Diabetic Retinopathy - Pathophysiology to Treatment: A Review.

Diabetic retinopathy (DR) is a microvascular disease affecting the eyes of diabetic patients, and is the most prevalent complication of diabetes mellitus. Vision improvement is not possible in the majority of DR patients. Several studies have indicated that microvascular changes, inflammation, oxidative stress, and retinal neurodegeneration are involved in the pathogenesis of DR. Therefore, there is an urgent need for the development of new and effective treatment for DR. Understanding the molecular mechanisms involved in the pathogenesis of disease will pave a way for better treatment and management of DR. This article has emphasized the molecular pathogenesis and treatment of DR.

Exploring the Therapeutic Potential of Phytoconstituents for Addressing Neurodegenerative Disorders.

Neurodegenerative disorder is a serious condition that is caused by abnormal or no neurological function. Neurodegenerative disease is a major growing cause of mortality and morbidity worldwide, especially in the elderly. After World War Ⅱ, eugenics term was exterminated from medicines. Neurodegenerative disease is a genetically inherited disease. Lifestyle changes, environmental factors, and genetic modification, together or alone, are involved in the occurrence of this disorder. The major examples of neurodegenerative disorders are Alzheimer's and Parkinson's disease, in which apoptosis and necrosis are the two major death pathways for neurons. It has been determined from various studies that the etiology of the neurodegenerative disease involves the role of oxidative stress and anti-oxidant defence system, which are prime factors associated with the activation of signal transduction pathway that is responsible for the formation of synuclein in the brain and manifestation of toxic reactions in the form of functional abnormality, which ultimately leads to the dysfunction of neuronal pathway or cell. There has not been much success in the discovery of effective therapy to treat neurodegenerative diseases because the main cause of abnormal functioning or death of neurons is not well known. However, the use of natural products that are derived from plants has effective therapeutic potential against neurodegenerative disease. The natural compounds with medicinal properties to prevent neurological dysfunction are curcumin, wolfberry, ginseng, and Withania somnifera. The selection and use of natural compounds are based on their strong anti-inflammatory and anti-oxidant properties against neurodegenerative disease. Herbal products have active constituents that play an important role in the prevention of communication errors between neurons and neurotransmitters and their respective receptors in the brain, which influence their function. Considering this, natural products have great potential against neurodegenerative diseases. This article reviews the natural compounds used to treat neurodegenerative diseases and their mechanisms of action.

Recent Advances in the Prevention and Management of Monkeypox Viral Infection in Humans.

BACKGROUND: There have been several neglected infectious pathogens that have reemerged in the last few decades, including the monkeypox virus, a virus from the orthopoxviral genus that causes monkeypox and is transmitted between animals and humans. The human monkeypox outbreak has spread to several different countries. Because of the outbreak's unusually high case count and lack of connections to endemic nations, there are concerns that the monkeypox transmission pattern may have changed. OBJECTIVE: The current study aimed to provide recent advancements in the prevention and management of the monkeypox virus in humans. METHODOLOGY: We have highlighted recent advancements in the prevention and management of the monkeypox virus in humans in this work. RESULTS: For the treatment and prevention of monkeypox, new medications and vaccinations are being used, and more study is needed to understand the epidemiology, biology, and ecology of the virus in endemic regions and stop future global outbreaks. Vaccines available in the market for the treatment of viruses are JYNEOS and ACAM2000. Some of the antiviral drugs, such as tecovirimat, brincidofovir, cidofovir, trifluridine, and vaccinia immune globulin, are used for the treatment of the monkeypox virus. Some of the vaccines, such as NIOCH-14, Cidofovir, CMX-001, and ST-246, are currently in clinical trials. CONCLUSION: We have, herein, covered features of monkeypox viral biology that are important for risk assessment and getting ready for an outbreak of the monkeypox virus, with a focus on recent advances in knowledge of the virus's host range, evolutionary potential, and potential targets for neutralization.

Exploring multifunctional antioxidants as potential agents for management of neurological disorders.

Free radical or oxidative stress may be a fundamental mechanism underlying several human neurologic diseases. Therapy using free radical scavengers (antioxidants) has the potential to prevent, delay, or ameliorate many neurologic disorders. However, the biochemistry of oxidative pathobiology is complex, and optimum antioxidant therapeutic options may vary and need to be tailored to individual diseases. In vitro and animal model studies support the potential beneficial role of various antioxidant compounds in neurological disease. Antioxidants generally play an important role in reducing or preventing the cell damage and other changes which occur in the cells like mitochondrial dysfunction, DNA mutations, and lipid peroxidation in the cell membrane. Based on their mechanism of action, antioxidants can be used to treat various neurological disorders like Huntington's disease, Alzheimer's disease, and Parkinson's disease. Vitamin E has a scavenging action for reactive oxygen species (ROS) and also prevents the lipid peroxidation. Creatine generally reduces the mitochondrial dysfunction in Parkinson's disease (PD) patients. Various metal chelators are used in PD for the prevention of accumulation of the metals. Superoxidase dismutase (SOD), lipases, and proteases act as repair enzymes in patients with AD. Accordingly, the antioxidant defense system is found to be most useful for treating various neurological disorders.

Hidden pharmacological activities of valproic acid: A new insight.

Valproic acid (VPA) is an approved drug for managing epileptic seizures, bipolar disorders, and migraine. VPA has been shown to elevate the level of gamma-aminobutyric acid (GABA) in the brain through competitive inhibition of GABA transaminase, thus promoting the availability of synaptic GABA and facilitating GABA-mediated responses. VPA, which is a small chain of fatty acids, prevents histone deacetylases (HDACs). HDACs play a crucial role in chromatin remodeling and gene expression through posttranslational changes of chromatin-associated histones. Recent studies reported a possible effect of VPA against particular types of cancers. This effect was partially attributed to its role in regulating epigenetic modifications through the inhibition of HDACs, which affect the expression of genes associated with cell cycle control, cellular differentiation, and apoptosis. In this review, we summarize the current information on the actions of VPA in diseases such as diabetes mellitus, kidney disorders, neurodegenerative diseases, muscular dystrophy, and cardiovascular disorders.

Naturally Inspired Pyrimidines Analogues for Alzheimer's Disease.

Alzheimer's disease (AD) is a multifarious and developing neurodegenerative disorder. The treatment of AD is still a challenge and availability of drug therapy on the basis of symptoms is not up to the mark. In the context of existence, which is getting worse for the human brain, it is necessary to take care of all critical measures. The disease is caused due to multidirectional pathology of the body, which demands the multi-target-directed ligand (MTDL) approach. This gives hope for new drugs for AD, summarized here in with the pyrimidine based natural product inspired molecule as a lead. The review is sufficient in providing a list of chemical ingredients of the plant to cure AD and screen them against various potential targets of AD. The synthesis of a highly functionalized scaffold in one step in a single pot without isolating the intermediate is a challenging task. In few examples, we have highlighted the importance of this kind of reaction, generally known as multi-component reaction. Multi-component is a widely accepted technique by the drug discovery people due to its high atom economy. It reduces multi-step process to a one-step process, therefore the compounds library can be made in minimum time and cost. This review has highlighted the importance of multicomponent reactions by giving the example of active scaffolds of pyrimidine/fused pyrimidines. This would bring importance to the fast as well as smart synthesis of bio-relevant molecules.

To Compare the Level of Cystatin C in Type 2 Diabetes Mellitus with Obesity.

BACKGROUND: Cystatin C is a non-glycosylated basic protein that is produced and secreted at a constant rate by all nucleated cells. Cystatin C is a more reliable marker than the serum creatinine because it is less affected by external factors such as gender, race and muscle mass. However, the comparison of serum cystatin C level in type 2 diabetes mellitus is not well known in people with obesity. OBJECTIVES: To estimate the level of cystatin C in type 2 diabetes and that can be explained by the change in obesity. Thus, this current study aimed to determine and compare the level of cystatin C in type 2 DM with obesity and also correlate the cystatin C level with the quality of life in type 2 DM and obesity. MATERIAL AND METHODS: We have taken three groups: Group A containing type 2 DM, Group B containing obesity, and Group C containing type 2 DM with obesity. In all, 25 patients in each group were selected and analyzed for cystatin C. RESULTS: Cystatin C level was very high in type 2 DM with obesity group. The P value was 0.008 in type 2 DM with the obesity group and it has shown a highly significant correlation with BMI. In our study, we have also seen the positive correlation of cystatin C with BMI in Group B plain obese and Group C diabetes obese than Group A diabetes non-obese. We have seen in our study and found a poor correlation between HbA1c, RBS and cystatin C. CONCLUSION: The level of cystatin C is much higher in type 2 DM with obese patient as compared with type 2 DM and obese patients.

Cost-effective analysis of disease-modifying anti-rheumatic drugs in rheumatoid arthritis.

The main objective of the study was to perform the pharmacoeconomic analysis of synthetic disease-modifying anti-rheumatic drugs in rheumatoid arthritis patients. A prospective, observational study was conducted in 98 rheumatoid arthritis (RA) patients meeting 2010 Rheumatoid Arthritis Classification Criteria. Treatment-naive RA patients were initiated on synthetic disease-modifying anti-rheumatic drugs (DMARD/s) and followed up for 3 months. Average cost-effectiveness analysis was done by taking Health Assessment Questionnaire Disability Index (HAQ-DI) score as a measure of effectiveness. Out of the 98 RA patients, 15.30% were males and 84.69% females. 80.61% RA patients are seropositive. Majority of the study population patients (55%) were on combination of three synthetic DMARDs and almost a quarter (24.48%) were on combination of two synthetic DMARDs. The mean value of DAS 28 at baseline was 6.07 ± 1.33 and after 3 months treatment, the mean was 3.84 ± 1.11. The mean disability index measured by HAQ-DI was significantly reduced from 1.43 ± 0.71 to 0.81 ± 0.61, p < 0.001, after 3 months treatment. The direct medical cost of treatment of RA per month is 997.05 rupees. The average cost-effectiveness ratio of combination of synthetic DMARDs was 1533.92 rupees. Treatment of RA with synthetic DMARDs controls disease activity and improves disability with reasonable cost of treatment. The majority of the direct medical cost is attributable to cost of medicine and laboratory investigation. Use of quality generic drugs and an early diagnosis would minimize the economic burden on the patient.

Predictors of endothelial dysfunction and atherosclerosis in rheumatoid arthritis in Indian population.

OBJECTIVE: Cardiovascular (CV) disease is leading cause of mortality in rheumatoid arthritis (RA). Dysfunction of the vascular endothelium is a hallmark of most conditions that are associated with atherosclerosis and is therefore an early feature in atherogenesis. Biomarkers for rapid evolution of CV complications would be highly desirable for risk stratification. Finally, predictive biomarkers for cardiovascular risk would allow tailoring therapy to the individual. We assessed endothelial function and atherosclerosis utilizing carotid intima-media thickness (CIMT) in RA in context of clinical and laboratory markers in Indian RA population. METHODS: We performed a prospective study of 35 consecutive RA patients and 25 age- and sex matched healthy controls. Patients with traditional CV risk factors were excluded. Flow mediated dilatation (FMD) as measures of endothelial function and CIMT as measures of atherosclerosis were assessed. Disease-specific measures, inflammatory measures, serum cytokines, serum nitrite, lipids and endothelial progenitor cells (EPCs) were estimated. RESULTS: FMD was significantly lower in RA (6.53%±1.81%) compared to controls (10.77%±0.53%; p<0.001). CIMT (mm) was significantly increased in RA (0.62±0.17) vs. controls (0.043±0.07; p=0.003). In RA patients, FMD% inversely correlated with CIMT, CRP, DAS-28, TNF-α, serum nitrite and positively correlated with EPC. CIMT correlated with age, DAS-28, IL-6, HDL, LDL, and inversely correlated with EPC. CONCLUSIONS: In the present study, FMD and CIMT were impaired in RA, indicating endothelial dysfunction and accelerated atherosclerosis respectively. CRP, TNF-α, serum nitrite, DAS-28 and depleted EPC population predicted endothelial dysfunction. Age, IL-6, HDL, LDL and depleted EPC population predicted accelerated atherosclerosis.

Endothelial Progenitor Cells as a Marker of Endothelial Dysfunction and Atherosclerosis in Ankylosing Spondylitis: A Cross-Sectional Study.

Endothelial progenitor cells (EPCs) have reparative potential in overcoming the endothelial dysfunction and reducing cardiovascular risk. EPC depletion has been demonstrated in the setting of established atherosclerotic diseases. We evaluated whether reduced EPCs population are associated with endothelial dysfunction, subclinical atherosclerosis, and inflammatory markers in ankylosing spondylitis (AS) patients without any known traditional cardiovascular risk factor. We performed a cross-sectional study of 30 consecutive AS patients and 25 age- and sex-matched healthy controls. Patients with traditional cardiovascular risk factors were excluded. Circulating EPCs (CD34+/CD133+) were quantified by flow cytometry. The assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and ultrasound assessment of carotid intima-media thickness (CIMT) was measured in both the groups. EPCs cells were significantly (0.020 ± 0.001 vs. 0.040 ± 0.010%, p < 0.001) reduced in patients with AS compared with healthy controls. Endothelial function (7.35 ± 2.54 vs. 10.27 ± 1.73, p = 0.002), CIMT (0.63 ± 0.01 vs. 0.35 ± 0.02, p < 0.001), and inflammatory markers were also significantly (p < 0.01) altered as compared with controls. EPCs inversely correlated with tumor necrosis factor (TNF)-α and C-reactive protein (CRP) and positively correlated with endothelial function. Present study results demonstrate depleted EPC population in AS patients compared with controls. Increased level of CRP and TNF-α appears to play a key role in EPC depletion and the latter contributes to endothelial dysfunction and atherosclerosis in AS. EPC population would, therefore, represent an attractive measure of endothelial dysfunction and accelerated atherosclerosis disease associated with AS.

Predictors of autonomic neuropathy in rheumatoid arthritis.

OBJECTIVE: Autonomic dysfunction occurs in rheumatoid arthritis (RA). However, the association between the autonomic dysfunction and inflammation has not been investigated in RA. We investigated the relationship between inflammation and ANS function in RA. METHODS: In this cross-sectional study, 25 RA patients and 25 age and sex-matched healthy controls were recruited. Autonomic function assessed by five cardiovascular reflex tests according to Ewing. Parasympathetic dysfunction established by applying three tests: heart rate response to deep breath (HRD) and standing (HRS) and Valsalva tests. Sympathetic dysfunction examined by applying two tests: BP response to standing and handgrip test. Peripheral sympathetic autonomic function assessed by Sudoscan through measurement of electrochemical skin conductance of hands and feet. Sudoscan investigates the sweat gland activity and used as a surrogate to study the damage of sympathetic sudomotor nerves in neuropathy. It is an indirect assessment tool of sudomotor function. Disease-specific and inflammatory measures (DAS 28, ESR, CRP, TNF-α, IL-6 and IL-1) were determined. RESULTS: RA patients had significantly impaired HRD, HRS, BP response to hand grip and sudomotor function as compared to healthy controls. Pro-inflammatory cytokines were significantly higher in RA as compared to healthy controls (p<0.05). DAS 28 significantly correlated with HRD in RA. ESR significantly correlated with HRD and HRS. TNF-α significantly correlated with HRD, HRS, BP response to standing and sudomotor function. Significant correlation was found between IL-6 and HRS. Seropositive patients had more pronounced CAN and sudomotor dysfunction. CONCLUSION: Autonomic dysfunction in RA is related to disease activity, seropositivity and pro-inflammatory cytokines.

Disease-modifying antirheumatic drugs improve cardiovascular autonomic neuropathy in psoriatic arthritis.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a significant risk predictor for sudden cardiac death in autoimmune rheumatic diseases. As yet, there is no therapeutic treatment of CAN in psoriatic arthritis (PsA). Even now, the impact of the most commonly employed disease-modifying antirheumatic drug (DMARD) therapy on CAN in PsA is not known. Hence, we investigated the impact of DMARDs on CAN in PsA. METHODS: In this prospective, cross-sectional study, 20 patients of PsA and 20 age- and sex-matched healthy controls were recruited. CAN was diagnosed by applying the five cardiovascular reflex tests according to Ewing. Parasympathetic dysfunction was established by performing three tests: heart-rate response to deep breathing, standing, and Valsalva tests. Sympathetic dysfunction was examined by applying two tests: blood pressure response to standing, and handgrip tests. Disease severity was assessed by the 28-joint-count disease activity score (DAS-28) and the disease activity score in psoriatic arthritis (DAPSA). RESULTS: Cardiovascular reflex tests were impaired significantly among the PsA patients compared with well-matched healthy subjects (p < 0.05). Parasympathetic dysfunction was more prominent than sympathetic dysfunction. After 12 weeks treatment, parasympathetic dysfunction (heart rate response to deep breath and standing) significantly (p < 0.05) improved in patients with PsA, while there was no significant improvement in sympathetic function. CONCLUSION: These study results suggests parasympathetic autonomic dysfunction is more prominent than sympathetic dysfunction in PsA. Synthetic DMARDs improved parasympathetic dysfunction in PsA.

Interleukin-6 blockade improves autonomic dysfunction in rheumatoid arthritis.

Autonomic nervous system (ANS) involvement in rheumatoid arthritis (RA) is well recognised and contributes to arrhythmia and sudden death. However, there is no study documented the therapeutic efficacy on autonomic neuropathy (AN) in RA. This is the first reported observation of improvement in AN with interleukin-6 (IL-6) blockade with tocilizumab in RA. We report a case of 61-year old female with seropositive RA with severe disease activity, investigated for autonomic neuropathy. A battery of non invasive tests was used for accurate assessment of AN function based on assessment of peripheral sympathetic autonomic function and cardiovascular reflex tests. Tocilizumab 8 mg/kg intravenous infusion at weeks 0, 4 and 8 was added to her treatment regimen. Cardiovascular autonomic function tests at baseline showed marked abnormalities of parasympathetic cardiovascular reflexes. After the first dose of tocilizumab there was a rapid improvement with normalization of parasympathetic autonomic activity with subsequent doses. IL-6 blockade with tocilizumab seems to have the potential to improve the vagus nerve mediated parasympathetic neuropathy and hence has the potential to restore cholinergic anti-inflammatory pathway.

Disease-modifying anti-rheumatic drugs improve autonomic neuropathy in arthritis: DIANA study.

Autonomic neuropathy (AN) is a risk predictor for sudden cardiac death in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, the impact of most commonly employed disease-modifying anti-rheumatic drug (DMARD) therapy on autonomic neuropathy in rheumatic diseases is not known. Hence, we investigated the efficacy of DMARDs on autonomic neuropathy in RA and AS. We performed autonomic function assessment in 60 patients in this open-label, 12-week pilot study including 42 patients with RA, 18 with AS, and 30 aged-matched healthy subjects. The methodology included assessment of cardiovascular autonomic reflex tests according to Ewing. Parasympathetic dysfunction was established by performing three tests: heart rate response to deep breathing, standing, and Valsalva tests. Sympathetic dysfunction was examined by applying two tests: blood pressure response to standing and handgrip tests. Sudomotor function was assessed by Sudoscan. Cardiovascular reflex tests were impaired significantly among the patients as compared to healthy subjects (p < 0.05). Autonomic neuropathy was more pronounced in biologic-naive RA and AS patients. After treatment with combination synthetic DMARDs, parasympathetic, and sudomotor dysfunction significantly (p < 0.05) improved in RA and AS. Biologic DMARDs significantly improved parasympathetic, sympathetic and peripheral sympathetic autonomic neuropathy (p < 0.05) in biologic-naive RA and AS patients. In conclusion, synthetic DMARDs improved parasympathetic and sudomotor dysfunction in both DMARD-naive RA and AS patients. However, biologic DMARDs improved parasympathetic, sympathetic and sudomotor dysfunction to a greater extent than synthetic DMARDs in both RA and AS patients.

Endothelial progenitor cell biology in ankylosing spondylitis.

AIM: Endothelial progenitor cells (EPCs) are unique populations which have reparative potential in overcoming endothelial damage and reducing cardiovascular risk. Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular morbidity and mortality. The aim of this study was to investigate the endothelial progenitor cell population in AS patients and its potential relationships with disease variables. METHODS: Endothelial progenitor cells were measured in peripheral blood samples from 20 AS and 20 healthy controls by flow cytometry on the basis of CD34 and CD133 expression. Disease activity was evaluated by using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI). RESULTS: EPCs were depleted in AS patients as compared to healthy controls (CD34(+) /CD133(+) : 0.027 ± 0.010% vs. 0.044 ± 0.011%, P < 0.001). EPC depletions were significantly associated with disease duration (r = -0.52, P = 0.01), BASDAI (r = -0.45, P = 0.04) and C-reactive protein (r = -0.5, P = 0.01). CONCLUSION: This is the first study to demonstrate endothelial progenitor cell depletion in AS patients. EPC depletions inversely correlate with disease duration, disease activity and inflammation, suggesting the pivotal role of inflammation in depletion of EPCs. EPC would possibly also serve as a therapeutic target for preventing cardiovascular disease in AS.

Predictors of Atherosclerosis in Ankylosing Spondylitis.

OBJECTIVE: Accelerated atherosclerosis associated with an enhanced inflammatory state, which characterizes ankylosing spondylitis (AS), is the leading cause of increased cardiovascular risk. The objective of this study was to assess carotid intima-media thickness (CIMT) as a surrogate for subclinical atherosclerosis in AS patients and its possible correlation with disease-related clinical parameters. METHODS: We performed a prospective study of 30 consecutive patients meeting modified New York criteria for AS compared to 25 controls matched for age and sex. Patients with traditional CV risk factors were excluded. Disease-specific measures and inflammatory measures (ESR, CRP, TNF-α, IL-6 and IL-1) were determined. CIMT was measured in the right common carotid artery using high-resolution B-mode ultrasound. RESULTS: AS patients exhibited increased CIMT compared to matched healthy controls (0.62 ± 0.12 vs. 0.53 ± 0.09 mm). CIMT was positively correlated with age, disease duration, disease activity (BASDAI and ASDAS) and the inflammatory measures ESR (r = 0.45, P = 0.11) and TNF-α (r = 0.62, P < 0.001). CIMT did not correlate with the BMI, BASFI, IL-6, IL-1 or cholesterol levels. CONCLUSIONS: This study shows increased CIMT in AS patients without traditional cardiovascular risk factors compared to healthy controls. An increase in age, disease duration, disease activity (BASDAI and ASDAS), biomarkers of inflammation (ESR and CRP) and TNF-α may predict the occurrence of accelerated atherosclerosis in AS.

Minocycline improves peripheral and autonomic neuropathy in type 2 diabetes: MIND study.

Diabetic peripheral neuropathy and diabetic autonomic neuropathy are serious and common complications of diabetes associated with increased risk of mortality and cardiovascular disease. We sought to evaluate the safety and efficacy of minocycline in type 2 diabetic patients with diabetic peripheral and autonomic neuropathy. In a randomized placebo controlled study, 50 outpatients were randomly assigned to receive 100 mg minocycline or placebo. Outcome measures included the vibration perception threshold (VPT), Leeds assessment of neuropathic symptoms and signs (LANSS), Pain Disability Index (PDI), Visual Analog Scale (VAS), beck depression inventory (BDI), health assessment questionnaire (HAQ) and autonomic neuropathy, assessed by cardiovascular reflex tests according to Ewing and peripheral sympathetic autonomic function was assessed by FDA approved Sudoscan. At baseline there were no significant differences between demographic variables and the neuropathy variables in the minocycline and placebo groups. After treatment, VPT significantly improved in the minocycline group as compared to the placebo group. Mean posttreatment scores on the LANSS, PDI and HAQ were significantly lower in the minocycline group compared with the placebo group. However, BDI and VAS significantly (p = 0.01) improved in both minocycline and placebo groups (Table 2). After treatment with minocycline, heart rate (HR) response to standing significantly improved, while there was a borderline significance toward a reduction in HR response to deep breath. These finding indicate that 6-week oral treatment with minocycline is safe, well tolerated and significantly improves peripheral and autonomic neuropathy in type 2 diabetic patients.

Autonomic dysfunction in psoriatic arthritis.

Autonomic nervous system (ANS) involvement has been studied in systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjogren's syndrome, and ankylosing spondylitis but still has not been studied in psoriatic arthritis (PsA). The aim of this study was to investigate the prevalence and the nature of autonomic neuropathy in patients with PsA. Sixteen patients of PsA and 15 age and sex matched control subjects were studied prospectively using a battery of noninvasive tests. Cardiovascular autonomic neuropathy (CAN) was diagnosed by applying four cardiovascular reflex tests, and peripheral sympathetic autonomic function was assessed by Sudoscan. Patients with PsA had significantly higher heart rate response to standing (p = 0.01), blood pressure response to standing (p = 0.02), and Sudoscan (p = 0.01) when compared with healthy controls. Fifty percent (n = 8) of the patients with PsA had at least two or more abnormal CAN parasympathetic dysfunction; of these, 18.75% (n = 3) of the patients had abnormal parasympathetic and sympathetic dysfunction, 68.7% (n = 11) and 25% (n = 4) of the patients had at least one abnormal parasympathetic and sympathetic parameters, respectively, and 37.5% (n = 6) of the patients had moderate sudomotor dysfunction. About 18.7% (n = 3) of our parasympathetic dysfunction patients had autonomic symptoms. None of healthy volunteers had abnormal ANS dysfunction. Heart rate response significantly correlated with erythrocyte sedimentation rate (p < 0.05) and C-reactive protein (p < 0.05) levels. In conclusion, cardiovascular autonomic and peripheral sympathetic neuropathy occurs in PsA. Parasympathetic function is more commonly found to be abnormal than sympathetic function. There is no correlation of peripheral sympathetic dysfunction with cardiovascular autonomic neuropathy.

Spironolactone improves endothelial dysfunction in ankylosing spondylitis.

Chronic inflammation in ankylosing spondylitis (AS) is associated with vascular endothelial dysfunction which leads to accelerated atherosclerosis. Accelerated atherosclerosis contributes to premature cardiovascular disease and increased cardiovascular mortality in AS. Spironolactone inhibits the production of proinflammatory cytokines and improves endothelial dysfunction in rheumatoid arthritis. This study aimed to determine the effect of spironolactone in antitumor necrosis factor (TNF)-naive AS patients. Twenty anti-TNF-naive AS patients (M/F = 15/5) with high disease activity (Bath ankylosing spondylitis disease activity index, BASDAI >4) despite treatment with stable doses of conventional disease-modifying antirheumatic drugs were investigated. Inflammatory disease activity (BASDAI and Bath ankylosing spondylitis functional index (BASFI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels), serum nitrite concentration, and endothelium-dependent and -independent vasodilatation of the brachial artery were measured at baseline and after 12 weeks of therapy with oral spironolactone 2 mg/kg/day. Ten healthy subjects matched for age and sex acted as the control. Flow-mediated dilation (FMD) in AS patients at baseline was significantly impaired compared with healthy control group (p < 0.001). After treatment, FMD improved from 11.3 ± 1.70 to 24.69 ± 2.34% (p < 0.001); nitrite concentration reduced from 7.9 ± 0.28 to 4.79 ± 0.19 µmol/L (p < 0.001); ESR from 33.8 ± 4.38 to 15.13 ± 1.30 mm in the first hour, (p < 0.001); and CRP level from 22.39 ± 3.80 to 6.3 ± 1.29 mg/dL, (p < 0.001). BASDAI and BASFI also reduced significantly (p < 0.001). The study suggests that in AS endothelial dysfunction is a part of the disease process. This is the first study to show that treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity in AS.