Quaternary Ammonium Compounds
Amino Acid Sequence
Dose-Response Relationship, Drug
Molecular Sequence Data
Lung Diseases, Obstructive
Chromatography, High Pressure Liquid
Electrophoresis, Polyacrylamide Gel
Forced Expiratory Volume
Nebulizers and Vaporizers
Indicators and Reagents
Trimethyl Ammonium Compounds
Electrophoresis, Agar Gel
Chromatography, Ion Exchange
Phospholipase C delta
Neuromuscular Blocking Agents
Nucleic Acid Conformation
Pulmonary Disease, Chronic Obstructive
Neuromuscular Nondepolarizing Agents
Dissent and Disputes
Thermodynamic analysis of halide binding to haloalkane dehalogenase suggests the occurrence of large conformational changes. (1/418)Haloalkane dehalogenase (DhlA) hydrolyzes short-chain haloalkanes to produce the corresponding alcohols and halide ions. Release of the halide ion from the active-site cavity can proceed via a two-step and a three-step route, which both contain slow enzyme isomerization steps. Thermodynamic analysis of bromide binding and release showed that the slow unimolecular isomerization steps in the three-step bromide export route have considerably larger transition state enthalpies and entropies than those in the other route. This suggests that the three-step route involves different and perhaps larger conformational changes than the two-step export route. We propose that the three-step halide export route starts with conformational changes that result in a more open configuration of the active site from which the halide ion can readily escape. In addition, we suggest that the two-step route for halide release involves the transfer of the halide ion from the halide-binding site in the cavity to a binding site somewhere at the protein surface, where a so-called collision complex is formed in which the halide ion is only weakly bound. No large structural rearrangements are necessary for this latter process. (+info)
Chloride dependence of hyperpolarization-activated chloride channel gates. (2/418)1. ClC proteins are a class of voltage-dependent Cl- channels with several members mutated in human diseases. The prototype ClC-0 Torpedo channel is a dimeric protein; each subunit forms a pore that can gate independently from the other one. A common slower gating mechanism acts on both pores simultaneously; slow gating activates ClC-0 at hyperpolarized voltages. The ClC-2 Cl- channel is also activated by hyperpolarization, as are some ClC-1 mutants (e.g. D136G) and wild-type (WT) ClC-1 at certain pH values. 2. We studied the dependence on internal Cl- ([Cl-]i) of the hyperpolarization-activated gates of several ClC channels (WT ClC-0, ClC-0 mutant P522G, ClC-1 mutant D136G and an N-terminal deletion mutant of ClC-2), by patch clamping channels expressed in Xenopus oocytes. 3. With all these channels, reducing [Cl-]i shifted activation to more negative voltages and reduced the maximal activation at most negative voltages. 4. We also investigated the external halide dependence of WT ClC-2 using two-electrode voltage-clamp recording. Reducing external Cl- ([Cl-]o) activated ClC-2 currents. Replacing [Cl-]o by the less permeant Br- reduced channel activity and accelerated deactivation. 5. Gating of the ClC-2 mutant K566Q in normal [Cl-]o resembled that of WT ClC-2 in low [Cl-]o, i.e. channels had a considerable open probability (Po) at resting membrane potential. Substituting external Cl- by Br- or I- led to a decrease in Po. 6. The [Cl-]i dependence of the hyperpolarization-activated gates of various ClC channels suggests a similar gating mechanism, and raises the possibility that the gating charge for the hyperpolarization-activated gate is provided by Cl-. 7. The external halide dependence of hyperpolarization-activated gating of ClC-2 suggests that it is mediated or modulated by anions as in other ClC channels. In contrast to the depolarization-activated fast gates of ClC-0 and ClC-1, the absence of Cl- favours channel opening. Lysine 556 may be important for the relevant binding site. (+info)
Human extracellular water volume can be measured using the stable isotope Na234SO4. (3/418)The volume of human extracellular water (ECW) may be estimated from the sulfate space (SS). Although it may better approximate ECW volume than the bromide space, a common alternative, SS measurement is limited by the need to administer a radioactive substance, sodium [35S]sulfate. In this paper, we demonstrate the measurement of the SS using the stable isotope, sodium [34S]sulfate. Eight healthy nonobese men ingested 0.50-0.78 mg (3.47-5.42 micromol) Na234SO4/kg body weight and 30 mg NaBr/kg body weight. Sulfate concentrations and 34SO4 enrichments were measured by electrospray tandem mass spectrometry before and during the 5 h after tracer administration. SS was calculated by linear extrapolation of the natural logarithm of serum 34SO4 concentrations obtained at h 2, 3 and 4 compared with h 3, 4 and 5. The SS obtained using values between h 3 and 5 (187 +/- 17 mL/kg) was similar to published determinations using intravenous or oral radiosulfate, and was 80% of the simultaneously measured corrected bromide space (234 +/- 10 mL/kg, P = 0.01). Oral sodium [34S]sulfate administration is a suitable technique for measuring ECW and avoids radiation exposure. (+info)
Bromine K-edge EXAFS studies of bromide binding to bromoperoxidase from Ascophyllum nodosum. (4/418)Bromine K-edge EXAFS studies have been carried out for bromide/peroxidase samples in Tris buffer at pH 8. The results are compared with those of aqueous (Tris-buffered) bromide and vanadium model compounds containing Br-V, Br-C(aliphatic) and Br-C(aromatic) bonds. It is found that bromide does not coordinate to the vanadium centre. Rather, bromine binds covalently to carbon. A possible candidate is active site serine. (+info)
Agonist-induced sensitization of beta-adrenoceptor signaling in neonatal rat heart: expression and catalytic activity of adenylyl cyclase. (5/418)Agonist stimulation of neonatal cardiac beta-adrenoceptors produces heterologous sensitization of adenylyl cyclase (AC) signaling, rather than desensitization, as seen in adults. We examined the ontogenetic patterns of AC expression and activity, and evaluated isoproterenol effects on this pattern. [(3)H]Forskolin binding showed an increase in AC concentration across the period (birth to 25 days of age) in which agonist-induced sensitization is replaced by desensitization; binding affinity also increased, suggesting a shift in conformation and/or isoform. Indeed, catalytic properties of AC changed substantially with development, as evaluated by AC responses to forskolin versus Mn(2+). In contrast, there were only minor changes in the levels of mRNAs encoding the two major isoforms. Neonates given repeated isoproterenol treatment showed an enhancement of [(3)H]forskolin binding B(max) and a precocious shift to the mature affinity state and corresponding catalytic properties. Although isoproterenol caused significant increases in AC mRNAs, the effects were small and showed no isoform preference. Thus, a primary mode for ontogenetic increases in cardiac cellular responsiveness to adrenergic stimulation is the increase in AC activity attendant upon an absolute increase in the membrane concentration of AC molecules, along with changes in the catalytic properties of AC. The lack of correlation between mRNA and AC protein suggests that the primary regulatory events are post-transcriptional. The induction of AC by beta-adrenoceptor stimulation in the fetus and neonate accounts for heterologous, agonist-induced sensitization, a phenomenon that preserves cellular responses during the period of the perinatal transition. (+info)
Evidence for de novo production of self-replicating and environmentally adapted RNA structures by bacteriophage Qbeta replicase. (6/418)Highly purified coliphage Qbeta replicase when incubated without added template synthesizes self-replicating RNA species in an autocatalytic reaction. In this paper we offer strong evidence that this RNA production is directed by templates generated de novo during the lag phase. Contamination of the enzyme by traces of RNA templates was ruled out by the following experimental results: (1) Additional purification steps do not eliminate this RNA production. (2) The lag phase is lengthened to several hours by lowering substrate or enzyme concentration. At a nucleoside triphosphate concentration of 0.15 mM no RNA is produced although the template-directed RNA synthesis works normally. (3) Different enzyme concentrations lead to RNA species of completely different primary structure. (4) Addition of oligonucleotides or preincubation with only three nucleoside triphosphates affects the final RNA sequence. (5) Manipulation of conditions during the lag phase results in the production of RNA structures that are adapted to the particular incubation conditions applied (e.g., RNA resistant to nuclease attack or resistant to inhibitors or even RNAs "addicted to the drug," in the sense that they only replicate in the presence of a drug like acridine orange). RNA species obtained in different experiments under optimal incubation conditions show very similar fingerprint patterns, suggesting the operation of an instruction mechanism. A possible mechanism is discussed. (+info)
Resonance raman spectra of manganese (III) tetraphenylporphin halides. (7/418)Unique resonance Raman spectra were obtained when manganese(III) tetraphenylporphin halides in noncoordinating solvents were illuminated by laser frequencies around 500 nm. Of particular interest is the observation of a feature that is sensitive to the nature of the axial ligand. This feature disappears when the coordinating solvent pyridine is employed, and it, therefore, appears to be diagnostic of the manganese coordination number. (+info)
Randomised controlled trial of postnatal sodium supplementation on body composition in 25 to 30 week gestational age infants. (8/418)AIMS: To compare the effects of early and delayed sodium supplementation on body composition and body water compartments during the first two weeks of postnatal life. METHODS: Preterm infants of 25-30 weeks' gestation were stratified and randomly assigned according to gender and gestational age, to receive a sodium intake of 4 mmol/kg/day beginning either on the second day after birth or when weight loss of 6% of birthweight had been achieved. Daily sodium intake, total fluid intake, energy intake, urine volume, and urinary sodium excretion were recorded. Total body water was measured by H(2)(18)O dilution on days 1, 7, and 14, and extracellular fluid volume by sodium bromide dilution on days 1 and 14. RESULTS: Twenty four infants received early, and 22 delayed, sodium supplementation. There were no significant differences between the groups in body water compartments on day 1. In the delayed group, but not the early group, there was a significant loss of total body water during the first week (delayed -44 ml/kg, p=0. 048; early 6 ml/kg, p=0.970). By day 14 the delayed, but not the early group, also had a significant reduction in extracellular fluid volume (delayed -53 ml/kg, p=0.01; early -37 ml/kg, p=0.2). These changes resulted in a significant alteration in body composition at the end of the first week (total body weight: delayed 791 ml/kg; early 849 ml/kg, p=0.013). By day 14 there were once again no significant differences in body composition between the two groups. CONCLUSIONS: Body composition after preterm birth is influenced by the timing of introduction of routine sodium supplements. Early sodium supplementation can delay the physiological loss of body water that is part of normal postnatal adaptation. This is likely to be of particular relevance to babies with respiratory distress syndrome. A tailored approach to clinical management, delaying the introduction of routine sodium supplements until there has been postnatal loss of body water, is recommended. (+info)
There are several types of lung diseases that are classified as obstructive, including:
1. Chronic obstructive pulmonary disease (COPD): This is a progressive condition that makes it hard to breathe and can cause long-term disability and even death. COPD is caused by damage to the lungs, usually from smoking or exposure to other forms of pollution.
2. Emphysema: This is a condition where the air sacs in the lungs are damaged and cannot properly expand and contract. This can cause shortness of breath and can lead to respiratory failure.
3. Chronic bronchitis: This is a condition where the airways in the lungs become inflamed and narrowed, making it harder to breathe.
4. Asthma: This is a condition where the airways in the lungs become inflamed and narrowed, causing wheezing, coughing, and shortness of breath.
5. Bronchiectasis: This is a condition where the airways in the lungs become damaged and widened, leading to thickening of the walls of the airways and chronic infection.
6. Pulmonary fibrosis: This is a condition where the lung tissue becomes scarred and stiff, making it harder to breathe.
7. Lung cancer: This is a malignant tumor that can occur in the lungs and can cause breathing difficulties and other symptoms.
These diseases can be caused by a variety of factors, including smoking, exposure to air pollution, genetics, and certain occupations or environments. Treatment for obstructive lung diseases may include medications, such as bronchodilators and corticosteroids, and lifestyle changes, such as quitting smoking and avoiding exposure to pollutants. In severe cases, surgery or lung transplantation may be necessary.
It's important to note that these diseases can have similar symptoms, so it's important to see a doctor if you experience any persistent breathing difficulties or other symptoms. A proper diagnosis and treatment plan can help manage the condition and improve quality of life.
* Cerebral encephalocele: when the brain tissue protrudes through the skull.
* Meningoencephalocele: when the meninges (the protective covering of the brain and spinal cord) protrude through the skull along with the brain tissue.
* Mesenchymal encephalocele: when other tissues such as skin, muscle or bone protrude through the skull along with the brain tissue.
Symptoms of encephalocele can vary depending on the severity of the defect and can include:
* Protrusion of the brain or meninges through a opening in the skull
* Abnormal appearance of the head or face
* Delayed developmental milestones such as sitting, standing or walking
* Poor muscle tone
* Vision and hearing problems
Diagnosis of encephalocele is typically made through a combination of physical examination, imaging studies such as CT or MRI scans, and genetic testing. Treatment for encephalocele usually involves surgery to repair the opening in the skull and relieve any pressure on the brain. In some cases, additional surgeries may be necessary to correct other defects such as hydrocephalus (fluid accumulation in the brain).
Encephalocele is a rare condition, but it can have serious consequences if left untreated. Early detection and intervention are important for improving outcomes and reducing the risk of complications.
1. Chronic bronchitis: This condition causes inflammation of the bronchial tubes (the airways that lead to the lungs), which can cause coughing and excessive mucus production.
2. Emphysema: This condition damages the air sacs in the lungs, making it difficult for the body to take in oxygen and release carbon dioxide.
The main causes of COPD are smoking and long-term exposure to air pollution, although genetics can also play a role. Symptoms of COPD can include shortness of breath, wheezing, and coughing, particularly during exercise or exertion. The disease can be diagnosed through pulmonary function tests, chest X-rays, and blood tests.
There is no cure for COPD, but there are several treatment options available to manage the symptoms and slow the progression of the disease. These include medications such as bronchodilators and corticosteroids, pulmonary rehabilitation programs, and lifestyle changes such as quitting smoking and increasing physical activity. In severe cases, oxygen therapy may be necessary to help the patient breathe.
Prevention is key in avoiding the development of COPD, and this includes not smoking and avoiding exposure to air pollution. Early detection and treatment can also help manage the symptoms and slow the progression of the disease. With proper management, many people with COPD are able to lead active and productive lives.