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Tuberculosis remains a serious threat to human health as an infectious disease in Mexico. Data about the genotypes of circulating Mycobacterium tuberculosis isolates (MTB) in the State of Nuevo Leon, Mexico are scarce. We aimed to determine the genotypes of circulating MTB belonging to the Beijing lineage recovered from patients in the State of Nuevo Leon, Mexico. A total of 406 MTB isolates from this state were genotyped using the spoligotyping method and 18-locus MIRU-VNTR. Lineage classification and MTB transmission analysis were performed. Based on the spoligotyping analysis, we found 24 strains belonging to the Beijing genotype that were characterized phylogenetically. The MIRUs showed greater discriminatory power than the standard RFLP-IS6110 method; therefore, the greatest allelic diversity among the Beijing strains was observed with MIRU10, MIRU31, MIRU39, MRU40, and MIRU 26. MVLA analysis showed a profile variation between Beijing and non-Beijing strains. The minimum spanning tree (MST) showed that 79% (19) of the strains are related. All Beijing strains exhibited the deletion of region TbD1, which is a characteristic of modern strains. The application of spoligotyping and MIRU-VNTR-18 methods together proved to be more sensitive, discriminatory, and rapid than the standard method for the epidemiological analysis of Mycobacterium Beijing isolates. This study is one of the first to describe the genomic diversity of M. Beijing in the State of Nuevo Leon, Mexico.
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The objective of this work was to identify genetic variants in Mexican patients diagnosed with hypertrophic cardiomyopathy (HCM). According to world literature, the genes mainly involved are MHY7 and MYBPC3, although variants have been found in more than 50 genes related to heart disease and sudden death, and to our knowledge there are no studies in the Mexican population. These variants are reported and classified in the ClinVar (PubMed) database and only some of them are recognized in the Online Mendelian Information in Men (OMIM). The present study included 37 patients, with 14 sporadic cases and 6 familial cases, with a total of 21 index cases. Next-generation sequencing was performed on a predesigned panel of 168 genes associated with heart disease and sudden death. The sequencing analysis revealed twelve (57%) pathogenic or probably pathogenic variants, 9 of them were familial cases, managing to identify pathogenic variants in relatives without symptoms of the disease. At the molecular level, nine of the 12 variants (75%) were single nucleotide changes, 2 (17%) deletions, and 1 (8%) splice site alteration. The genes involved were MYH7 (25%), MYBPC3 (25%) and ACADVL, KCNE1, TNNI3, TPM1, SLC22A5, TNNT2 (8%). In conclusion; we found five variants that were not previously reported in public databases. It is important to follow up on the reclassification of variants, especially those of uncertain significance in patients with symptoms of the condition. All patients included in the study and their relatives received family genetic counseling.
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Cardiomiopatia Hipertrófica , Cardiopatias , Masculino , Humanos , Cardiomiopatia Hipertrófica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Morte Súbita , Mutação , Membro 5 da Família 22 de Carreadores de Soluto/genéticaRESUMO
A 93-year-old woman with a history of endometrial adenocarcinoma treated with surgery and pelvic radiotherapy that led to radicular stenosis in the sigma and acute biliary pancreatitis, without subsequent cholecystectomy. She attended the emergency department for abdominal pain, vomiting and abdominal distension, with metallic noises. An abdominal CT scan showed a gallbladder with cholelithiasis, in wide contact with the colonic framework and dilation of the colonic loops with hydro-aerial levels with a partially calcified image embedded in the known sigmoid stenosis, compatible with intestinal obstruction. Given the high surgical risk, colonoscopy was performed, which identified an impassable punctate stricture with a fibrous appearance. Pneumatic dilatation and subsequent removal of gallstones with biopsy forceps was performed, with an adequate evolution. While gallstone ileus is a rare condition that accounts for 5% of episodes of intestinal obstruction, its location in the colon is even rarer. It is usually managed surgically, with a significant impact on morbidity. This case is of interest because of the infrequent occurrence of obstruction secondary to these two concomitant causes and the possible usefulness of endoscopic treatment in patients at high surgical risk.
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Cálculos Biliares , Íleus , Obstrução Intestinal , Doenças do Colo Sigmoide , Feminino , Humanos , Idoso de 80 Anos ou mais , Cálculos Biliares/complicações , Constrição Patológica , Íleus/etiologia , Doenças do Colo Sigmoide/complicações , Obstrução Intestinal/etiologia , Colo SigmoideRESUMO
Intestinal failure (IF) is the inability of the gut to absorb necessary water, macronutrients, micronutrients, and electrolytes sufficient to sustain life and requiring intravenous supplementation or replacement. IF Types 1 and 2 are the initial phase of this condition and usually last for weeks to a few months. Type 3 IF (also known as chronic IF [CIF]) is a chronic and stable condition, usually irreversible, whose main treatment is home parenteral nutrition. CIF is a relatively rare condition, and its prevalence and different causes vary throughout the world. Due to its complexity, CIF requires a multidisciplinary team with experience in this field to achieve successful outcomes. This editorial aims to provide an overview of CIF in adults, emphasizing the challenges faced by clinicians when managing this rare entity, as well as outlining the role of the gastroenterologist.
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Enteropatias , Insuficiência Intestinal , Nutrição Parenteral no Domicílio , Adulto , Doença Crônica , Humanos , Enteropatias/epidemiologia , Nutrição Parenteral no Domicílio/efeitos adversos , PrevalênciaRESUMO
SARS-CoV2 infection and vaccination against this virus have been related to the development of autoimmune diseases. We report a case of autoimmune hepatitis (AIH) after SARS-COV2 vaccine. Male, 76 years old, with a history of hepatic cirrhosis secondary to primary biliary cholangitis (PBC), compensated, treated with ursodeoxycholic acid and obeticholic acid. The patient received the third dose of the SARS-CoV2 vaccine (BioNTech/Pfizer) in December 2021. In subsequent analytical control, the patient presented altered liver test, with elevation of ALT and AST. Ultrasound was performed, without alterations, and viral causes were ruled out. IgG elevation and positive antinuclear antibodies were observed. A liver biopsy was performed, with findings of intense interface and lobular hepatitis and areas of centrilobular necrosis. The inflammation was predominantly lymphoplasmacytic. The patient was diagnosed with AIH and initiated therapy with steroids and azathioprine, currently with an adequate response. AIH is an immune-mediated disease of uncertain etiology. Cases of AIH with SARS-CoV2 vaccination as a possible trigger have recently been published, with characteristics similar to ours. Some of them had a history of autoimmune pathology, such as this case (PBC). Therefore, it is suggested that vaccination can induce the development of autoimmune pathology in patients at risk. Our reported case reinforces the hypothesis of an association between AIH and the SARS-CoV2 vaccine.
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Vacinas contra COVID-19 , COVID-19 , Hepatite Autoimune , Cirrose Hepática Biliar , Idoso , Vacinas contra COVID-19/efeitos adversos , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/etiologia , Humanos , Cirrose Hepática Biliar/tratamento farmacológico , Masculino , RNA Viral/uso terapêutico , SARS-CoV-2RESUMO
As a consequence of axenic growth and the elimination of accompanying bacterial flora, Entamoeba histolytica virulence decreases rapidly, and pathogenicity is lost. This paper evaluated the impact of vitamin supplementation on the pathogenicity of E. histolytica. Growth of E. histolytica trophozoites, cultured axenically in PEHPS (a Spanish acronym for the main ingredients - casein peptone, liver, pancreas extract and bovine serum) medium, with or without vitamins, exhibited a similar growth rate. However, the vitamin-enriched PEHPS preparations expressed 2.65 times more haemolytic activity (at 60 min: 98 vs 48%, P < 0.05), 2.5 times more phospholipase A2 activity at 150 min of incubation and generated more hepatic abscesses (88 vs 60%, P = 0.05) than the preparations without vitamins. The haemolytic and phospholipase A2 activity for the PEHPS - V preparations were restored following vitamin supplementation with A and D. These data highlight, for the first time, that vitamins and specifically vitamin A and D were essential for the recovery of amoebic virulence, lost through axenic growth.
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Cultura Axênica , Meios de Cultura/análise , Entamoeba histolytica/patogenicidade , Vitaminas/administração & dosagem , Entamoeba histolytica/efeitos dos fármacos , Entamoeba histolytica/crescimento & desenvolvimento , Trofozoítos/efeitos dos fármacos , Trofozoítos/crescimento & desenvolvimento , Trofozoítos/patogenicidade , VirulênciaRESUMO
Chemical analysis of the crude extract of bacterial strain Bacillus amyloliquefaciens ELI149, which had been previously isolated from soil, resulted in the isolation and characterization of two known macrolactin derivatives, macrolactin A (1) and 7-O-succinyl macrolactin A (2). The structures of two compounds were assigned by 1D/2D NMR techniques. The two compounds were demonstrated antifungal activity against some important phytopathogens. However, the presence of the succinyl moiety at C-7 gives to the molecule more activity being the second compound more active than the first, showing for the first time, a structure/activity relationship. The cellular damage was also studied in two important phytopathogen fungi.
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Antifúngicos , Bacillus amyloliquefaciens , Antibacterianos/farmacologia , Antifúngicos/farmacologia , MacrolídeosRESUMO
This study examines whether the intake of a high-fat diet very early in life leads to changes in arterial pressure and renal function and evaluates whether the mechanisms involved in these changes are sex-dependent. Experiments were performed in male and female Sprague-Dawley rats fed a normal or high-fat diet from weaning to 4 mo of age. This exposure to a high-fat diet lead to an angiotensin II-dependent elevation in arterial pressure and to significant increments in fat abdominal volume and plasma leptin that were similar in both sexes. In addition, the angiotensin II-induced increment in renal vascular resistance was greater ( P < 0.05) in male (106 ± 14%) and female (97 ± 15%) rats fed a high-fat diet than in rats fed a normal-fat diet (51 ± 8%). However, the high-fat intake during early life induced increments in albuminuria, interleukin-6, and infiltration of CD3 lymphocytes in the renal parenchyma that were greater ( P < 0.05) in male than in female rats. Other sex-dependent differences in response to high-fat intake were that adiponectin levels only decreased in females (21%, P < 0.05), and renal NF-κB expression only increased in males (31%, P < 0.05). In summary, the early exposure to a high-fat diet leads to angiotensin II-dependent arterial pressure elevations and to increments in abdominal fat and in the renal sensitivity to angiotensin II that are similar in both sexes. However, the mechanisms involved in the renal changes associated with early exposure to a high-fat diet are different in males and females.
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Dieta Hiperlipídica/efeitos adversos , Hipertensão/etiologia , Nefropatias/etiologia , Rim/fisiopatologia , Obesidade/etiologia , Gordura Abdominal/fisiopatologia , Adipocinas/sangue , Adiposidade , Fatores Etários , Albuminúria/etiologia , Albuminúria/fisiopatologia , Angiotensina II/toxicidade , Animais , Pressão Arterial , Progressão da Doença , Feminino , Hipertensão/sangue , Hipertensão/fisiopatologia , Mediadores da Inflamação/sangue , Rim/metabolismo , Nefropatias/sangue , Nefropatias/fisiopatologia , Masculino , Obesidade/sangue , Obesidade/fisiopatologia , Ratos Sprague-Dawley , Fatores Sexuais , Fatores de TempoRESUMO
Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L(+) CD11b(+) DCs. Mice lacking the TSLP receptor deficient mice (tslpr(-/-) ) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4(+) and CD8(+) T cells was found in tslpr(-/-) mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr(-/-) mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication.
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Citocinas/metabolismo , Metapneumovirus/fisiologia , Infecções por Paramyxoviridae/metabolismo , Infecções por Paramyxoviridae/virologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Transdução de Sinais , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Linhagem Celular , Citocinas/genética , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Expressão Gênica , Humanos , Interleucina-33 , Interleucina-8/genética , Interleucina-8/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Metapneumovirus/efeitos dos fármacos , Camundongos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Ligante OX40/antagonistas & inibidores , Ligante OX40/genética , Ligante OX40/metabolismo , Infecções por Paramyxoviridae/tratamento farmacológico , Infecções por Paramyxoviridae/genética , Infecções por Paramyxoviridae/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Pneumonia Viral/patologia , Receptores de Citocinas/antagonistas & inibidores , Receptores de Citocinas/deficiência , Transdução de Sinais/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Replicação Viral , Linfopoietina do Estroma do TimoRESUMO
Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin to ceramide and phosphorylcholine. Sphingolipids are recognized as diverse and dynamic regulators of a multitude of cellular processes mediating cell cycle control, differentiation, stress response, cell migration, adhesion, and apoptosis. Bacterial SMases are virulence factors for several species of pathogens. Whole cell extracts of Mycobacterium tuberculosis strains H37Rv and CDC1551 were assayed using [N-methyl-(14)C]-sphingomyelin as substrate. Acidic Zn(2+)-dependent SMase activity was identified in both strains. Peak SMase activity was observed at pH 5.5. Interestingly, overall SMase activity levels from CDC1551 extracts are approximately 1/3 of those of H37Rv. The presence of exogenous SMase produced by M. tuberculosis during infection may interfere with the normal host inflammatory response thus allowing the establishment of infection and disease development. This Type C activity is different from previously identified M. tuberculosis SMases. Defining the biochemical characteristics of M. tuberculosis SMases helps to elucidate the roles that these enzymes play during infection and disease.
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Mycobacterium tuberculosis/enzimologia , Esfingomielina Fosfodiesterase/metabolismo , Concentração de Íons de HidrogênioRESUMO
This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P < 0.05). This reduction in renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 µg/min vs. 72 ± 8 µg/min; P < 0.05) COX2np-treated rats. Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.
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Envelhecimento/fisiologia , Angiotensina II/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Angiotensina II/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Hipertensão/fisiopatologia , Rim/metabolismo , Masculino , Proteinúria/metabolismo , Ratos , Ratos Sprague-Dawley , Caracteres SexuaisRESUMO
The importance of membrane-bound PGE synthase 1 (mPGES1) in the regulation of renal function has been examined in mPGES1-deficient mice or by evaluating changes in its expression. However, it is unknown whether prolonged mPGES1 inhibition induces significant changes of renal function when Na(+) intake is normal or low. This study examined the renal effects elicited by a selective mPGES1 inhibitor (PF-458) during 7 days in conscious chronically instrumented dogs with normal Na(+) intake (NSI) or low Na(+) intake (LSI). Results obtained in both in vitro and in vivo studies have strongly suggested that PF-458 is a selective mPGES1 inhibitor. The administration of 2.4 mg·kg(-1)·day(-1) PF-458 to dogs with LSI did not induce significant changes in renal blood flow (RBF) and glomerular filtration rate (GFR). A larger dose of PF-458 (9.6 mg·kg(-1)·day(-1)) reduced RBF (P < 0.05) but not GFR in dogs with LSI and did not induce changes of renal hemodynamic in dogs with NSI. Both doses of PF-458 elicited a decrease (P < 0.05) in PGE2 and an increase (P < 0.05) in 6-keto-PGF1α. The administration of PF-458 did not induce significant changes in renal excretory function, plasma renin activity, and plasma aldosterone and thromboxane B2 concentrations in dogs with LSI or NSI. The results obtained suggest that mPGES1 is involved in the regulation of RBF when Na(+) intake is low and that the renal effects elicited by mPGES1 inhibition are modulated by a compensatory increment in PGI2. These results may have some therapeutical implications since it has been shown that prolonged mPGES1 inhibition has lower renal effects than those elicited by nonsteroidal anti-inflammatory drugs or selective cyclooxygenase-2 inhibitors.
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Oxirredutases Intramoleculares/antagonistas & inibidores , Oxirredutases Intramoleculares/metabolismo , Rim/fisiologia , Circulação Renal/fisiologia , Sódio/farmacologia , Aldosterona/sangue , Animais , Benzoxazóis/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Cães , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Oxirredutases Intramoleculares/genética , Rim/efeitos dos fármacos , Piperidinas/farmacologia , Potássio/urina , Prostaglandina-E Sintases , Circulação Renal/efeitos dos fármacos , Sódio/administração & dosagem , Sódio/urina , Tromboxano B2/sangueRESUMO
BACKGROUND AND OBJECTIVES: The recent emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) Mycobacterium tuberculosis (MTB) strains have further complicated the control of tuberculosis (TB). There is an urgent need of new molecules candidates to be developed as novel, active, and less toxic anti-tuberculosis (anti-TB) drugs. Medicinal plants have been an excellent source of leads for the development of drugs, particularly as anti-infective agents. In previous studies, the non-polar extract of Diospyros anisandra showed potent anti-TB activity, and three monomeric and five dimeric naphthoquinones have been obtained. In this study, we performed bioguided chemical fractionation and the isolation of eight naphthoquinones from D. anisandra and their evaluation of anti-TB and cytotoxic activities against mammalian cells. METHODS: The n-hexane crude extract from the stem bark of the plant was obtained by maceration and liquid-liquid fractionation. The isolation of naphthoquinones was carried out by chromatographic methods and identified by gas chromatography and mass spectroscopy data analysis. Anti-TB activity was evaluated against two strains of MTB (H37Rv) susceptible to all five first-line anti-TB drugs and a clinical isolate that is resistant to these medications (pan-resistant, CIBIN 99) by measuring the minimal inhibitory concentration (MIC). Cytotoxicity of naphthoquinones was estimated against two mammalian cells, Vero line and primary cultures of human peripheral blood mononuclear (PBMC) cells, and their selectivity index (SI) was determined. RESULTS: Plumbagin and its dimers maritinone and 3,3'-biplumbagin showed the strongest activity against both MTB strains (MIC = 1.56-3.33 µg/mL). The bioactivity of maritinone and 3,3'-biplumbagin were 32 times more potent than rifampicin against the pan-resistant strain, and both dimers showed to be non-toxic against PBMC and Vero cells. The SI of maritinone and 3,3'-biplumbagin on Vero cells was 74.34 and 194.11 against sensitive and pan-resistant MTB strains, respectively. CONCLUSION: Maritinone and 3,3'-biplumbagin possess a very interesting potential for development as new drugs against M. tuberculosis, mainly resistant profile strains.
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Antituberculosos/farmacologia , Diospyros/química , Mycobacterium tuberculosis/efeitos dos fármacos , Naftoquinonas/farmacologia , Animais , Antituberculosos/isolamento & purificação , Antituberculosos/toxicidade , Células Cultivadas , Chlorocebus aethiops , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Naftoquinonas/isolamento & purificação , Naftoquinonas/toxicidade , Casca de Planta , Extratos Vegetais/farmacologia , Caules de Planta , Rifampina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Células VeroRESUMO
Coccidioidomycosis is a systemic granulomatosis caused by dimorphic fungi Coccidioides immitis, which are endemic of the San Joaquin Valley in California, USA, and C. posadasii found in the southwestern desert of the USA, Mexico, and South America. The primary cutaneous form is extremely infrequent. There have been 25 reported cases in literature, all of them in adults. This is the first case in an infant.
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Coccidioidomicose/diagnóstico , Dermatomicoses/microbiologia , Dermatoses Faciais/microbiologia , Dermatoses Faciais/diagnóstico , Humanos , Lactente , MasculinoRESUMO
Immune checkpoint inhibitors (ICIs) are an approved therapy for the management of various advanced neoplasms. Limited reviews focus on the influence of this therapy resulting in pancreatitis. This review discusses the relationship between ICIs and their effects on the pancreas, including the incidence of pancreatitis, immunotherapy, programmed cell death 1 (PD-1) receptors, driver mutations, programmed death ligand 1 (PD-L1), and immune-related adverse events. Additionally, it focuses on the clinical presentations, diagnosis, case studies, and mechanisms by which ICIs activate different pathways to cause pancreatitis. We conducted a comprehensive literature search using PubMed, Cochrane Library, and Google Scholar databases to identify relevant studies on ICI-associated pancreatitis. The review explores the incidence and epidemiology of ICI-induced pancreatitis, its clinical presentation, diagnostic criteria, and management strategies.The overall incidence of ICI-induced pancreatitis is estimated at 1-2%, with higher rates observed in combination therapy. Clinical presentations range from asymptomatic enzyme elevations to severe pancreatitis. Diagnosis relies on a combination of clinical symptoms, elevated pancreatic enzymes, and imaging findings, with MRI and endoscopic ultrasound showing promise in early detection. Management strategies include IV fluid administration, pain control, and nutritional support. The efficacy of corticosteroids remains controversial, and alternative immunosuppressants are being explored for steroid-refractory cases. Long-term monitoring is crucial due to the risk of chronic pancreatitis and pancreatic insufficiency. This review highlights the need for further research to elucidate the exact mechanisms of ICI-associated pancreatic injury, develop predictive biomarkers, and refine treatment protocols. As ICI use continues to expand, a thorough understanding of this adverse event is essential for optimizing patient care and outcomes in cancer immunotherapy.
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It is known that cyclooxygenase-2 (COX-2) inhibition elicits significant renal hemodynamics alterations when sodium intake is low. However, the mechanisms involved in these renal changes are not well known. Our objective was to evaluate the role of angiotensin II and 5-lipooxygenase-derived metabolites in the renal effects induced by prolonged COX-2 inhibition when sodium intake is low. Conscious dogs were treated during 7 days with a COX-2 inhibitor (1 mg·kg·d, SC75416), and either a vehicle, an AT1 receptor antagonist (0.4 mg · kg · d, candesartan) or a selective 5-lipooxygenase inhibitor (PF-150, 20 and 60 mg · kg · d). The administration of SC75416 alone induced significant changes in renal blood flow (219 ± 14 to 160 ± 10 mL/min), glomerular filtration rate (51 ± 2 to 42 ± 3 mL/min), and plasma potassium (pK) (4.3 ± 0.1 to 4.6 ± 0.1 mEq/L). Similar decrements in renal blood flow (27%) and glomerular filtration rate (20%) and a similar increment in pK (7%) were found when SC75416 was administered in candesartan-pretreated dogs. However, SC75416 administration did not elicit significant changes in renal hemodynamics and pK in dogs pretreated with each dose of PF-150. Our data suggest that leukotrienes but not angiotensin II are involved in the renal effects induced by COX-2 inhibition when sodium intake is low.
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Angiotensina II/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dieta Hipossódica , Leucotrienos/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Benzimidazóis/farmacologia , Benzopiranos/farmacologia , Compostos de Bifenilo , Ciclo-Oxigenase 2/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Cães , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Rim/metabolismo , Inibidores de Lipoxigenase/administração & dosagem , Inibidores de Lipoxigenase/farmacologia , Piranos/administração & dosagem , Piranos/farmacologia , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Circulação Renal/efeitos dos fármacos , Tetrazóis/farmacologiaRESUMO
Childhood obesity predicts adult obesity and may increase the lifetime risk of adverse health outcomes. Obesity is characterized by oxidative stress that can induce DNA damage; however, studies of childhood and adolescent obesity are scarce. We investigated DNA damage due to obesity in Mexican children using the chromatin dispersion test (CDT). We evaluated DNA damage to peripheral lymphocytes of 32 children grouped according to body mass index as normal weight (controls), overweight and obese groups using guidelines from the Centers for Disease Control (CDC). We found that the greatest DNA damage occurred in cells of obese children compared to normal weight and overweight children. Our findings support preventive action to obviate adverse health outcomes due to obesity.
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Obesidade Infantil , Adulto , Humanos , Criança , Adolescente , Obesidade Infantil/genética , Sobrepeso , Índice de Massa Corporal , Dano ao DNA , Cromatina/genéticaRESUMO
Introduction: Hispanic immigrants are a fast-growing population in the United States of America (USA) that disproportionately suffer from chronic diseases. Despite the increasing prevalence of obesity in Latin-American countries, only a few studies have examined the onset of chronic diseases in Mexican and Central American migrants in Mexico. Objective: The objective of this study is to determine the prevalence of obesity, diabetes, and hypertension in Central American immigrants who are in the process of traveling through northeastern Mexico to the United States. Methods: An observational, descriptive, cross-sectional study was conducted among migrants, mostly Central Americans. Migrants who agreed to participate in the study were interviewed face-to-face by researchers to obtain their sociodemographic data. To obtain the prevalence, many health indicators related to obesity, diabetes, and hypertension, including weight, height, fasting glucose, and blood pressure, were measured. Results: In total, 520 migrants were interviewed; sociodemographic data indicated that most participants were men (76%), from Honduras (72.6%), single (61.2%), and have elementary level of education (48.6%). The somatometric evaluation revealed that 28.9% were diagnosed as overweight, 10.7% with obesity, and 3.3% with malnutrition. Of less prevalence, 8.8% were detected with hypertension and 4.6% had fasting hyperglycemia. The mean participant age was 29.11 ± 10.00 years. For each participant, the average weight was 66.72 ± 13.09 kg; the average height was 1.64 ± 0.08 m; the average body mass index (BMI) was 24.59 ± 4.32; the mean systolic and diastolic pressures were 116.26 ± 15.13 and 74 ± 9.65, respectively; and the average glycemia was 100.97 ± 21.99. El Salvador showed the highest proportion of people with diabetes (14.7%). Women who participated in this study had a higher proportion of obesity (23.4%, p = 0.02) and overweight (36.2%) than men (8.4 and 29.2%, respectively). People from Mexico, Nicaragua, and Honduras reported a high prevalence of overweight participants (63.6, 47.4, and 30.7%, respectively), while people from El Salvador and Nicaragua had a high prevalence of obese participants (23.5 and 21.1%, respectively). Conclusion: We found significant differences in the rates of obesity, diabetes, and hypertension between groups of Central American migrants and their place of origin, age, educational level, and gender. Our findings highlight the importance of exploring differences within groups of Central American migrants traveling through northeastern Mexico to the United States, which may explain several health indicators.
Assuntos
Diabetes Mellitus , Emigrantes e Imigrantes , Hipertensão , Masculino , Humanos , Feminino , Estados Unidos , Adulto Jovem , Adulto , México/epidemiologia , Sobrepeso/epidemiologia , Estudos Transversais , Prevalência , Fatores de Risco , Obesidade/epidemiologia , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Doença CrônicaRESUMO
Livestock manure management systems can be significant sources of nitrous oxide (N2 O), methane (CH4 ), and ammonia (NH3 ) emissions. Many studies have been conducted to improve our understanding of the emission processes and to identify influential variables in order to develop mitigation techniques adapted to each manure management step (animal housing, outdoor storage, and manure spreading to land). The international project DATAMAN (http://www.dataman.co.nz) aims to develop a global database on greenhouse gases (N2 O, CH4 ) and NH3 emissions from the manure management chain to refine emission factors (EFs) for national greenhouse gas and NH3 inventories. This paper describes the housing and outdoor storage components of this database. Relevant information for different animal categories, manure types, livestock buildings, outdoor storage, and climatic conditions was collated from published peer reviewed research, conference papers, and existing databases published between 1995 and 2021. In the housing database, 2024 EFs were collated (63% for NH3 , 19.5% for CH4 , and 17.5% for N2 O). The storage database contains 654 NH3 EFs from 16 countries, 243 CH4 EFs from 13 countries, and 421 N2 O EFs from 17 countries. Across all gases, dairy cattle and swine production in temperate climate zones are the most represented animal and climate categories. As for the housing database, the number of EFs for the tropical climate zone is under-represented. The DATAMAN database can be used for the refinement of national inventories and better assessment of the cost-effectiveness of a range of mitigation strategies.