An update on new-age potential biomarkers for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that deals with dopaminergic deficiency in Substantia nigra pars compact (SNpc) region of the brain. Dopaminergic deficiency manifests into motor dysfunction. Alpha-synuclein protein aggregation is the source for inception of the pathology. Motor symptoms include rigidity, akinesia, tremor and gait dysfunction. Pre-motor symptoms are also seen in early stage of the disease; however, they are not distinguishable. Lack of early diagnosis in PD pathology poses a major challenge for development of disease modifying therapeutics. Substantial neuronal loss has already been occurred before the clinical manifestations appear and hence, it becomes impossible to halt the disease progression. Current diagnostics are majorly based on the clinical symptoms and thus fail to detect early progression of the disease. Thus, there is need for early diagnosis of PD, for detection of the disease at its inception. This will facilitate the effective use of therapies that halt the progression and will make remission possible. Many novel biomarkers are being developed that include blood-based biomarker, CSF biomarker. Other than that, there are non-invasive techniques that can detect biomarkers. We aim to discuss potential role of these new age biomarkers and their association with PD pathogenesis in this review.

Uncovering Novel Therapeutic Targets for Parkinson's Disease.

Parkinson's disease (PD) is the second most prevailing progressive disorder leading to neurodegeneration, typically in people above 65 years of age. Motor clinical manifestations of PD appear in a much later stage and include rigidity, tremors, akinesia, and gait dysfunction. There are also nonmotor symptoms like GI and olfactory dysfunction. However, they cannot be considered for diagnosis of the disease, as they are unspecific. PD pathogenesis is mainly characterized by deposits of inclusion bodies on dopaminergic (DA) neurons in substantia nigra pars compacta region (SNpc) of the brain. The major component of these inclusion bodies, are α-synuclein aggregates. α-Synuclein undergoes misfolding and oligomerization to form aggregates and fibrils. These aggregates gradually propagate PD pathology. Other prominent features of this pathological development include mitochondrial dysfunction, neuroinflammation, oxidative stress, and impaired autophagy. These all contribute to neuronal degeneration. Besides this, there are many underlying factors which influence these processes. These factors comprise molecular proteins and signaling cascades. In this review, we have listed out underexplored molecular targets that may aid in development of neoteric and advanced therapeutics.

Chlorogenic Acid: a Polyphenol from Coffee Rendered Neuroprotection Against Rotenone-Induced Parkinson's Disease by GLP-1 Secretion.

Parkinson's disease (PD) is a chronic motor disorder, characterized by progressive loss of dopaminergic neurons. Numerous studies suggest that glucagon-like peptide-1 (GLP-1) secretagogue has a neuroprotective role in PD models. The present study evaluated potential of coffee bioactive compounds in terms of their ability to bind GPR-40/43 and tested the neuroprotective effect of best candidate on rotenone-induced PD mice acting via GLP-1 release. In silico molecular docking followed by binding free energy calculation revealed that chlorogenic acid (CGA) has a strong binding affinity for GPR-40/43 in comparison to other bioactive polyphenols. Molecular dynamics simulation studies revealed stable nature of GPR40-CGA and GPR43-CGA interaction and also provided information about the amino acid residues involved in binding. Subsequently, in vitro studies demonstrated that CGA-induced secretion of GLP-1 via enhancing cAMP levels in GLUTag cells. Furthermore, in vivo experiments utilizing rotenone-induced mouse model of PD revealed a significant rise in plasma GLP-1 after CGA administration (50 mg/kg, orally for 13 weeks) with concomitant increase in colonic GPR-40 and GPR-43 mRNA expression. CGA treatment also prevented rotenone-induced motor and cognitive impairments and significantly restored the rotenone-induced oxidative stress. Meanwhile, western blot results confirmed that CGA treatment downregulated rotenone-induced phosphorylated alpha-synuclein levels by upregulating PI3K/AKT signaling and inactivating GSK-3ß through the release of GLP-1. CGA treatment ameliorated rotenone-induced dopaminergic nerve degeneration and alpha-synuclein accumulation in substantia nigra and augmented mean density of dopaminergic nerve fibers in striatum. These findings demonstrated novel biological function of CGA as a GLP-1 secretagogue. An increase in endogenous GLP-1 may render neuroprotection against a rotenone mouse model of PD and has the potential to be used as a neuroprotective agent in management of PD.

Deciphering Intertwined Molecular Pathways Underlying Metabolic Syndrome Leading to Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that gradually develops over time in a progressive manner. The main culprit behind the disease pathology is dopaminergic deficiency in Substantia nigra Pars Compacta (SNpc) due to neuronal degeneration. However, there are other factors that are not only associated with it but also somehow responsible for inception of pathology. Metabolic syndrome is one such risk factor for PD. Metabolic syndrome is a cluster of diseases mainly including diabetes, hypertension, obesity, and hyperlipidemia which pose a risk for developing cardiovascular disorders. All of these disorders have their own pathological pathways that intertwine with PD pathology. This leads to alpha-synuclein aggregation, neuroinflammation, mitochondrial dysfunction, and oxidative stress which are facets in initiating PD pathology. Although few reports are available, this area is underexplored and has contradictory views. Hence, further studies are needed in order to establish a definite relationship between PD and metabolic syndrome. In this review, we aim to elucidate the molecular mechanisms to confirm the association between them and pave the way for potential repurposing of therapies.

Immunization in end-stage renal disease: opportunity to improve outcomes.

Infection is the second most common cause of death in patients with end-stage renal disease (ESRD), following cardiovascular causes. Immunization is a fairly simple, but underutilized, strategy for prevention of infectious morbidity and mortality in patients with kidney failure. It is imperative for nephrologists and primary care providers to have an understanding of immunization as an essential component of preventive healthcare measures in this high-risk population. Patients with ESRD represent a unique population due to their immunosuppressed state, dialysis-related exposures and suboptimal response to routine vaccines. While the Advisory Committee on Immunization Practices (ACIP) provides guidelines for vaccination of patients with renal disease against Hepatitis B, influenza and pneumococcal disease, the data on immunization against other commonly preventable infectious diseases are lacking. This article reviews the recent evidence on immunization in the ESRD population and synthesizes the related implications for maximizing prevention of infectious diseases in this high-risk population.

Effect of yoga practices on pulmonary function tests including transfer factor of lung for carbon monoxide (TLCO) in asthma patients.

Prana is the energy, when the self-energizing force embraces the body with extension and expansion and control, it is pranayama. It may affect the milieu at the bronchioles and the alveoli particularly at the alveolo-capillary membrane to facilitate diffusion and transport of gases. It may also increase oxygenation at tissue level. Aim of our study is to compare pulmonary functions and diffusion capacity in patients of bronchial asthma before and after yogic intervention of 2 months. Sixty stable asthmatic-patients were randomized into two groups i.e group 1 (Yoga training group) and group 2 (control group). Each group included thirty patients. Lung functions were recorded on all patients at baseline, and then after two months. Group 1 subjects showed a statistically significant improvement (P<0.001) in Transfer factor of the lung for carbon monoxide (TLCO), forced vital capacity (FVC), forced expiratory volume in 1st sec (FEV1), peak expiratory flow rate (PEFR), maximum voluntary ventilation (MVV) and slow vital capacity (SVC) after yoga practice. Quality of life also increased significantly. It was concluded that pranayama & yoga breathing and stretching postures are used to increase respiratory stamina, relax the chest muscles, expand the lungs, raise energy levels, and calm the body.

Study of the effect of yoga training on diffusion capacity in chronic obstructive pulmonary disease patients: A controlled trial.

BACKGROUND: Patients of chronic obstructive pulmonary disease (COPD) are at high risk for depression and anxiety. Yoga techniques are suited for promoting relaxation, psycho-emotional stability and exercise tolerance. Studies showing the effect of yoga in diffusion capacity are not available; hence this study was planned. MATERIALS AND METHODS: The study was conducted on 60 diagnosed stable mild-to-moderate COPD patients in the age group of 30-60 years, of either sex, in the department of physiology. Patients were taken from Guru Teg Bahadur Hospital, Delhi and divided into two groups: Control and the yoga group. Both the groups were on conventional drug therapy. Subjects from the Yoga group was called to cardiopulmonary laboratory daily for 21 days and then weekly for the compliance. Yoga instructor taught them the technique of pranayama and various postures every day. They practiced yoga at home for 2 months for 45 min in the mornings. Diffusion capacity was recorded by using computerized Medisoft instrument (HYPAIR compact), in both the groups before and after 2 months. RESULTS: Statistical analysis showed significant improvement in TLCO of the yoga group. Transfer factor of lung for carbon monoxide i.e. TLCO in mild COPD increased from 17.61 ± 4.55 to 19.08 ± 5.09 ml/mmHg/min, and in moderate COPD it increased from 14.99 ± 4.02 to17.35 ± 3.97 ml/mmHg/min. CONCLUSION: It was concluded that yogic breathing exercises improve diffusion capacity. They are beneficial to COPD patients and they can be used as an adjunct therapy with the conventional medical therapy.

Health-related quality of life in hypertension, chronic kidney disease, and coexistent chronic health conditions.

With the increasing prevalence of hypertension, there has been a growing interest in understanding the health-related quality of life (HRQOL) of patients with hypertension. Although hypertension is often perceived as asymptomatic, it is associated with impaired HRQOL because of complications or comorbidities, awareness of the diagnosis, and adverse effects from antihypertensive medications. This article focuses on the literature published since 2000, on HRQOL in elderly hypertensive individuals as well as hypertensives with co-existent diseases, including chronic kidney disease, cardiovascular disease, and diabetes mellitus. Most of the studies found that hypertensive individuals with co-existent co-morbidities tend to have lower HRQOL than those with hypertension alone, and identified the number of co-morbid illnesses as an independent determinant of HRQOL. The most pronounced effect was noted in the physical function domains of HRQOL. Studies have also examined the effects on HRQOL of specific classes of antihypertensive drugs without specific demonstration of superiority of one drug class over another in terms of HRQOL measures. Although there is evidence in favor of angiotensin-converting enzyme-inhibition for improving renal and cardiovascular outcomes in hypertensive patients, its role in ameliorating HRQOL outcomes remains to be established.

Health-related quality of life outcomes in chronic kidney disease.

PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) endure compromised health-related quality of life (HRQOL). Although the link between HRQOL and increased mortality in patients with end-stage renal disease (ESRD) is well documented, less is known about the relationship between CKD and HRQOL. This article reviews the recent evidence on HRQOL, its correlates and proposed intervention strategies to improve HRQOL in CKD. RECENT FINDINGS: A growing body of literature indicates that various comorbid conditions related to CKD play a substantial role in impaired HRQOL in CKD. Hypertension, both a cause and complication of CKD, negatively affects HRQOL due to associated comorbidities, side effects from antihypertensive medications and awareness of the diagnosis. Anemia has been associated with HRQOL, but concerns about the safety of erythropoietin-stimulating agents (ESAs) have led to more conservative anemia treatment. Frailty, symptom burden and depression are also major contributory factors to HRQOL in CKD. SUMMARY: Certain determinants of HRQOL in CKD, namely anemia and depression, are treatable. Early identification and correction may improve overall well being of patients. Clinical trials are required to demonstrate whether treatment interventions benefit HRQOL in this high-risk population. Furthermore, whether integration of HRQOL assessment into routine clinical practice will improve HRQOL outcomes remains to be determined.

Secondary hemicrania continua: Case reports and a literature review.

Hemicrania continua (HC) is an indomethacin responsive primary headache disorder. Secondary or symptomatic HC is associated with another neurological or non-neurological disease. We report three patients with secondary HC. We also review the literature to identify the clinical predictors of an underlying disease entity. Intracranial structural lesion, head and neck vessel pathology, and carcinoma lung should be suspected in every patient. The factors that may suggest a secondary pathology are: elderly age, male sex, smoking habit, constitutional symptoms, symptoms related to respiratory system, frequent and short-lived exacerbation, nocturnal exacerbation, HC evolving from remitting form, recent neck and/or head trauma, miosis, elevated ESR, and fading effect of indomethacin. We recommend MRI brain in all the patients presenting with HC or HC like headache. Angiography and CT chest are two other investigations that may be supplemented in patients with high risk for head/neck vessel pathology and carcinoma lung.