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1.
Cureus ; 14(7): e26558, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35936129

RESUMO

Hiatal hernia is a condition where components of the abdominal cavity, most often a part of the stomach, penetrate through the diaphragm and into the chest cavity. The symptoms of hiatal hernias may differ secondary to their type and severity. The two main types of hiatal hernias are sliding and paraesophageal. Sliding hernias, which are more common and less of a cause for concern, are when the upper portion of the stomach and junction between the stomach and esophagus slides up into the thoracic cavity through a weakened diaphragm. These hernias account for the majority of all hiatal hernias, and their symptoms mimic those of gastroesophageal reflux disorder (GERD) due to laxity in the lower esophageal sphincter. Paraesophageal hernias occur when parts of the stomach and other abdominal organs protrude through the hiatus adjacent to an intact and in-place esophagus and stomach. Obesity and old age are risk factors for hiatal hernias, but they can occur in patients of any age and gender. Although some hiatal hernias may be asymptomatic, patients with positive symptoms may complain of heartburn, regurgitation of liquids and food back into their mouths, dysphagia, or discomfort and pain in the stomach or esophagus. Hiatal hernias are preferentially diagnosed with proper imaging, mainly with an upper gastrointestinal barium study, or by upper gastrointestinal endoscopy. The treatment for hiatal hernias depends on their severity and surgical repairs, if needed, are mostly done laparoscopically. In this case of a patient with a 3 cm hiatal hernia diagnosed with the help of esophagogastroduodenoscopy (EGD), the treatment did not require surgery. Instead, osteopathic manipulative treatment (OMT) was used to restore the functionality of the gastrointestinal tract and the placement of the gastroesophageal junction. The patient's symptoms were found to have improved after the application of OMT alone, with no symptoms of hiatal hernia and resolution of her somatic dysfunctions. The results of this case study suggest that OMT can be effectively utilized to treat the symptoms of hiatal hernias and may also be effective as a curative method as well.

2.
Biochemistry ; 56(40): 5338-5346, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-28952715

RESUMO

Ionizable groups buried in the hydrophobic interior of proteins are essential for energy transduction. These groups can have highly anomalous pKa values that reflect the incompatibility between charges and dehydrated environments. A systematic study of pKa values of buried ionizable groups in staphylococcal nuclease (SNase) suggests that these pKa values are determined in part by conformational reorganization of the protein. Lys-66 is one of the most deeply buried residues in SNase. We show that its apparent pKa of 5.7 reflects the average of the pKa values of Lys-66 in different conformational states of the protein. In the fully folded state, Lys-66 is deeply buried in the hydrophobic core of SNase and must titrate with a pKa of ≪5.7. In other states, the side chain of Lys-66 is fully solvent-exposed and has a normal pKa of ≈10.4. We show that the pKa of Lys-66 can be shifted from 5.7 toward a more normal value of 7.1 via the insertion of flanking Gly residues at positions 64 and 67 to promote an "open" conformation of SNase. Crystal structures and nuclear magnetic resonance spectroscopy show that in these Gly-containing variants Lys-66 can access bulk water as a consequence of overwinding of the C-terminal end of helix 1. These data illustrate that the apparent pKa values of buried groups in proteins are governed in part by the difference in free energy between different conformational states of the protein and by differences in the pKa values of the buried groups in the different conformations.


Assuntos
Nuclease do Micrococo/química , Cristalografia por Raios X , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Nuclease do Micrococo/metabolismo , Modelos Moleculares , Conformação Proteica , Termodinâmica
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