RESUMEN
OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a chronic disease with numerous complications that increase mortality and reduce the quality of life (QoL). The current study compares QoL in T2DM patients treated with insulin to those treated with oral antihyperglycemics (OAHs), as well as the frequency and severity of depression in patients. SUBJECTS AND METHODS: This prospective cross-sectional study included 200 patients with insulin or OAHs. Triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol levels were measured. The Beck Depression Inventory and the SF-36 Quality of Life Questionnaire were used to assess depression symptoms and QoL in response to different treatment modalities. RESULTS: Insulin-treated patients have a longer duration of illness, higher preprandial glycemic levels, lower scores in three of four dimensions of the SF-36 physical component, and a lower score in the SF-36 psychological component's emotional role dimension. Patients on insulin have milder depression symptoms than those with OAHs. Depression symptoms, according to the findings, worsen QoL and glycemic control in insulin-treated patients. CONCLUSIONS: According to these findings, any treatment modality's success in T2DM patients primarily depends on psychological support and preventive measures that promote and maintain mental health.
Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Depresión/complicaciones , Calidad de Vida , Estudios Transversales , Estudios Prospectivos , Insulina/uso terapéutico , ColesterolRESUMEN
The responses of liver glucocorticoid receptor (GR) and genes coding for a glucocorticoid-inducible tyrosine aminotransferase (TAT) and two acute-phase proteins (APP) [alpha2-macroglobulin (alpha2-M) and gamma-fibrinogen (Fb)] to changes in glucocorticoid (GC) and proinflammatory (AP) cytokine contents have been examined in rats after single or combined treatments with turpentine oil, dexamethasone (Dex) and adrenalectomy. Activation of two APP genes in turpentine-induced inflammation was accompanied by an increase in the level of GR mRNA and a preferential translocation of GR-GC complexes to the nucleoplasm, while the expression of TAT remained unaltered. Dex alone caused a decrease in the levels of GR and Fb mRNAs, activation of TAT and alpha2-M genes, a decrease in the affinity of hormone binding sites and redistribution of translocated GR-Dex complexes within the nuclei. Inflammation potentiated the effect which Dex alone exerted on the GR content and the number of GR binding sites but counteracted its influence on the affinity of GR binding sites and nuclear distribution of GR-Dex complexes. Adrenalectomy promoted a fall in TAT mRNA, no changes in the GR and Fb mRNA, a decrease in the affinity of GR hormone binding sites and redistribution of GR-hormone complexes within the nuclei. The AP cytokines released in response to inflammation exerted a counteracting effect on the adrenalectomy-induced changes in the affinity of hormone binding sites and nuclear distribution of GR-hormone complexes. They potentiated a fall of TAT mRNA but promoted full expression of the Fb gene. These results argue strongly for the influence of AP cytokines on the functional state of the GR and GC signaling pathways.
Asunto(s)
Adrenalectomía , Citocinas/farmacología , Dexametasona/farmacología , Fibrinógeno/biosíntesis , Regulación de la Expresión Génica/efectos de los fármacos , Glucocorticoides/farmacología , Hígado/efectos de los fármacos , Receptores de Glucocorticoides/biosíntesis , Tirosina Transaminasa/biosíntesis , alfa-Macroglobulinas/biosíntesis , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Regulación hacia Abajo/efectos de los fármacos , Inducción Enzimática/efectos de los fármacos , Fibrinógeno/genética , Inflamación/inducido químicamente , Inflamación/metabolismo , Irritantes/toxicidad , Hígado/metabolismo , Masculino , ARN Mensajero/biosíntesis , Ratas , Ratas Wistar , Receptores de Glucocorticoides/genética , Trementina/toxicidad , Tirosina Transaminasa/genética , Regulación hacia Arriba/efectos de los fármacos , alfa-Macroglobulinas/genéticaRESUMEN
Reductions in growth rate caused by fusidic acid-resistant EF-G mutants in Salmonella typhimurium correlate strongly with increased mean cell size. This is unusual because growth rate and cell size normally correlate positively. The global transcription regulator molecule ppGpp has a role in co-ordinating growth rate and division, and its basal level normally correlates inversely with cell size at division. We show that fusidic acid-resistant EF-G mutants have perturbed ppGpp basal levels during steady-state growth and perturbed induced levels during starvation. One mutation, fusA1, associated with the slowest growth rate and largest cell size, causes a reduction in the basal level of ppGpp to one-third of that found in the wild-type strain. Other fusA mutants with intermediate or wild-type growth rates and cell sizes have either normal or increased basal levels of ppGpp. There is an inverse relationship between the basal level of ppGpp in vivo and the degree to which translation dependent on mutant EF-G is inhibited by ppGpp in vitro. This enhanced interaction between mutant EF-G and ppGpp correlates with an increased KM for GTP. Our results suggest that mutant EF-G modulates the production of ppGpp by the RelA (PSI) pathway. In conclusion, fusidic acid-resistant EF-G mutations alter the level of ppGpp and break the normal relationship between growth rate and cell size at division. It would not be surprising if other phenotypes associated with these mutants, such as loss of virulence, were also related to perturbations in ppGpp levels effected through altered transcription patterns.
Asunto(s)
Antibacterianos/farmacología , Ácido Fusídico/farmacología , Guanosina Tetrafosfato/metabolismo , Factor G de Elongación Peptídica/metabolismo , Salmonella typhimurium/efectos de los fármacos , Farmacorresistencia Microbiana , Mutación , Factor G de Elongación Peptídica/efectos de los fármacos , Factor G de Elongación Peptídica/genética , Biosíntesis de Proteínas , Salmonella typhimurium/genética , Salmonella typhimurium/crecimiento & desarrollo , Salmonella typhimurium/metabolismoRESUMEN
Hormonal requirements for full hepatic expression of alpha2-macroglobulin (alpha2M), alpha1-acid glycoprotein (AGP), haptoglobin (Hp) and gamma-fibrinogen (Fb) were assessed at the level of mRNA. Prior to exposure to turpentine-induced inflammation, rats were either depleted of glucocorticoids by adrenalectomy or supplemented with an excess of dexamethasone. Adrenalectomy alone did not affect the basal level of acute phase protein (APP) expression except for alpha2M mRNA, the level of which was enhanced. In contrast, dexamethasone treatment alone promoted full induction of alpha2M, significant, but not maximal increase of AGP and Hp mRNAs and suppression of Fb. In adrenalectomized rats, acute phase (AP)-cytokines, released in response to inflammation, promoted full expression of Fb and Hp and increased the level of AGP mRNA whereas alpha2M mRNA remained at the basal level. Inflammation in dexamethasone pretreated rats elicited changes which, in comparison to mRNA values for dexamethasone unpretreated inflamed rats, were seen as overexpression of alpha2M, full expression of AGP and incomplete expression of Hp, whereas Fb mRNA remained at the basal level. These data suggest that glucocorticoids are the principal inducers of alpha2M and AP-cytokines of Fb. For full induction of AGP, additive actions of glucocorticoids and AP-cytokines are required whereas expression of Hp is predominantly controlled by AP-cytokines.