Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous Ouabain (EO) and Adducin enhance the Na-K pump function and play an important role in sodium homeostasis and blood pressure (BP) regulation. In the general population, plasma EO modulates BP either by inhibiting the prohypertensive effect of an excessive salt intake or counteracting the depressor action of normal-moderate salt intake. Almost 50% of hypertensive patients have increased circulating plasma levels of EO. EO has been associated both to left ventricular dysfunction and hypertrophy. A new antihypertensive agent, PST2238, (17beta-(3-furyl)-5beta-androstan-3beta, 14beta, 17alpha-triol a digitoxigenin derivative) able to selectively antagonize both the EO and adducin prohypertensive and molecular effects, has been developed. In hypertensive rats (MHS strain) carrying both adducin mutations and increased plasma EO and in ouabain-infused rats (OS), PST2238 lowers BP by normalizing the renal Na-K pump function. In OS rats, PST antagonized the cardiac and renal pro-hypertrophic ouabain effect associated to the activation of the Src-EGFr-ERK(1/2) signaling cascade. Phase 1 clinical studies demonstrated a high tolerability of PST2238. In a preliminary phase 2 study on 42 mild never-treated hypertensive patients, PST2238 given for 3 months at 0.5 mg/day, significantly reduced BP in subjects with moderate salt intake, implying that it may be selectively effective in conditions where EO plays a prohypertensive role. In conclusion, PST2238, because of its peculiar action mechanism, represents a new tool to disentangle the complex relationship between salt intake, genetic control of renal sodium handling and EO effect.
 ...
PMID:A new antihypertensive agent that antagonizes the prohypertensive effect of endogenous ouabain and adducin. 1652 50

Previous studies have shown that there are profuse lymphatic tissues under the intestinal mucous membrane. Moreover, vaccine administered orally can elicit both mucous membrane and system immune response simultaneously, accordingly induce tumor-specific cytotoxic T lymphocyte. As a result, the oral route is constituted the preferred immune route for vaccine delivery theoretically. However, numerous vaccines especially protein/peptide vaccines remain poorly available when administered by this route. Nanoemulsion has been shown as a useful vehicle can be developed to enhance the antitumor immune response against antigens encapsulated in it and it is good for the different administration routes. Of particular interest is whether the protein vaccine following peroral route using nanoemulsion as delivery carrier can induce the same, so much as stronger antitumor immune response to following conventional ways such as subcutaneous (sc.) or not. Hence, in the present study, we encapsulated the MAGE1-HSP70 and SEA complex protein in nanoemulsion as nanovaccine NE (MHS) using magnetic ultrasound method. We then immuned C57BL/6 mice with NE (MHS), MHS alone or NE (-) via po. or sc. route and detected the cellular immunocompetence by using ELISpot assay and LDH release assay. The therapeutic and tumor challenge assay were examined then. The results showed that compared with vaccination with MHS or NE (-), the cellular immune responses against MAGE-1 could be elicited fiercely by vaccination with NE (MHS) nanoemulsion. Furthermore, encapsulating MHS in nanoemulsion could delay tumor growth and defer tumor occurrence of mice challenged with B16-MAGE-1 tumor cells. Especially, the peroral administration of NE (MHS) could induce approximately similar antitumor immune responses to the sc. administration, but the MHS unencapsulated with nanoemulsion via po. could induce significantly weaker antitumor immune responses than that via sc., suggesting nanoemulsion as a promising carrier can exert potent antitumor immunity against antigen encapsulated in it and make the tumor protein vaccine immunizing via po. route feasible and effective. It may have a broad application in tumor protein vaccine.
 ...
PMID:The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following peroral administration route. 1852 70

Hereditary sensory and autonomic neuropathy type IV (HSAN IV) is a very rare autosomal recessive disorder characterized by recurrent episodes of unexplained fever, extensive anhidrosis, total insensitivity to pain, hypotonia, and mental retardation. The absence of urticarial reaction to intradermal injection of histamine is a sign of great diagnostic value, but this is common to all types of HSAN. The most frequent complications of this disease are corneal scarring, multiple fractures, joint deformities, osteomyelitis, and disabling self-mutilations. Malignant hyperthermia and sepsis are major causes of mortality. We relate the first observations of two Tunisian children with genetically confirmed HSAN IV. Our goal is to review the clinical aspects of this mysterious neuropathy and to emphasize the peculiarities of its management. These two patients are brothers from 1st-degree consanguineous parents (cousins) with no particular medical history. The 1st patient, the family's 1st child, presented in the 1st h of life with hypotonia and persistent fever, which was refractory to antipyretics. At the age of 8 months, the patient presented recurrent febrile seizures and developed significant self-mutilations of the fingers and tongue. He died 3 months later in a context of multivisceral failure from sepsis and malignant hyperthermia. The 2nd patient, currently aged 4 years, was born after a normal sister. He consulted in the neonatal period for a high fever. The diagnosis of HSAN IV was rapidly suspected and genetically confirmed. In fact, this patient is homozygous for the NTRK1 gene, whereas his sister and both parents are heterozygous. Special predispositions have been taken to improve the course of the disease such as air conditioning to control hyperthermia, a dental tray to reduce the injuries resulting from self-mutilation, regular moistening of the eyes to avoid corneal drying, and chlorpromazine to control hyperactivity and reduce injuries. The good progression with all these predispositions and others underlines the importance of appropriate multidisciplinary management and close monitoring of patients suffering from HSAN IV, especially during the first 3 years of life. Indeed, mortality, behavioral disorders, and mental retardation significantly decrease after this age. New curative treatments are expected in the next decade.
 ...
PMID:[Hereditary sensory and autonomic neuropathy type IV: a report on two cases]. 2139 70