Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital indifference to pain with anhydrosis (CIPA) is a well-defined entity among a group of sensory deficiency syndromes. Children with this genetic disease are insensitive to pain and temperature and do not sweat and suffer from psychomotor retardation. Self-inflicted trauma may be severe and lead to insoluble orthopedic problems. To date, 11 cases have been reported. We have reviewed the literature and are describing two girls with CIPA, born to consanguine Jewish parents of Moroccan origin. Immunoglobulin deficiency has been reported in CIPA but an immunologic investigation on one of our cases showed only an early and transient deficiency of IgA. The presence in the family of a brother with ataxia telangiectasia and complete absence of IgA would seem to be irrelevant and it seems probable that the parents are heterozygotic for two disparate autosomal recessive syndromes.
 ...
PMID:Congenital insensitivity to pain with anhydrosis. Report of a family and review of literature with reference to immune deficiency. 9 93

1. Selective antagonism of 5-HT4 receptors may provide therapeutic benefit in certain disorders of the myocardium, alimentary and lower urinary tract. We now report on RS 39604, a novel and selective 5-HT4 receptor antagonist and compare its pharmacological properties with those of SB 204070. 2. In guinea-pig striatal membranes, both RS 39604 and SB 204070 inhibited specific binding of [3H]-GR 113808 in a concentration-dependent manner yielding pKi estimates of 9.1 and 10.9, respectively. RS 39604 displayed a low affinity (pKi < 6.5) for 5-HT1A, 5-HT2C, 5-HT3, alpha 1c, D1, D2, M1, M2, AT1, B1 and opioid mu receptors and moderate affinity for sigma 1, (pKi = 6.8) and sigma 2 (pKi = 7.8) sites. 3. In the rat isolated oesophagus, precontracted with carbachol, RS 39604 (30-300 nM) behaved as a competitive antagonist towards 5-HT-induced relaxation (pA2 = 9.3; Schild slope = 1.0). We and others have shown previously that SB 204070 behaves as an unsurmountable antagonist in this preparation (pA2 approximately 10.5). In the guinea-pig isolated ileal mucosa, RS 39604 (30 nM) antagonized 5-MeOT-induced increase in short-circuit current (pA2 = 9.1). 4. In anaesthetized vagotomized micropigs, RS 39604, administered by the i.v. or intraduodenal (i.duod.) route, produced dose-dependent inhibition of 5-HT-induced tachycardia (ID50 = 4.7 micrograms kg-1, i.v. and 254.5 micrograms kg-1, i.duod). At maximal doses of 30 micrograms kg-1, i.v. and 6 mg kg-1, i.duod., the inhibitory effects of RS 39604 lasted for more than 6 h. In this preparation, SB 204070 was as potent as RS 39604by the i.v. route but was inactive by the intraduodenal route at doses up to 3 mg kg-1.5. In conscious mice, RS 39604, administered by the i.p. or p.o. route, produced dose-depend entinhibition of 5-hydroxytryptophan (5-HTP)-induced diarrhoea (ID50= 81.3 microg kg-1, i.p. and 1.1 mg kg-1,p.o.). In this assay, SB 204070 was inactive by the oral route at doses up to 30 mg kg-1.6. In anaesthetized guinea-pigs, RS 39604 antagonized the contractile effect of 5-HT in the proximal colon by producing parallel, dextral displacement of the dose-response curve to 5-HT. The mean dose ratios to 5-HT at 0.1 mg kg-1, i.v., 1 mg kg-1, i.v. and 10 mg kg-1, i.duod. were 4.6, 30.7 and 10.8,respectively. SB 204070 behaved as an unsurmountable antagonist in this assay.7. In a model of visceral pain in conscious rats, RS 39604 (0.01-1 mg kg-1, i.v.) did not affect colorectal distension-induced increases in arterial pressure whereas morphine (1 mg kg-1, i.v.) produced significant inhibition of the response, implying that 5-HT4 receptors are not involved in nociception in this model.8. The data suggest that RS 39604 is a high affinity and selective 5-HT4 receptor antagonist that is orally active and long-lasting in vivo. It is concluded that RS 39604 may be the preferable probe to use for investigating the physiological and pathophysiological role of 5-HT4 receptors in vivo.
 ...
PMID:RS 39604: a potent, selective and orally active 5-HT4 receptor antagonist. 758 7

With reference to cases of American dentists sued for "malpractice" during the 80s, the authors summarise the causes why, initially, the American lawyers found it difficult to plead on behalf of their clients. Therefore, the authors suggest a number of measures in order to reduce the probability of being sued by patients. In particular, they focus attention on:--the duty to treat patients, with reference to experimentation on humans within the context of scientific research and citing the Declaration of Helsinki;--informed consent, with particular emphasis on the need to inform the patient regarding all aspects of treatment, including any risks or presumed complications that might arise during and after treatment;--professional liability, drawing a distinction between moral responsibility (regulated by the Code of Professional Practice) and legal liability (involving the legal field). Lastly, the authors underline the need to perfect and increase the awareness of the "management" risk of a dental practice, drawing special attention to the need to keep precise records on patients receiving treatment: radiographical and photographical examination, remote and recent medical history, the current state of teeth and gums, the presence of clicks and/or crepitus on ATM, cephalea, spontaneous and/or provoked pain involving masticatory and cervical muscles, obtaining the informed consent of the patient.
 ...
PMID:[Legal medicine and dentistry]. 892 85

Arterial hypertension must also be consistently treated in patients with PAD. Current guidelines and recommendations have to be considered, although in some patients the walk performance may be affected temporary by blood pressure dropping. In PAD, ideal antihypertensives are ACE inhibitors, AT1 receptor antagonists, calcium channel blockers and also alpha receptor blockers in combination. Beta receptor blockers-indicated in coronary heart disease-do not influence pain-free walking distance (PFWD) in patients with PAD. Diuretics should only be given in low dosage and in combination with other antihypertensive drugs in order to avoid a decrease of blood flow ability with clinical events.
 ...
PMID:[Risk adapted therapy in vascular diseases: antihypertensive treatment in peripheral arterial disease]. 1641 58

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers antagonists (ARAs) are widely used compounds in various cardiovascular disorders. ACEIs, but not ARAs, inhibit the enzyme dipeptidyl carboxypeptidase which is involved in the conversion of angiotensin I to II and degradation of kinins like bradykinin and substance P. Bradykinin and substance P are potent mediators of inflammation and pain. Hence the study was undertaken to evaluate the effects of captopril (an ACEI) and losartan (an ARA-AT1 receptor antagonist) on thermal and chemical induced nocioception by employing hot plate and acetic acid induced writhing tests respectively in mice. Inbred albino mice weighing between 25-30 g were used and they were divided into two sets, each set containing 7 groups. Control groups received normal saline and the remaining six groups received three doses (0.5, 1 and 2 mg/kg) of captopril and three doses (0.5, 1 and 2 mg/kg) of losartan. Drugs were administered intraperitoneally fifteen minutes before placing the animal over the hot plate or 30 minutes before injecting 0.6% acetic acid. Both drugs dose dependently reduced the reaction time in hot plate method. In chemical induced writhing test, both the drugs reduced the latency of onset of writhing and in captopril pretreated groups, acetic acid induced sustained abdominal contraction without any intermittent relaxation. However, in losartan pretreated animals acetic acid just increased the number of writhings without sustained abdominal contraction. Thus, our study suggests that both drugs have hyperalgesic effects.
 ...
PMID:Effects of captopril and losartan on thermal and chemical induced pain in mice. 1705 37

Pathology of the temporomandibular joint (TMJ) affects an important part of the population, though it is not viewed as a public health problem. Between 3-7% of the population seeks treatment for pain and dysfunction of the ATM or related structures. The literature reports great variability in the prevalence of the clinical symptoms (6-93%) and signs (0-93%), probably as a result of the different clinical criteria used. In imaging studies it is common to observe alterations that have no clinical expression of any kind. Radiographic changes corresponding to osteoarthrosis are observed in 14-44% of the population. Age is a risk factor, though with some particularities. In elderly patients there is an increased prevalence of clinical and radiological signs, though also a lesser prevalence of symptoms and of treatment demands than in younger adults. Approximately 7% of the population between 12 and 18 years of age is diagnosed with mandibular pain-dysfunction. Temporomandibular dysfunction (TMD) is more frequent in females. No clear relationship has been established between occlusal alterations and TMJ disease. Only disharmony between centric relation and maximum intercuspidation, and unilateral crossbite, have demonstrated a certain TMJ disease-predictive potential. Both local and systemic hyperlaxity has been postulated as a possible cause of TMD. Parafunctional habits and bruxism are considered risk factors of TMD with odds ratios (ORs) of up to 4.8. Psychophysiological theory holds stress as a determinant factor in myofascial pain. Genetic factors and orthodontic treatment have not been shown to cause TMD.
 ...
PMID:Review of temporomandibular joint pathology. Part I: classification, epidemiology and risk factors. 1766 15

In this second article we describe the more interesting pharmacological interactions in dental practice based on the prescription of analgesic narcotics, paracetamol and non-selective non-steroid anti-inflammatory drugs (NSAI) (which inhibit cyclooxigenase 1 -COX 1- and cyclooxigenase 2 -COX 2-) and selective NSAIs (COX 2 inhibitors). The importance of preventing the appearance of these pharmacological interactions is because these are medicaments prescribed daily in odontology for moderate pain treatment and inflammation in the oral cavity. Paracetamol can interact with warfarin and therefore care should be taken with chronic alcoholic patients. All NSAIs reduce renal blood flow and consequently are capable of reducing the efficacy of medicaments used for treating arterial hypertension, which act via a renal mechanism. Especial attention should be taken considering the risk of interaction between the antagonists of AT1 receptors of angiostensin II (ARAII) and the NSAIs.
 ...
PMID:Pharmacological interactions of anti-inflammatory-analgesics in odontology. 1917 55

To clarify the role of angiotensin II (Ang II) in the regulation of sensory signaling, we studied the effect of subpressor dose (150 ng/kg/min) of Ang II on pain-related behavior in relation with neuronal injury and activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRGs) after chronic constriction injury (CCI). Systemic continuous delivery of Ang II induced the tactile, heat and cold hyperlagesia, when measured at 7 days ofpost-injury. Blockade of the AT1 receptor with losartan (2.5 mg/kg/day) prevented tactile hyperalgesia and attenuated cold hyperalgesia, but did not affect the response to noxious heat stimulus. A marked increase of large-sized injured primary afferent neurons, detected by ATF3 immunolabeling, was seen in lower lumbar DRGs on ipsilateral side after Ang II treatment. Subpressor dose of Ang II induced an increase of activated SGCs (detected by GFAP immunolabeling) enveloping large-diameter neurons. Our results suggested that Ang II through the AT1 receptor activation is an important regulatory factor in neuropathic pain perception and plays an important role in the injury of large-sized primary afferent neurons and activation of SGCs elicited by the CCI.
 ...
PMID:Effect of subpressor dose of angiotensin II on pain-related behavior in relation with neuronal injury and activation of satellite glial cells in the rat dorsal root ganglia. 2356 80

We investigated the mechanisms underlying the endogenous control of nociception at the peripheral level during inflammation. We hypothesized that angiotensin receptors could modulate pain at the peripheral level via endogenous processes because angiotensin receptors are present in peripheral nerve terminals. We evaluated the role of the angiotensin receptors system (RAS) in the modulation of inflammatory and neuropathic pain states. Mas receptor KO mice exhibited major inflammatory pain compared to wild-type mice. Similar results were observed when rats were injected with the Mas receptor antagonist A779 or the AT1 receptor antagonist, losartan after inflammatory stimulation by carrageenan. However, these antagonists were not effective in animals with neuropathic-induced pain (e.g., sciatic nerve constriction). Therefore, RAS seems to play an important role in inflammatory but not neuropathic pain.
...
PMID:Participation of AT1 and Mas receptors in the modulation of inflammatory pain. 2516 53

We have recently reported that an intrathecal (i.t.) administration of angiotensin II (Ang II) into mice induces a nociceptive behavior accompanied by the activation of p38 MAPK signaling via AT1 receptors (Nemoto et al., 2013, Mol. Pain 9, 38). These results suggested that Ang II participates in the facilitation of nociceptive transmission in the spinal cord. In the present study, we used formalin test to examine the effect of i.t.-administered losartan, an AT1 receptor antagonist, and determine whether Ang II acts as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information. When administered i.t. 5 min before the injection of a 2% formalin solution into the plantar surface of the hindpaw, losartan (30-100 nmol) produced a dose-dependent and significant antinociceptive effect during both the first and second phases of the test. In the superficial dorsal horn of the spinal cord (laminae I and II), the fluorescence intensities for Ang II and phospho-p38 MAPK were both significantly increased on the ipsilateral side 3 min after the injection of formalin compared to saline-treated controls. Moreover, the increase of phospho-p38 MAPK fluorescence intensity was significantly inhibited by the i.t. administration of losartan (54.8 nmol) 5 min prior to formalin. These results indicate that losartan produces an antinociceptive effect through the inhibition of p38 MAPK phosphorylation in the mouse formalin test and that Ang II may act as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information.
 ...
PMID:The intrathecal administration of losartan, an AT1 receptor antagonist, produces an antinociceptive effect through the inhibiton of p38 MAPK phosphorylation in the mouse formalin test. 2544 71


1 2 Next >>