 10 mg/kg 5-fluoro-2-oxindole in: (i) the allodynia and hyperalgesia caused by the injury; (ii) the anxiety- and depressive-like behaviors; (iii) the local antinociceptive actions of morphine; (iv) the expression of CD11b/c (a microglial marker), the antioxidant and detoxificant enzymes Nrf2, heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO1), and of MOR in the spinal cord and hippocampus. Results showed that the inhibition of the main nociceptive symptoms and the anxiety- and depressive-like behaviors induced by 5-fluoro-2-oxindole were accompanied with the suppression of microglial activation and the activation of Nrf2/HO-1/NQO1 signaling pathway in the spinal cord and/or hippocampus. This treatment also potentiated the pain-relieving activities of morphine by normalizing the reduced MOR expression. This work demonstrates the antinociceptive, anxiolytic and antidepressant effects of 5-fluoro-2-oxindole, suggests a new strategy to enhance the antinociceptive actions of morphine and proposes a new mechanism of action of oxindoles during chronic neuropathic pain.
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Analgésicos Opioides/administração & dosagem , Morfina/administração & dosagem , Neuralgia/tratamento farmacológico , Oxindóis/administração & dosagem , Medição da Dor/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/metabolismo , Neuralgia/psicologia , Medição da Dor/métodos , Medição da Dor/psicologia , Resultado do TratamentoRESUMO
Chronic neuropathic pain is associated with anxiety- and depressive-like disorders. Its treatment remains a serious clinical problem due to the lack of efficacy of the available therapeutic modalities. We investigated if the activation of the transcription factor Nrf2 could modulate the nociceptive and emotional disorders associated with persistent neuropathic pain and potentiated the analgesic activity of morphine. The possible mechanisms implicated in these effects have been also evaluated. Therefore, in C57BL/6 mice with neuropathic pain induced by the chronic constriction of the sciatic nerve (CCI), we assessed the antinociceptive, anxiolytic, and anti-depressant effects of the repeated intraperitoneal administration of a Nrf2 inducer, sulforaphane (SFN), and the effects of this treatment on the local antinociceptive actions of morphine. The protein levels of Nrf2, heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase-1 (NQO1), CD11b/c (a microglial activator marker), mitogen-activated protein kinases (MAPK) and µ opioid receptors (MOR) in the spinal cord, prefrontal cortex and hippocampus from mice, at 28 days after CCI, were also evaluated. Our results showed that the repeated administration of SFN besides inhibiting nociceptive responses induced by sciatic nerve injury also diminished the anxiety- and depressive-like behaviors associated with persistent neuropathic pain. Moreover, SFN treatment normalized oxidative stress by inducing Nrf2/HO-1 signaling, reduced microglial activation and JNK, ERK1/2, p-38 phosphorylation induced by sciatic nerve injury in the spinal cord and/or hippocampus and prefrontal cortex. Interestingly, treatment with SFN also potentiated the antiallodynic effects of morphine in sciatic nerve-injured mice by regularizing the down regulation of MOR in the spinal cord and/or hippocampus. This study suggested that treatment with SFN might be an interesting approach for the management of persistent neuropathic pain and comorbidities associated as well as to improve the analgesic actions of morphine.
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The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts potent antioxidative and anti-inflammatory effects; however, its participation in the modulation of chronic inflammatory pain and on the antinociceptive effects of µ-opioid receptor (MOR) agonists has not been evaluated. We investigated whether the induction of Nrf2 could alleviate chronic inflammatory pain and augment the analgesic effects of morphine and mechanisms implicated. In male C57BL/6 mice with inflammatory pain induced by complete Freund's adjuvant (CFA) subplantarly administered, we assessed: 1) antinociceptive actions of the administration of 5 and 10 mg/kg of a Nrf2 activator, sulforaphane (SFN); and 2) effects of SFN on the antinociceptive actions of morphine and on protein levels of Nrf2, heme oxygenase 1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) enzymes, microglial activation and inducible nitric oxide synthase (NOS2) overexpression, as well as on mitogen-activated protein kinase (MAPK) and MOR expression in the spinal cord and paw of animals with inflammatory pain. Results showed that treatment with SFN inhibited allodynia and hyperalgesia induced by CFA and increased the local antinociceptive actions of morphine. This treatment also augmented the expression of Nrf2, HO-1, NQO1, and MOR, and inhibited NOS2 and CD11b/c overexpression and MAPK phosphorylation induced by inflammation. Thus, this study shows that the induction of Nrf2 might inhibit inflammatory pain and enhance the analgesic effects of morphine by inhibiting oxidative stress and inflammatory responses induced by peripheral inflammation. This study suggests the administration of SFN alone and in combination with morphine are potential new ways of treating chronic inflammatory pain.
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Analgésicos Opioides/administração & dosagem , Analgésicos/administração & dosagem , Dor Crônica/tratamento farmacológico , Isotiocianatos/administração & dosagem , Morfina/administração & dosagem , Fator 2 Relacionado a NF-E2/biossíntese , Animais , Dor Crônica/induzido quimicamente , Dor Crônica/metabolismo , Quimioterapia Combinada , Adjuvante de Freund/toxicidade , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/agonistas , Sulfóxidos , Resultado do TratamentoRESUMO
The idea of closed-loop interaction in in vitro and in vivo electrophysiology has been successfully implemented in the dynamic clamp concept strongly impacting the research of membrane and synaptic properties of neurons. In this paper we show that this concept can be easily generalized to build other kinds of closed-loop protocols beyond (or in addition to) electrical stimulation and recording in neurophysiology and behavioral studies for neuroethology. In particular, we illustrate three different examples of goal-driven real-time closed-loop interactions with drug microinjectors, mechanical devices and video event driven stimulation. Modern activity-dependent stimulation protocols can be used to reveal dynamics (otherwise hidden under traditional stimulation techniques), achieve control of natural and pathological states, induce learning, bridge between disparate levels of analysis and for a further automation of experiments. We argue that closed-loop interaction calls for novel real time analysis, prediction and control tools and a new perspective for designing stimulus-response experiments, which can have a large impact in neuroscience research.
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Eletrofisiologia/métodos , Neurofisiologia/métodos , Animais , Estimulação Elétrica/métodos , PeixesRESUMO
Diterpenylquinone/hydroquinone derivatives were prepared through Diels-Alder cycloaddition between natural myrcecommunic acid or its methyl ester and p-benzoquinone (p-BQ), using BF(3).Et(2)O as catalyst or under microwave (Mw) irradiation. Acetyl, methyl and benzyl derivatives of several diterpenylnaphthohydroquinone were prepared from cycloadducts following two basic synthetic strategies, either protection before aromatisation or viceversa. Some of them were further functionalised at the B-ring of the decaline core. Most of the new compounds were evaluated and some of them resulted cytotoxic against several tumour cell lines with IC(50) values under the microM level.