Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the course of routine plasma drug level monitoring an unexpected loss of seizure control and reduction in plasma phenytoin levels was noticed in two patients who were also taking 'Shankhapushpi' (SRC), an Ayurvedic preparation. Therefore, the present study was undertaken in rats to investigate any SRC-phenytoin interaction from both pharmacokinetic (serum levels) and pharmacodynamic (electroshock seizure prevention) aspects. Single dose SRC and phenytoin (oral/i.p.) coadministration did not have any effect on plasma phenytoin levels but decreased the antiepileptic activity of phenytoin significantly. On multiple-dose coadministration, SRC reduced not only the antiepileptic activity of phenytoin but also lowered plasma phenytoin levels. SRC itself showed significant antiepileptic activity compared to placebo and is worth further investigation. However, the clinical combination of SRC with phenytoin is not advised.
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PMID:Analysis of a clinically important interaction between phenytoin and Shankhapushpi, an Ayurvedic preparation. 154 1

Pediatric prehospital care was reviewed over a one-year period to determine success rate, causes of unsuccessful attempts, and complications of performing endotracheal intubation. The Milwaukee County Emergency Medicine Technician-Paramedics (EMT-Ps) responded to 1467 pediatric (less than 19 years of age) patient calls. This accounted for 11% of the patients who received EMT-P care during the study period. Of the 63 patients requiring pediatric endotracheal intubation, 49 (78%) were successfully intubated. Of the 42 pulseless nonbreathing (PNB) patients, 39 (93%) were successfully Of the 21 patients judged to be in impending respiratory failure, 10 (48%) were successfully intubated. Common difficulties in intubating the PNB patient included inability to visualize the glottis and cords secondary to mucus and/or vomitus, use of inappropriately small endotracheal tubes, and accidental extubation during transport. Difficulties in intubating impending respiratory failure patients included patient resistance and seizure activity. We recommend that the EMT-P training curriculum include a review of these difficulties and that prehospital pediatric endotracheal intubation performance be monitored and reviewed with the EMT-Ps.
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PMID:Prehospital pediatric endotracheal intubation performance review. 271 Jun 61

Because the initiation of IV lines by emergency medical technicians-Intermediates (EMT-Is) appeared to delay the patient's transport to the hospital, we undertook a retrospective study of 370 patients to compare prehospital care rendered by EMTs (EMT-A equivalent) and EMT-Is in a rural setting. Our study was limited to acute medical conditions in which protocols called for IV lines (124 patients with chest pain, 122 with acute respiratory distress, 99 with seizures, and only 25 with cardiac arrest) (the cardiac arrest cases were too few for statistical significance). We found that the difference in scene times for EMTs and EMT-Is not attempting IV lines was 6.1 and 6.9 minutes, respectively. The average scene time of EMT-Is attempting an IV line was 19.6 minutes (P less than .001) compared with EMT times, or times for EMT-Is not attempting an IV line. One hundred twenty-eight of 370 patients received IV medication within ten minutes of arrival in the emergency department, and ten of these patients had their IV lines initiated successfully in the field. Thirty-nine percent of patients with ED IV lines received IV medication within ten minutes of arrival, while only 21% of patients with a field IV line received medication in this period (P less than .05). We conclude that initiating a field IV line in this specific patient population significantly increased scene time and did not improve the chances of these patients receiving IV medication within ten minutes of arrival in the emergency department.
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PMID:Prehospital care by EMTs and EMT-Is in a rural setting: prolongation of scene times by ALS procedures. 271 61

The relationship between the physical fitness level (maximal O2 consumption, VO2max) and thermoregulatory reactions was studied in 17 adult males submitted to an acute cold exposure. Standard cold tests were performed in nude subjects, lying for 2 h in a climatic chamber at three ambient air temperatures (10, 5, and 1 degrees C). The level of physical fitness conditioned the intensity of thermoregulatory reactions to cold. For all subjects, there was a direct relationship between physical fitness and 1) metabolic heat production, 2) level of mean skin temperature (Tsk), 3) level of skin conductance, and 4) level of Tsk at the onset of shivering. The predominance of thermogenic or insulative reactions depended on the intensity of the cold stress: insulative reactions were preferential at 10 degrees C, or even at 5 degrees C, whereas colder ambient temperature (1 degree C) triggered metabolic heat production abilities, which were closely related to the subject's physical fitness level. Fit subjects have more efficient thermoregulatory abilities against cold stress than unfit subjects, certainly because of an improved sensitivity of the thermoregulatory system.
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PMID:Physical fitness and thermoregulatory reactions in a cold environment in men. 320 45

The understanding of epilepsy has advanced substantially in the past decade, and new anticonvulsant drugs with novel mechanisms of action are continually being developed. Some of these newer (and older) medications have been discussed in this article. A wide variety of other drugs is occasionally used in the management of epilepsy. Although parenteral magnesium sulfate is used mainly for the prevention and control of seizures in severe preeclampsia or eclampsia, parenteral magnesium sulfate may also be useful in controlling epileptic seizures associated with low plasma magnesium concentrations. Although considered obsolete, bromides have been useful in the management of tonic-clonic or myoclonic seizures in some infants and preadolescent children when other drugs were unsuitable. Acetazolamide may be useful in the management of refractory partial, myoclonic, absence or primary generalized tonic-clonic seizures; however, tolerance develops to the effect of the drug. Corticotropin and corticosteroids are sometimes used in the management of myoclonic seizures in infants. Steroids may be used in seizures due to intracerebral malignancies and metastasis but are more effective in blunting the intracranial swelling associated with these diseases. Recognition of these new drugs may allow the paramedic or EMT to identify seizure patients in the field. Knowledge of the side effects of these medications may be used to guide patients into appropriate treatment pathways.
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PMID:Anticonvulsant medications. 1145 38

A 32-year-old HIV-infected woman developed fever and systemic illness of unknown origin after being placed on phenytoin for seizures. Her clinical syndrome, skin biopsy findings, and clinical response to steroids were consistent with phenytoin hypersensitivity syndrome.
Int J STD AIDS 2005 Feb
PMID:Phenytoin hypersensitivity syndrome masquerading as fever and systemic illness of unknown origin in an HIV-infected patient. 1580 50

A rare episode of early neurosyphilis occurred in a 34-year-old, otherwise healthy, woman. Based on an isolated positive Borrelia burgdorferi serology (later interpreted as a cross-reaction), early ceftriaxone was initiated, in the suspect of Lyme borreliosis. Even after the diagnosis was corrected into that of a neurosyphilis, ceftriaxone administration was continued, until it achieved complete clinical and microbiological success after 24 days of treatment in a day-hospital setting, and three-weekly penicillin administrations. When considering the differential diagnosis, a luetic aetiology should not be underestimated when facing young patients with signs-symptoms of a meningoencephalitis. Our case report was characterized by an extremely low patient's age, compared with the occurrence of tertiary neurosyphilis, more than three years after the last sexual contacts. The diagnosis was confirmed by highly positive treponemal and non-treponemal serum and cerebrospinal fluid serology, and several suggestive clinical manifestations: seizures, altered mentation, cognitive impairment, lip drop, and anisochoria. These concomitant findings, together with a neuroradiological report indicating a diffuse meningoencephalitis, allowed us to confirm the diagnosis of neurosyphilis, together with a demonstrated cross-reaction of B. burgdorferi serology. Although ceftriaxone benefits from its once-daily administration (and can be easily delivered on outpatient basis), it is not the firstline treatment of neurosyphilis. However, our experience demonstrated a favourable and rapid response to ceftriaxone, in the absence of toxicity and disease sequelae.
Int J STD AIDS 2005 Dec
PMID:Neurosyphilis in a young adult: very early tertiary syphilis? 1633 71

Leptin plays a pivotal role in the regulation of energy homeostasis and metabolism, primarily by acting on neurons in the hypothalamus that control food intake. However, leptin receptors are more widely expressed in the brain suggesting additional, as yet unknown, functions of leptin. Here we show that both embryonic and adult hippocampal neurons express leptin receptors coupled to activation of STAT3 and phosphatidylinositol 3-kinase-Akt signaling pathways. Leptin protects hippocampal neurons against cell death induced by neurotrophic factor withdrawal and excitotoxic and oxidative insults. The neuroprotective effect of leptin is antagonized by the JAK2-STAT3 inhibitor AG-490, STAT3 decoy DNA, and phosphatidylinositol 3-kinase/Akt inhibitors but not by an inhibitor of MAPK. Leptin induces the production of manganese superoxide dismutase and the anti-apoptotic protein Bcl-xL, and stabilizes mitochondrial membrane potential and lessens mitochondrial oxidative stress. Leptin receptor-deficient mice (db/db mice) are more vulnerable to seizure-induced hippocampal damage, and intraventricular administration of leptin protects neurons against seizures. By enhancing mitochondrial resistance to apoptosis and excitotoxicity, our findings suggest that leptin signaling serves a neurotrophic function in the developing and adult hippocampus.
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PMID:Leptin-mediated cell survival signaling in hippocampal neurons mediated by JAK STAT3 and mitochondrial stabilization. 1799 59

Leptin is a hormone that reduces excitability in some hypothalamic neurons via leptin receptor activation of the JAK2 and PI3K intracellular signaling pathways. We hypothesized that leptin receptor activation in other neuronal subtypes would have anticonvulsant activity and that intranasal leptin delivery would be an effective route of administration. We tested leptin's anticonvulsant action in 2 rodent seizure models by directly injecting it into the cortex or by administering it intranasally. Focal seizures in rats were induced by neocortical injections of 4-aminopyridine, an inhibitor of voltage-gated K+ channels. These seizures were briefer and less frequent upon coinjection of 4-aminopyridine and leptin. In mice, intranasal administration of leptin produced elevated brain and serum leptin levels and delayed the onset of chemical convulsant pentylenetetrazole-induced generalized convulsive seizures. Leptin also reduced neuronal spiking in an in vitro seizure model. Leptin inhibited alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor-mediated synaptic transmission in mouse hippocampal slices but failed to inhibit synaptic responses in slices from leptin receptor-deficient db/db mice. JAK2 and PI3K antagonists prevented leptin inhibition of AMPAergic synaptic transmission. We conclude that leptin receptor activation and JAK2/PI3K signaling may be novel targets for anticonvulsant treatments. Intranasal leptin administration may have potential as an acute abortive treatment for convulsive seizures in emergency situations.
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PMID:Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. 1809 79

Neuronal cell death caused by pathophysiological over-activation of glutamate receptors and the subsequent CaII overloading, has been implicated in neurodegeneration after stroke, cerebral trauma and epileptic seizures. Recent findings suggest that certain progesterone metabolites (neurosteroids) such as allopregnanolone and dehydroepiandrosterone can protect neuronal cells from such insults. In the present study, murine P19 cells were induced to differentiate into postmitotic neurons expressing specific neuronal markers, including GABA(A) and NMDA receptors. Activation of NMDA receptors in P19-N neurons resulted in excitotoxic cell death, which involved suppression of the phosphorylation of the survival kinase PKB/Akt. Allopregnanolone and DHEA induced a rapid and prolonged phosphorylation of the Akt kinase and they were able to reverse the NMDA-induced suppression of the PI3-K/Akt pathway. The specificity of the neuroprotective effects of these neurosteroids was confirmed by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin, as well as by the GABA(A) receptor antagonist, bicuculline. The neurotoxic effect of NMDA on P19-N neurons was directly correlated with increased CaII entry, since the addition of EGTA or BAPTA-AM, significantly suppressed the NMDA-induced decrease of phospho-Akt and subsequent neuronal death. These results suggest that neurosteroids are able to act as survival factors on P19-N neurons, promoting the activation of the PI3-K/Akt pathway through a calcium-entry dependent mechanism.
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PMID:Induction of Akt by endogenous neurosteroids and calcium sequestration in P19 derived neurons. 1852


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