Conventional Pharmacological Therapy Research Articles

Feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array

Objective. Electrical stimulation of peripheral nerves has long been a treatment option to restore impaired neural functions that cannot be restored by conventional pharmacological therapies. Endovascular neurostimulation with stent-mounted electrode arrays is a promising and less invasive alternative to traditional implanted electrodes, which typically require invasive implantation surgery. In this study, we investigated the feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array and compared its performance to that of a commercially available pacing catheter. Approach. In acute animal experiments, a pacing catheter was implanted unilaterally in the femoral artery to stimulate the femoral nerve in a bipolar configuration. Electromyogram of the quadriceps and electroneurogram of a distal branch of the femoral nerve were recorded. After retrieval of the pacing catheter, a bipolar stent-mounted electrode array was implanted in the same artery and the recording sessions were repeated. Main Results. Stimulation of the femoral nerve was feasible with the stent-electrode array. Although the threshold stimulus intensities required with the stent-mounted electrode array (at 100–500 µs increasing pulse width, 2.17 ± 0.87 mA–1.00 ± 0.11 mA) were more than two times higher than the pacing catheter electrodes (1.05 ± 0.48 mA–0.57 ± 0.28 mA), we demonstrated that, by reducing the stimulus pulse width to 100 µs, the threshold charge per phase and charge density can be reduced to 0.22 ± 0.09 µC and 24.62 ± 9.81 µC cm−2, which were below the tissue-damaging limit, as defined by the Shannon criteria. Significance. The present study is the first to report in vivo feasibility and efficiency of peripheral nerve stimulation using an endovascular stent-mounted electrode array.

#2107 Therapeutic apheresis for the management of lipid disorders: a case series

Abstract Background and Aims Hypertriglyceridemia (HTG) is defined as the plasmatic concentration of triglycerides above 150 mg/dl. With a current prevalence ranging from 15% to 20% in clinical practice, it's a prevalent condition that´s increasing alongside other cardiovascular risk factors such as diabetes mellitus, obesity and hypertension. In most patients HTG is asymptomatic, except in certain circumstances such as hereditary HTG, which can present with skin lesions such as eruptive xanthomas and xanthelasmas. Another exception is severe HTG, which can manifest with pancreatitis. Pharmacological treatment for HTG is typically initiated when serum triglyceride levels exceed 885 mg/dl or when patients with a previous episode of pancreatitis. However, in cases of severe HTG (triglycerides > 1000 mg/dl), conventional pharmacological therapies become less effective. Therefore, alternative therapeutic interventions, such as apheresis, become increasingly relevant for the management of severe HTG. Current guidelines from the American Society of Apheresis (ASFA) consider the use of therapeutic plasmapheresis in patients with acute pancreatitis secondary to severe hypertriglyceridemia as a category III/grade 1C recommendation and that in most cases it is an adjunct to medical treatment. Case series Below, we describe a series of cases in which we used this technique to control metabolic in our center during the last year. Case 1 A 30-year-old man with familial primary hypertriglyceridemia, schizophrenia, and sporadic drinking, was admitted from the Emergency Department with a 24h long severe abdominal pain with difficult management and vomiting. After complementary analysis, acute edematous pancreatitis without necrosis was diagnosed. Given the analytical values (Table 1), therapeutic plasmapheresis was decided, with a plasma volume of 3.5 liters calculated with the patient's weight and hematocrit and using albumin as the replacement fluid. As a complication, and despite administration of heparin, the filter required replacement halfway through the session due to problems with transmembrane pressure. Two sessions were completed on consecutive days until clinical and analytical control of triglycerides was achieved. Case 2 A 55-year-old man with a history of mild dyslipidemia controlled with diet and hypertension, was admitted from the Emergency Department with abdominal pain of 12 hours duration. After completing the study and diagnosis of acute pancreatitis of probable HTG origin, a plasmapheresis session was completed with a volume of 3 liters, albumin replacement fluid and heparinization during the technique, without complications, along with triglyceride control after the procedure maintaining medical treatment. Case 3 A 62-year-old man with a history of familial HTG, bronchial hyperreactivity, and occasional drinking, was admitted with abdominal pain of 72 hours duration accompanied by nausea and vomiting. Complementary studies confirmed acute severe pancreatitis with hemodynamic and respiratory failure. Given the analytical findings, a plasmapheresis session was performed with a volume of 2.5 liters per weight and hematocrit, with albumin replacement and heparin as per protocol. Subsequent HTG control with medical treatment was achieved without the need for further apheresis sessions. Conclusion Cardiovascular disease is responsible for the death of more than 4 million people in Europe each year, 2.2 million women (55%) and 1.8 million men (45%). Lipoprotein apheresis has preventive effects on the progression of atherosclerosis in addition to being an effective technique for reducing LDL, so its indication in groups of patients with severe and primarily familial hypercholesterolemia is well established. In our center, the recent start of the control of apheresis techniques from Nephrology in metabolic diseases, although still with limited experience and a limited number of patients, may constitute a new field of work in the specialty itself and collaboration with the different hospital specialties to improve the prevention, control, and treatment of patients with a high cardiovascular risk.

If Art Were a Drug: Implications for Parkinson’s Disease

Parkinson’s disease (PD) is a chronic and complex neurodegenerative disorder. Conventional pharmacological or surgical therapies alone are often insufficient at adequately alleviating disability. Moreover, there is an increasing shift toward person-centered care, emphasizing the concept of “living well”. In this context, arts-based interventions offer great promise, functioning as platforms for creative expression that could provide novel mechanisms to promote quality of life. Here we present a qualitative review of arts-based interventions for PD, including music, dance, drama, visual arts, and creative writing. For each, we discuss their applications to PD, proposed mechanisms, evidence from prior studies, and upcoming research. We also provide examples of community-based projects. Studies to date have had relatively small sample sizes, but their findings suggest that arts-based interventions have the potential to reduce motor and non-motor symptoms. They may also empower people with PD and thereby address issues of self-esteem, foster personal problem-solving, and augment holistic well-being. However, there is a paucity of research determining optimal dosage and symptom-specific benefits of these therapies. If art were a drug, we would have to perform appropriately powered studies to provide these data before incorporating it into routine patient care. We therefore call for further research with properly designed studies to offer more rigorous and evidence-based support for what we intuitively think is a highly promising approach to support individuals living with PD. Given the possible positive impact on people’s lives, arts-based approaches merit further development and, if proven to be effective, systematic inclusion within integrated management plans.

Non-pharmacological Treatment for Nontuberculous Mycobacterial Pulmonary Disease.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) arises from the exposure of susceptible hosts to a diverse group of environmental mycobacteria. The emphasis on non-pharmacological strategies is motivated by widespread presence of nontuberculous mycobacteria (NTM) in various environments and the inconsistent success rates of pharmacological treatments. Modifiable factors contributing to NTM-PD development include impaired airway clearance, low body mass index, gastroesophageal reflux disease, and exposure to NTM habitats. This suggests that lifestyle and environmental modifications could affect disease development and progression. The review highlights several modalities that can modify the risk factors. Airway clearance techniques, informed by the "gel-on-brush" model of the bronchial epithelium, aims at enhancing mucociliary clearance and have potential in alleviating symptoms and potentially improving lung function. The impact of nutritional status is also examined, with a lower body mass index linked to an increased risk and progression of NTM-PD, indicating the importance of targeted nutritional support. Additionally, the theoretical and epidemiological links between gastroesophageal reflux disease and NTM-PD advocates for careful management of reflux episodes. Understanding the risk of NTM transmission through environmental exposure to contaminated water and soil is also crucial. Strategies to mitigate this risk, including effective water management and minimizing soil contact, are presented as vital preventive measures. In conclusion, the review supports the inclusion of non-pharmacological treatments within a comprehensive NTM-PD management strategy, alongside conventional pharmacological therapies. This integrated approach seeks to improve the overall understanding and handling of NTM-PD.

A Narrative Review on the Interplay between Blood Pressure, Anxiety/Depression, and Probiotics: Unraveling the Underlying Mechanisms

Abstract High blood pressure, or hypertension (HTN), is a major risk factor for cardiovascular disease and various chronic conditions. Recent research suggests that nutraceuticals can enhance the effectiveness of conventional pharmacological therapies. As a result, there is increasing interest in using therapeutic diets and diverse compounds to complement these treatments. Depression is a globally prevalent and debilitating disorder. Anxiety, on the other hand, is a state of heightened emotion that involves both psychological and physical changes, even without a clear cause. In addition to standard therapies, alternative approaches, including adjunctive therapies, are being explored. HTN and anxiety are closely linked conditions. Anxiety can temporarily increase blood pressure due to the body’s natural “fight or flight” response. However, if anxiety persists, it can lead to chronic HTN. Conversely, HTN can also increase the risk of anxiety by causing physical symptoms that can trigger anxiety. Moreover, medications commonly prescribed for HTN may have side effects that worsen anxiety symptoms. It is crucial to identify and offer affordable treatments and prevention methods for both conditions. Recently, there has been discussion about the use of probiotic supplements as an alternative treatment for reducing blood pressure and anxiety. These supplements contain active microorganisms that can provide benefits to the body when consumed in sufficient quantities. Numerous studies have explored the potential benefits of probiotics for individuals with HTN. Similarly, several studies have investigated the impact of probiotics on anxiety. However, the relationship between anxiety, HTN, and the effects of probiotics on these disorders is still a topic of debate. Given the conflicting evidence and the interplay between anxiety and blood pressure, we have chosen to create a comprehensive review article that thoroughly examines and provides a detailed description of the potential mechanisms involved in this connection.

Beneficial Properties and Sustainable Use of a Traditional Medicinal Plant: Griffonia simplicifolia

Since ancient times, medicinal plants have been a universal source of biologically active substances with high potential for the treatment of various diseases and disorders. For centuries, traditional communities have often relied on medicinal plants to treat health problems. Therefore, accurate information is required and knowledge about traditional medicinal plants requires evaluation, and great attention should be given to the possible integration of these plants as therapeutic agents or as complements to conventional pharmacological therapies in the healthcare system. Recently, Griffonia simplicifolia (DC.) Baill., initially used as a holistic remedy, has attracted attention from many researchers and consumers because of its multiple health-promoting effects. This growing interest prompted us to give an updated review of the botanical, geographical, historical, and therapeutic potentials of Griffonia simplicifolia (DC.) Baill. in terms of its in vitro and in vivo health effects, nutritional uses, and possible applications in line with biodiversity and sustainability concepts. This paper also presents a quantitative research analysis of the published studies related to this plant that are available in the literature. To retrieve the publications related to this plant, a bibliographic search was carried out using the Scopus database. The bibliometric data were extracted and processed using VOSviewer software (v.1.6.16, 2020). Technological possible applications in terms of patents request presented was also performed. A total of 1386 publications, from the year 1970 to the year 2021, were obtained by the literature search, and these had been collectively cited 38,805 times. The large amount of literature data available documents the interest in this plant’s use as a tool for integrating traditional holistic healing approach, e.g., using plants, herbs, and holistic remedies, into the healthcare system as supporting tools and/or therapeutic agents, which is a current worldwide challenge.

Role of Regenerative Therapeutics in Diabetic Peripheral Neuropathy: Current Advances and Future Prospects

Diabetes is a chronic metabolic condition that has far-reaching consequences for human health. If there is no appropriate therapeutic treatment, diabetic peripheral neuropathy might lead to foot ulceration and limb amputation. Conventional pharmacological therapy have weak anti-DPN activity. By stimulating nerve regeneration, addressing underlying causes of the disorder, and alleviating symptoms, stem cell therapy for diabetic peripheral neuropathy has the potential to alter the management of this debilitating illness. One of its most significant advantages is its ability to regenerate damaged nerves, as stem cells may differentiate into a variety of cell types, including neurons and supporting cells. Preclinical and early-phase clinical research has resulted in improvements in nerve conduction, pain alleviation, and sensory function in patients with diabetic peripheral neuropathy. Stem cell therapy can be tailored to each patient's specific ailment, ensuring personalized care that improves therapeutic outcomes. Future research may uncover further benefits and applications for stem cell treatment, such as refining stem cell source selection, experimenting with novel delivery systems, and capitalizing on tissue engineering advances. Combining stem cell therapy with gene editing or bioengineering procedures may improve regenerative potential in the treatment of diabetic peripheral neuropathy. To completely reap the benefits of stem cell therapy in diabetic peripheral neuropathy, obstacles must be overcome and treatment procedures must be improved. Stem cell therapy has the potential to revolutionize the treatment of diabetic peripheral neuropathy by encouraging nerve regeneration, and symptom relief. The present review discusses the noteworthy developments in various regenerative therapies for diabetic peripheral neuropathy.

Nanorobotic artificial blood components and its therapeutic applications: A minireview.

Numerous scientific and medical domains have been revolutionized by nanotechnology, opening up unprecedented opportunities for healthcare applications. Among these developments, the creation of nanorobots for artificial blood components is a novel field of research that seeks to overcome the constraints of conventional pharmacological therapy. This review article provides a comprehensive overview of the nanorobotic artificial blood components and their therapeutic uses. The article begins by outlining the core concepts of nanotechnology and nanorobotic systems, emphasizing their design and control methods. It then delves into various types of nanorobotic artificial blood components, such as oxygen transporters (artificial RBCs), clotting agents (artificial platelets), and immune modulators (artificial WBCs). It goes into detail about their properties, functioning, and capabilities, which allow them to replicate the physiological activities of actual blood components. The article also assesses the clinicaluses of artificial blood components in a variety of medical circumstances. It highlights their potential value in the management of certain blood-related diseases.

Carvacrol and its effect on cardiovascular diseases: From molecular mechanism to pharmacological modulation

Cardiovascular diseases (CVDs) affect worldwide and influence people from diverse cultures, socioeconomic status, ethnicities, and healthcare systems. The underlying pathogenesis of CVD predominately includes atherosclerotic plaques, which further lead to coronary artery disease and peripheral vascular diseases, resulting in stroke, arrhythmias, myocardial infarction, and many more. Conventional pharmacological therapies that treat CVDs are costly and have numerous side effects. Despite the effectiveness of these therapies, remarkable gaps remained in the treatment of CVDs. Consequently, traditional herbs and phytomedicines have revived interest as natural remedies. Phenolic monoterpene, carvacrol, was reported to have numerous pharmacological applications. This review aims to provide comprehensive, categorized, and updated mechanisms by which carvacrol shows its cardioprotective effect in various heart illnesses to analyze its therapeutic ability. Comprehensive literature forage was carried out, and the available information regarding carvacrol and CVDs was retrieved using scientific electronic search (PubMed, Google Scholar, and Web of Science). In this review, we focused on the therapeutic role and underlying mechanism of carvacrol in CVDs as per existing literature evidence. We highlighted the benefits of carvacrol in myocardial infarction, cardiac hypertrophy, hypertension, cardiac arrhythmia, sepsis-induced cardiomyopathy, drug-induced cardiotoxicity, and stroke/cerebral ischemic/reperfusion injury and enumerated the potential mechanism of action. Carvacrol may have shown efficacy against various CVDs by antioxidant and anti-inflammatory properties. Further detailed studies are required to translate the carvacrol from preclinical candidate to clinical hope.

Virtual screening and structure optimization of xanthine oxidase inhibitory peptides from whole protein sequences of Pacific white shrimp via molecular docking.

Xanthine oxidase (XO) inhibitory peptides are safer than conventional pharmacological therapy in relieving hyperuricemia. However, traditional enzymatic hydrolysis, separation, and purification techniques for bio-active peptide preparation are time-consuming, inefficient, and labor-intensive. In this study, molecular docking and BLAST were used to virtually screen XO inhibitory peptides from whole protein sequences of Pacific white shrimp according to the bio-active peptides database, and the structure of peptides was optimized based on the structure-effective relationship. Seven new XO inhibitory peptides were virtual screened rapidly from Pacific white shrimp, and YNITGW (IC50=9.78±0.13mM) showed the strongest activity. The results of YNITGW optimization showed that the insertion of Trp residue in the middle position of peptides could effectively enhance the activity. This study revealed that screening and optimizing peptides by molecular docking were a novel and feasible method to obtain bio-active peptides.

Effect of increase in heart rate after anthracycline chemotherapy on subsequent left ventricular dysfunction

BackgroundAnthracycline chemotherapy-related cardiac dysfunction is believed to be refractory to conventional pharmacological therapy and is associated with a poor prognosis. Increased heart rate (HR) is a known marker of cardiovascular outcomes for various categories of heart failure (HF). However, little interest has been expressed regarding increased HR after anthracycline chemotherapy. Aim of this study was to investigate the effect of increased HR soon after completion of anthracycline chemotherapy on subsequent left ventricular (LV) ejection fraction (LVEF) in cancer patients. MethodsWe studied 172 patients with breast cancer and malignant lymphoma with preserved LVEF (≥ 50 %) and sinus rhythm treated with anthracyclines. Electrocardiography was performed before and soon after completion of anthracycline chemotherapy (2.3 months), and echocardiography before and late after completion of anthracycline chemotherapy (10.5 months). ResultsHR significantly increased from 74.2 ± 14.2 bpm to 75.9 ± 13.2 bpm (P = 0.05) soon after completion of anthracycline chemotherapy, while LVEF subsequently significantly decreased from 65.3 ± 5.5 % to 62.4 ± 6.1 % (P < 0.01) late after completion of anthracycline chemotherapy. Patients whose HR increased ≥10 bpm subsequently showed a significantly greater decrease in LVEF than those whose HR increased <10 bpm [−4.9 % (−32.7 % - 10.8 %) vs. -2.2 % (−21.2 % - 12.9 %), p = 0.04]. Multivariable logistic regression analysis showed that an increase in HR soon after completion of anthracycline chemotherapy was independently associated with a subsequent decrease in LVEF (odds ratio: 1.022, 95 % confidential interval; 1.008–1.037, P = 0.002). ConclusionsOur findings may have a novel effect on the management of cancer patients scheduled for anthracycline chemotherapy.

Microbiota-gut-brain axis and ketogenic diet: how close are we to tackling epilepsy?

The microbiota-gut-brain axis refers to the intricate bidirectional communication between commensal microorganisms residing in the digestive tract and the central nervous system, along neuroendocrine, metabolic, immune, and inflammatory pathways. This axis has been suggested to play a role in several neurological disorders, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy, paving the way for microbiome-based intervention strategies for the mitigation and treatment of symptoms. Epilepsy is a multifaceted neurological condition affecting more than 50 million individuals worldwide, 30% of whom do not respond to conventional pharmacological therapies. Among the first-hand microbiota modulation strategies, nutritional interventions represent an easily applicable option in both clinical and home settings. In this narrative review, we summarize the mechanisms underlying the microbiota-gut-brain axis involvement in epilepsy, discuss the impact of antiepileptic drugs on the gut microbiome, and then the impact of a particular dietary pattern, the ketogenic diet, on the microbiota-gut-brain axis in epileptic patients. The investigation of the microbiota response to non-pharmacological therapies is an ever-expanding field with the potential to allow the design of increasingly accessible and successful intervention strategies.

Efficacy and safety of the endothelin-1 receptor antagonist macitentan in epicardial and microvascular vasospasm; a proof-of-concept study

BackgroundTreatment of patients diagnosed with angina due to epicardial or microvascular coronary artery spasm (CAS) is challenging because patients often remain symptomatic despite conventional pharmacological therapy. In this prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept study, we compared the efficacy and safety of macitentan, a potent inhibitor of the endothelin-1 receptor, to placebo in symptomatic patients with CAS despite background pharmacological treatment. MethodsPatients with CAS diagnosed by invasive spasm provocation testing with >3 anginal attacks per week despite pharmacological treatment were considered for participation. Participants received either 10 mg of macitentan or placebo daily for 28 days as add-on treatment. After a wash-out period patients were crossed over to the alternate treatment arm. The primary endpoint was the difference in anginal burden calculated as [1] the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1–10); and [2] the frequency of angina attacks * severity during medication use compared to the run-in phase. Results28 patients of whom 22 females (79%) and a mean age of 55.3 ± 7.6 completed the entire study protocol (epicardial CAS n = 19 (68), microvascular CAS n = 9 (32)). Change in both indices of anginal burden were not different during treatment with add-on macitentan as compared to add-on placebo (duration*severity: −9 [−134 78] vs −45 [−353 11], p = 0.136 and frequency*severity: −1.7 [−5.8 1.2] vs −1.8 [−6.2 0.3], p = 0.767). The occurrence and nature of self-reported adverse events were closely similar between the treatment phase with macitentan and placebo. ConclusionIn patients with angina due to epicardial or microvascular CAS despite background pharmacological treatment, 28 days of add-on treatment with the ET-1 receptor antagonist, macitentan 10 mg daily, did not reduce anginal burden compared to add-on treatment with placebo.Trial Registrationhttps://trialsearch.who.int/, Identifier: EUCTR2018-002623-42-NL. Registration date: 20 February 2019.

Therapeutic Potential of Hibiscus sabdariffa Linn. in Attenuating Cardiovascular Risk Factors.

Cardiovascular diseases (CVDs) represent a broad spectrum of diseases afflicting the heart and blood vessels and remain a major cause of death and disability worldwide. CVD progression is strongly associated with risk factors, including hypertension, hyperglycemia, dyslipidemia, oxidative stress, inflammation, fibrosis, and apoptosis. These risk factors lead to oxidative damage that results in various cardiovascular complications including endothelial dysfunctions, alterations in vascular integrity, the formation of atherosclerosis, as well as incorrigible cardiac remodeling. The use of conventional pharmacological therapy is one of the current preventive measures to control the development of CVDs. However, as undesirable side effects from drug use have become a recent issue, alternative treatment from natural products is being sought in medicinal plants and is gaining interest. Roselle (Hibiscus sabdariffa Linn.) has been reported to contain various bioactive compounds that exert anti-hyperlipidemia, anti-hyperglycemia, anti-hypertension, antioxidative, anti-inflammation, and anti-fibrosis effects. These properties of roselle, especially from its calyx, have relevance to its therapeutic and cardiovascular protection effects in humans. This review summarizes the findings of recent preclinical and clinical studies on roselle as a prophylactic and therapeutic agent in attenuating cardiovascular risk factors and associated mechanisms.

Living Cells and Cell-Derived Vesicles: A Trojan Horse Technique for Brain Delivery.

Brain diseases remain a significant global healthcare burden. Conventional pharmacological therapy for brain diseases encounters huge challenges because of the blood-brain barrier (BBB) limiting the delivery of therapeutics into the brain parenchyma. To address this issue, researchers have explored various types of drug delivery systems. Cells and cell derivatives have attracted increasing interest as "Trojan horse" delivery systems for brain diseases, owing to their superior biocompatibility, low immunogenicity, and BBB penetration properties. This review provided an overview of recent advancements in cell- and cell-derivative-based delivery systems for the diagnosis and treatment of brain diseases. Additionally, it discussed the challenges and potential solutions for clinical translation.

Suggested Integrative Approach for Hand Abscess with Cupping Therapy: a case study

A forty-three-year-old male patient was diagnosed with an acute abscess in the dorsum of the right hand. On the 5th day of conventional pharmacological therapy the patient was still suffering, and was referred to the Outpatient department (OPD) to evacuate and drain the abscess and treat the edema around the area with Hijama (wet cupping therapy, WCT). The hand abscess was successfully cured within a week using an integrative approach of wet cupping therapy together with conventional drug therapy.

Electroacupuncture activated local sympathetic noradrenergic signaling to relieve synovitis and referred pain behaviors in knee osteoarthritis rats.

Recent research has focused on the local control of articular inflammation through neuronal stimulation to avoid the systemic side effects of conventional pharmacological therapies. Electroacupuncture (EA) has been proven to be useful for inflammation suppressing and pain reduction in knee osteoarthritis (KOA) patients, yet its mechanism remains unclear. In the present study, the KOA model was established using the intra-articular injection of sodium monoiodoacetate (MIA) (1 mg/50 μL) into the knee cavity. EA was delivered at the ipsilateral ST36-GB34 acupoints. Hind paw weight-bearing and withdrawl thresholds were measured. On day 9, the histology, dep enrichment proteins, cytokines contents, immune cell population of the synovial membrane of the affected limbs were measured using HE staining, Masson staining, DIA quantitative proteomic analysis, flow cytometry, immunofluorescence staining, ELISA, and Western Blot. The ultrastructure of the saphenous nerve of the affected limb was observed using transmission electron microscopy on the 14th day after modeling. The result demonstrated that EA intervention during the midterm phase of the articular inflammation alleviated inflammatory pain behaviors and cartilage damage, but not during the early phase. Mid-term EA suppressed the levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 in the synovium on day 9 after MIA by elevating the level of sympathetic neurotransmitters Norepinephrine (NE) in the synovium but not systemic NE or systemic adrenaline. Selective blocking of the sympathetic function (6-OHDA) and β2-adrenergic receptor (ICI 118,551) prevented the anti-inflammatory effects of EA. EA-induced increment of the NE in the synovium inhibited the CXCL1-CXCR2 dependent overexpression of IL-6 in the synovial macrophages in a β2-adrenergic receptor (AR)-mediated manner. These results revealed that EA activated sympathetic noradrenergic signaling to control local inflammation in KOA rats and contributed to the development of novel therapeutic neurostimulation strategies for inflammatory diseases.

Discovery of Novel Thiazolidinedione-Derivatives with Multi-Modal Antidiabetic Activities In Vitro and In Silico.

Diabetes mellitus (DM) and related complications continue to exert a significant burden on health care systems globally. Although conventional pharmacological therapies are beneficial in the management of this metabolic condition, it is still necessary to seek novel potential molecules for its management. On this basis, we have synthesised and evaluated the anti-diabetic properties of four novel thiazolidinedione (TZD)-derivatives. The TZD derivatives were synthesised through the pharmacophore hybridisation strategy based on N-arylpyrrole and TZD. The resultant derivatives at different concentrations were screened against key enzymes of glucose metabolism and glucose utilisation in the liver (HEP-G2) cell line. Additionally, peroxisome proliferator-activated receptor-γ activation was performed through docking studies. Docking of these molecules against PPAR-γ predicted strong binding, similar to that of rosiglitazone. Hence, TZDD2 was able to increase glucose uptake in the liver cells as compared to the control. The enzymatic inhibition assays showed a relative inhibition activity; with all four derivatives exhibiting ≥ 50% inhibition activity in the α-amylase inhibition assay and a concentration dependent activity in the α-glucosidase inhibition assay. All four derivatives exhibited ≥30% inhibition in the aldose reductase inhibition assay, except TZDD1 at 10 µg/mL. Interestingly, TZDD3 showed a decreasing inhibition activity. In the dipeptidyl peptidase-4 inhibition assay, TZDD2 and TZDD4 exhibited ≥20% inhibition activity.

Outcomes of the butler neural mobilization technique and manual therapy for chronic low back pain in patients with lumbar radiculopathy: A cross-sectional comparative study

Surgeries were considered the only effective treatment method for patients suffering from chronic low back pain with lumbar radiculopathy for a while. However, in the contemporary world, it is not regarded as the primary treatment method until other conventional pharmacological and physical therapy interventions have not proven effective. Therefore, this study compares the outcomes in terms of pain relief and perceived level of mobility in patients with chronic low back pain with lumbar radiculopathy, regardless of whether the butler neural mobilization technique or manual therapy is used. This comparative cross-sectional study was conducted in Lahore, recruiting 100 patients by rendering a purposive sampling technique undergoing any treatment method mentioned above. Observations were recorded pre- and postintervention with a follow-up of 7 days to assess the response to both techniques using a questionnaire. Face-to-face interviews were conducted to assess pain levels using the Numeric Pain Rating Scale (NPRS) and Modified Oswestry Disability Questionnaire (MODQ). Descriptive statistics, chi-square test, Mann‒Whitney U test, independent t test, and the Wilcoxon signed-rank test were used to analyze the data. The medical characteristics of patients who had opted for manual therapy and butler neural mobilization were not different (p &gt; 0.05), except for the quality of pain (p &lt; 0.05). However, pre- and postintervention NPRS scores, pain intensity during the last 24 hours using NPRS scores, and MODQ scores were significantly different among the groups, indicating postintervention pain reduction for both groups comprising patients who had opted for manual therapy (p = 0.001) and butler neural mobilization technique (p = 0.001). Moreover, patients who had opted for either technique had improved their disability levels compared with the preintervention disability levels (p = 0.001). The study concluded that both techniques significantly reduce pain and disability levels, including butler neural mobilization and manual therapy, among patients suffering from chronic low back pain with lumbar radiculopathy.

Neuroprotection and Non-Invasive Brain Stimulation: Facts or Fiction?

Non-Invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS) and repetitive Magnetic Transcranial Stimulation (rTMS), are well-known non-pharmacological approaches to improve both motor and non-motor symptoms in patients with neurodegenerative disorders. Their use is of particular interest especially for the treatment of cognitive impairment in Alzheimer's Disease (AD), as well as axial disturbances in Parkinson's (PD), where conventional pharmacological therapies show very mild and short-lasting effects. However, their ability to interfere with disease progression over time is not well understood; recent evidence suggests that NIBS may have a neuroprotective effect, thus slowing disease progression and modulating the aggregation state of pathological proteins. In this narrative review, we gather current knowledge about neuroprotection and NIBS in neurodegenerative diseases (i.e., PD and AD), just mentioning the few results related to stroke. As further matter of debate, we discuss similarities and differences with Deep Brain Stimulation (DBS)-induced neuroprotective effects, and highlight possible future directions for ongoing clinical studies.