Integrative Treatment of Hypertension: A Clinical and Mechanistic Approach

Risk Factor Management in Atrial Fibrillation
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It sites a solid-state pressure sensor approximately 20 mm into the brain parenchyma, usually within the right frontal lobe. Of note, the UK driving regulations allow resumption of driving 1 week after insertion in patients without complications. The device provides a high degree of accuracy with low drift [36].

The device samples at 5 Hz, considerably lower than the wired and Miethke systems, although this is sufficient for waveform analysis [36,38]. The device is capable of long-term recordings for up to 1 week with the present hardware and can be worn by an ambulant patient out with the hospital environment Fig. Telemetric ICP monitors have an evolving role in diagnosis and monitoring of several conditions.

In IIH, particular roles could include evaluating whether neurosurgical shunt placement is advised in a deteriorating patient developing fulminant disease. Furthermore, it is useful in evaluating whether pressure is pathologically elevated in those with minimal ocular features and in shunted patients. ICP telemetry may also facilitate the differentiation between raised pressure headaches and migrainous headaches [39].

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Acetazolamide is the longest established treatment for IIH. There is, therefore, an unmet need for novel therapeutic strategies in IIH Fig. There are currently no novel drugs targeting the underlying pathogenesis driving IIH, which remains elusive. This amplifies local glucocorticoid activity independent of systemic cortisol. Inhibitors have been developed, including AZD, originally as potential therapies for diabetes mellitus type 2 and the metabolic syndrome.

Conversely systemic administration of glucocorticoids has been found to precipitate intracranial hypertension [50]. It recently completed recruitment and is expected to report in The incretin glucagon-like peptide 1 GLP-1 is a gut peptide secreted by the distal small intestine in response to food intake [52].

GLP-1 stimulates glucose-dependant insulin secretion and inhibits glucagon release, lowering blood glucose only in the presence of insulin and not resulting in hypoglycaemia [53]. GLP-1 is also synthesized in neurons of the nucleus tractus solaris that project to the hypothalamus [54] and promotes satiety and weight loss [55]. GLP-1 analogues have a clinical role in the management of type 2 diabetes mellitus, as well as for weight loss in obesity. Several GLP-1 agonists have been developed and are now licensed drugs [56].

These include exenatide twice daily, exenatide once weekly, liraglutide, lixisenatide, albiglutide, dulaglutide and most recently semaglutide. Currently, only liraglutide is licensed for weight loss in obesity.

ROLE OF GLUTATHIONE METABOLISM AND GLUTATHIONE-RELATED ANTIOXIDANT DEFENSE SYSTEMS IN HYPERTENSION

They vary in structure and pharmacology, ability to penetrate the blood—brain barrier BBB as evidenced by CNS effects. Importantly, the choroid plexus epithelium lies outside the BBB [57]. Choroid plexus epithelial cell function is inverted compared with renal proximal tubule but with an analogous fluid transport mechanism [59] , and as such GLP-1R was investigated as a potential target for conditions with raised ICP. Importantly exendin-4 reduced ICP in conscious rats at clinically relevant doses.

The action was blocked by intraventricular administration of the GLP-1R antagonist exendin , suggesting the effect is mediated by the GLP-1R in the brain. The incidence of IIH is increasing along with global rates of obesity, a key pathological factor, making IIH research and management increasingly important.

The first consensus guidelines for the management of IIH have now been published guiding the clinical management of this condition.

Looking to the future, there are several new avenues of clinical therapeutics based on reducing CSF secretion, with GLP-1 receptor agonists appearing promising as they also significantly reduce weight. Advances in OCT technology will continue to improve our diagnosis and monitoring of papilloedema, and may provide unique biomarkers. Contributor Statement: All authors have read and approved the final manuscript.

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Papers of particular interest, published within the annual period of review, have been highlighted as:. Consensus-based statements founded by a specialist interest group that included patients, allied health professionals, neurologists, neuroophthalmologists, neurosurgeons, neuroradiologists, and informed by multiple surveys of practice.

Up-to-date review of our understanding of headache in IIH. Presents the latest literature phenotyping the IIH headache as migraine, and highlighting the issue of medication of overuse headache in the IIH cohort. It reported the use of acetazolamide with a low-sodium weight-reduction diet compared with diet alone resulted in modest improvement in visual field function in patients with mild visual loss. The IIHTT also reported improved quality-of-life outcomes at 6 months with acetazolamide and diet group compared with diet alone.

A narrative review of the technology and methods in OCT angiography. Key advantages over Fundus Fluorescein Angiography are highlighted. It gives a practical guide to performing and reporting FFAs, highlighting key features that distinguish retinal lesions. Key article defining the evidence of existing drugs used in IIH and their mechanisms of action with subsequent evaluation at clinically relevant doses in vivo.

Article outlining the mechanistic basis for a potential new class of ICP-modulating therapy. You may be trying to access this site from a secured browser on the server. Please enable scripts and reload this page. Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent.

For more information, please refer to our Privacy Policy. Subscribe to eTOC. Advanced Search. Toggle navigation. Subscribe Register Login. Your Name: optional. Your Email:. Colleague's Email:. Separate multiple e-mails with a ;. Thought you might appreciate this item s I saw at Current Opinion in Neurology. Send a copy to your email. Some error has occurred while processing your request. Please try after some time. Article as PDF Back to Top Article Outline. Box 1. Idiopathic intracranial hypertension : consensus guidelines on management.

J Neurol Neurosurg Psychiatry ; — Cited Here Understanding idiopathic intracranial hypertension : mechanisms, management, and future directions. Lancet Neurol ; — PubMed CrossRef. The expanding burden of idiopathic intracranial hypertension. Eye Lond ; Meta-analysis and systematic review of population-based epidemiological studies in idiopathic intracranial hypertension.

Eur J Neurol ; — Raised intracranial pressure in those presenting with headache. BMJ ; k Headache in idiopathic intracranial hypertension : findings from the idiopathic intracranial hypertension treatment trial. Headache ; — Advances in the understanding of headache in idiopathic intracranial hypertension.

Curr Opin Neurol ; — The idiopathic intracranial hypertension treatment trial: clinical profile at baseline. Evolving evidence in adult idiopathic intracranial hypertension : pathophysiology and management. Idiopathic intracranial hypertension : clinical nosography and field-testing of the ICHD diagnostic criteria. A case-control study. Cephalalgia ; — Headache determines quality of life in idiopathic intracranial hypertension. J Headache Pain ; What are the research priorities for idiopathic intracranial hypertension?

A priority setting partnership between patients and healthcare professionals. BMJ Open ; in press. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology ; — Is cerebrospinal fluid shunting in idiopathic intracranial hypertension worthwhile? A year review. European Headache Federation guideline on idiopathic intracranial hypertension.

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Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a Clinical Staging Scale. Arch Ophthalmol Am Med Assoc ; — Invest Ophthalmol Vis Sci ; — Characterising the patient experience of diagnostic lumbar puncture in idiopathic intracranial hypertension : a cross-sectional online survey.

BMJ Open ; 8: e Overdiagnosis of idiopathic intracranial hypertension. Optical coherence tomography to differentiate papilledema from pseudopapilledema. Curr Neurol Neurosci Rep ; J Neuroophthalmol ; — Enhanced depth imaging optical coherence tomography of optic nerve head drusen a comparison of cases with and without visual field loss. Ophthalmology ; —8. J Neurol ; — Effects of lowering cerebrospinal fluid pressure on the shape of the peripapillary retina in intracranial hypertension. Peripapillary retinal pigment epithelium layer shape changes from acetazolamide treatment in the Idiopathic Intracranial Hypertension Treatment Trial.

Optical coherence tomography for the diagnosis and monitoring of idiopathic intracranial hypertension. Macular thickness measurements with frequency domain-OCT for quantification of axonal loss in chronic papilledema from pseudotumor cerebri syndrome. Eye Lond ; — An overview of the clinical applications of optical coherence tomography angiography. Eye ; — Optical coherence tomography angiography at the acute phase of optic disc edema. Eye Vis Lond ; The utility of fundus fluorescein angiography in neuroophthalmology. Neuroophthalmology ; in press.

In the network, the easier a node can be influenced by the seed set, the higher the score it will gain and vice versa. Therefore, genes with high scores and ranked above a defined threshold form a disease-affected sub-network that is vulnerable to diseases. Similar definition is used to establish a drug-affected sub-network. The extent of overlap between the two sub-networks is used to predict whether the drug can effectively exert its influence on the disease.

This overlap can be quantitatively measured by an inner product of x disease and x drug so as to evaluate the performance of the drug in the treatment of the disease The equation is. Signaling pathways are relatively independent biomolecule subsystems or interaction sub-networks that carry out important biological tasks and complex information processing between molecules. Scoring signaling pathways allows us to identify biological processes influenced by diseases or regulated by drugs.

As shown in Fig. The details are provided below. Mapping gene scores generated in step 1 to the corresponding genes in pathways. For genes on the pathways that are not included in the background network, their scores are assigned as zero Fig. To determine if the TCM formula exerts significant effect s on the network, we generate a wide spectrum of random seed sets e.

Each seed set is randomly generated, containing the same number of target proteins as that of the original seed set. For each random counterpart, we compute its effect scores on each gene of the background network by equation 1. Here Z-score is introduced to quantify the score difference existing between the original seed set and its counterparts. It is expressed as follows:. These are considered as pathways significantly influenced by the disease or regulated by the drug.

The common pathways influenced by the disease and drug are used to measure drug efficacy from the biological perspective. SBP samples were ground into fine powder. Detailed extraction method was described in the ref. From the pharmaceutical perspective, proteins encoded by disease genes may serve as potential drug targets for treatment. Earlier network analysis of the DrugBank database revealed that certain FDA approved drugs, including those that treat cardiovascular diseases, preferentially target disease genes Table 1 summarizes the 11 common genes and their functions.

All 11 genes are associated with the functions of heart or blood vessels that are important in the etiology of CVD. To quantitatively display the effect of SBP on CVD treatment from a network perspective, we applied RWR algorithm to measure the impact of seed nodes on other nodes in the background network. To determine whether the network effect scores of the drug to disease are significant, we compared their scores with the scores obtained from random seed sets.

Based on the targets of SBPac and targets of SBPpc, we generated random target gene sets from the background network, respectively. The scores from random seed sets could be obtained using equation 1 and 2. The average and standard deviation values of effect scores for the random counterparts of each group were calculated. As shown in Table 2 , the Z-score values are This is because a Z-score value greater than 3 often indicates a statistically significant deviation between the actual value and the random ones. For those genes on the pathways that cannot be mapped, their scores were assigned zero.

The average value of all genes on each pathway was obtained. Microarray-based studies were performed to verify the network analysis results. A total of genes with mean expression ratios of SBP group to control group greater than 4 or less than 0.

Personalized medicine—a modern approach for the diagnosis and management of hypertension

Among these genes, only 31 and 9 genes are target genes of SBPac and SBPpc, respectively, identified by the bioinformatics method. The significantly expressed genes were set as the seed nodes and the corresponding component of the gene in the initial vector as normalized differential expression ratio. Among them, pathways are affected by CVD, which is It was found that 80 of the SBPac affected pathways and 70 of the 97 SBPpc affected pathways also appeared in these pathways, corresponding to Figure 4 shows the number of genes in different intersection sets of the four gene sets, and the number of pathways affected by genes in these intersections.

AB denotes the intersection set between A and B, and so on. These results suggest that SBP regulates CVD associated network through multi-components and multi-targets to achieve its clinical efficacy. The high consistency between the pathways identified by the bioinformatics methods and the microarray confirmation studies exemplifies the reliability of our data mining and analytical methods. Table 3 lists some of these pathways that are associated with CVD. Moreover, their encoded proteins are readily available.

Specific proteins were detected by Western blot as described in the Material and Methods. Each blot is representative of three independent experiments. Both ICAM-1 and COX-2 are expressed in endothelial cells and play important roles in the initiation and progression of cardiovascular disease. ICAM-1 facilitates the transmigration of leukocytes across vascular wall during inflammatory response. COX-2 converts arachidonic acid to various metabolites, including prostacyclin PGI2 , a major COX-2 metabolite found in endothelial cells and an effective vasodilator.

Second, we mapped the scores of all genes in the background network obtained through RWR, to pathways and calculated the regulation scores of CVD, all compounds of SBP and plasma absorbed compounds of SBP to these pathways. Finally, we validated our bioinformatics results in microarray- and Western blot-based studies.

However, from the perspective of network regulation, the sub-network regulated by SBP and most signaling pathways significantly regulated by SBP are overlapped with those influenced by CVD disease genes, respectively. These results suggest that SBP achieves its efficacy on CVD treatment by regulating the disease network though interactions between genes, instead of directly acting on CVD disease genes.

Finally, two important CVD associated disease genes that are targeted by SBP were validated at the protein expression level by Western blot. It shed lights on the modern approaches to investigate TCM pharmacology and to promote the development of traditional medicine. How to cite this article : Fang, H. Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Wang, L. Evaluation on tolerability and safety of long-term administration with shexiang baoxin pill in patients with coronary heart disease of stable angina pectoris.

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