RESUMO
BACKGROUND: Long-term visit-to-visit glycemic variability is an additional measure of glycemic control. We aimed to evaluate the prognostic value of several measures of glycemic variability for the occurrence of micro- and macrovascular complications, and all-cause mortality in patients with type 2 diabetes. METHODS: 654 individuals were followed-up over a median of 9.3 years. Glycemic variability (SDs and coefficients of variation of HbA1c and fasting glycaemia) was measured during the first 12- and 24-months. Multivariate Cox analysis, adjusted for risk factors and mean HbA1c and fasting glycaemia levels, examined the associations between glycemic variability and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications [total cardiovascular events (CVE), major adverse CVEs (MACE) and cardiovascular mortality], and of all-cause mortality. RESULTS: During follow-up, 128 patients had a CVE (96 MACE), and 158 patients died (67 from cardiovascular diseases); 152 newly-developed or worsened diabetic retinopathy, 183 achieved the renal composite outcome (89 newly developed microalbuminuria and 91 deteriorated renal function), and 96 newly-developed or worsened peripheral neuropathy. Glycemic variability, particularly the 24-month parameters either estimated by HbA1c or by fasting glycemia, predicted all endpoints, except for retinopathy and peripheral neuropathy development/progression, and was a better predictor than mean HbA1c. Glycemic variability predicted retinopathy development/progression in patients with good glycemic control (HbA1c ≤ 7.5%, 58 mmol/mol) and predicted new-incident peripheral neuropathy. CONCLUSIONS: Long-term visit-to-visit glycemic variability is an additional and frequently a better glycemic parameter than mean HbA1c levels for assessing the risk of future development of micro- and macrovascular complications in patients with type 2 diabetes.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/epidemiologia , Hemoglobinas Glicadas/metabolismo , Idoso , Albuminúria/sangue , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Biomarcadores/sangue , Brasil/epidemiologia , Causas de Morte , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/mortalidade , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Retinopatia Diabética/sangue , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
Crohn's disease (CD) and ulcerative colitis (UC) are intestinal disorders that comprise the inflammatory bowel diseases (IBD). These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF) biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Escalas de Graduação Psiquiátrica , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Comparação Transcultural , Análise Fatorial , Hipercinese/psicologia , Comportamento Impulsivo/fisiologia , Psicometria , Reprodutibilidade dos Testes , Autorrelato , EspanhaRESUMO
Crohn's disease (CD) and ulcerative colitis (UC) are intestinal disorders that comprise the inflammatory bowel diseases (IBD). These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF) biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.
Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/terapia , Doença de Crohn/terapia , Imunossupressores/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos/métodos , Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Humanos , Doenças Inflamatórias Intestinais/terapia , Metotrexato/uso terapêutico , Microbiota/efeitos dos fármacos , Probióticos/uso terapêutico , Purinas/uso terapêutico , Qualidade de Vida , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.
Assuntos
Animais , Humanos , Trato Gastrointestinal/microbiologia , Predisposição Genética para Doença/etiologia , Interações Hospedeiro-Patógeno/imunologia , Doenças Inflamatórias Intestinais/etiologia , Microbiota/imunologia , Interação Gene-Ambiente , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Microbiota/genética , Polimorfismo GenéticoRESUMO
Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.
Assuntos
Trato Gastrointestinal/microbiologia , Predisposição Genética para Doença/etiologia , Interações Hospedeiro-Patógeno/imunologia , Doenças Inflamatórias Intestinais/etiologia , Microbiota/imunologia , Animais , Interação Gene-Ambiente , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Microbiota/genética , Polimorfismo GenéticoRESUMO
Injury triggers inflammatory responses and tissue repair. Several treatments are currently in use to accelerate healing; however, more efficient formulations are still needed for specific injuries. Since unsaturated fatty acids modulate immune responses, we aimed to evaluate their therapeutic effects on wound healing. Skin wounds were induced in BALB/c mice and treated for 5 days with n-3, n-9 fatty acids or vehicle (control). n-9 treated mice presented smaller wounds than control and n-3 at 120 h post-surgery (p.s.). Collagen III mRNA, TIMP1 and MMP9 were significantly elevated in n-9 group compared to n-3 or vehicle at 120 h p.s. Among the inflammatory mediators studied we found that IL-10, TNF-α and IL-17 were also higher in n-9 treated group compared to n-3 or vehicle at 120 h p.s. Interestingly, COX2 had decreased expression on wound tissue treated with n-9. Inflammatory infiltrate analysis revealed diminished frequency of CD4(+), CD8(+) and CD11b(+) cells in n-9 wounds at 24 and 120 h p.s., which was not related to cell death, since in vitro apoptosis experiments did not show any cell damage after fatty acids administration. These results suggested that unsaturated fatty acids, specifically n-9, modulate the inflammation in the wound and enhance reparative response in vivo. n-9 may be a useful tool in the treatment of cutaneous wounds.
Assuntos
Ácidos Linolênicos/farmacologia , Ácido Oleico/farmacologia , Pele/imunologia , Pele/lesões , Cicatrização/efeitos dos fármacos , Cicatrização/imunologia , Animais , Apoptose , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Colágeno/genética , Ciclo-Oxigenase 2/genética , Citometria de Fluxo , Expressão Gênica , Inflamação , Interleucina-10/sangue , Interleucina-17/sangue , Ácidos Linolênicos/uso terapêutico , Macrófagos/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ácido Oleico/uso terapêutico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/efeitos dos fármacos , Pele/crescimento & desenvolvimento , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
Plathymenia reticulata Benth has an anti-inflammatory effect and is capable of neutralizing the neuromuscular blockade induced by Bothrops jararacussu or Crotalus durissus terrificus venoms, probably by precipitating venom proteins (an effect caused by plant tannins). The present study aimed to evaluate the mutagenic activity of P. reticulata by using the Salmonella mutagenicity assay (Ames test) and the micronucleus test in CHO-K1 cells. P. reticulata extract concentrations of 2.84, 5.68, 11.37, and 19.90 mg/plate were assayed by the Ames test using TA97a, TA98, TA100 and TA102 bacterial strains, with (+S9) and without (-S9) metabolic activation. Concentrations of 5, 1.6 and 0.5 μg/mL of P. reticulata extract were used for the micronucleus test. P. reticulata extract was mutagenic to TA98 (-S9) and showed signs of mutagenic activity in TA97a and TA102 (both -S9) strains. Micronucleus test CBPI values showed that the endogenous metabolic system increased the number of viable cells when compared to the non-activated samples and the micronucleus frequency increased when the cells were treated in the absence of S9. We concluded that P. reticulata extract may present direct mutagenic properties.(AU)
Assuntos
Humanos , Testes de Mutagenicidade/métodos , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/farmacologiaRESUMO
Plathymenia reticulata Benth has an anti-inflammatory effect and is capable of neutralizing the neuromuscular blockade induced by Bothrops jararacussu or Crotalus durissus terrificus venoms, probably by precipitating venom proteins (an effect caused by plant tannins). The present study aimed to evaluate the mutagenic activity of P. reticulata by using the Salmonella mutagenicity assay (Ames test) and the micronucleus test in CHO-K1 cells. P. reticulata extract concentrations of 2.84, 5.68, 11.37, and 19.90 mg/plate were assayed by the Ames test using TA97a, TA98, TA100 and TA102 bacterial strains, with (+S9) and without (-S9) metabolic activation. Concentrations of 5, 1.6 and 0.5 ìg/mL of P. reticulata extract were used for the micronucleus test. P. reticulata extract was mutagenic to TA98 (-S9) and showed signs of mutagenic activity in TA97a and TA102 (both -S9) strains. Micronucleus test CBPI values showed that the endogenous metabolic system increased the number of viable cells when compared to the non-activated samples and the micronucleus frequency increased when the cells were treated in the absence of S9. We concluded that P. reticulata extract may present direct mutagenic properties.
Assuntos
Anti-Inflamatórios , Bothrops , Venenos de Crotalídeos , Crotalus cascavella , Solução Hidroalcoólica , Bloqueadores Neuromusculares , Plantas Medicinais , Testes de Mutagenicidade/métodosRESUMO
OBJECTIVE: To determine whether camel's milk can be consumed by patients intolerant to lactose without undesirable reactions. PATIENTS AND METHOD: Twenty-five patients with clinical and laboratorial diagnosis of lactose intolerance underwent provocation tests with growing amounts of cow's milk and subsequently with camel's milk. RESULTS: Except for two patients, who had mild reactions to the maximum dosage of camel's milk (250 mL), the acceptance was excellent. Pasteurization of camel's milk did not affect tolerance. Also, most of the patients showed significant clinical reactions when drinking very low amounts of cow's milk. CONCLUSION: Camel's milk can be considered an option for the individuals intolerant to lactose who present symptoms when ingesting cow's milk.
Assuntos
Intolerância à Lactose , Leite , Adolescente , Adulto , Idoso , Animais , Camelus , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4(+) leukocytes in the inflammatory infiltrate on days +7 and +14 and of CD8(+) cells on day +7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that high-dose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.