Impact on the Clinical Evolution of Patients with COVID-19 Pneumonia and the Participation of the NFE2L2/KEAP1 Polymorphisms in Regulating SARS-CoV-2 Infection.

In patients with severe pneumonia due to COVID-19, the deregulation of oxidative stress is present. Nuclear erythroid factor 2 (NRF2) is regulated by KEAP1, and NRF2 regulates the expression of genes such as NFE2L2-KEAP1, which are involved in cellular defense against oxidative stress. In this study, we analyzed the participation of the polymorphisms of NFE2L2 and KEAP1 genes in the mechanisms of damage in lung disease patients with SARS-CoV-2 infection. Patients with COVID-19 and a control group were included. Organ dysfunction was evaluated using SOFA. SARS-CoV-2 infection was confirmed and classified as moderate or severe by ventilatory status and by the Berlin criteria for acute respiratory distress syndrome. SNPs in the gene locus for NFE2L2, rs2364723C>G, and KEAP1, rs9676881A>G, and rs34197572C>T were determined by qPCR. We analyzed 110 individuals with SARS-CoV-2 infection: 51 with severe evolution and 59 with moderate evolution. We also analyzed 111 controls. Significant differences were found for rs2364723 allele G in severe cases vs. controls (p = 0.02); for the rs9676881 allele G in moderate cases vs. controls (p = 0.04); for the rs34197572 allele T in severe cases vs. controls (p = 0.001); and in severe vs. moderate cases (p = 0.004). Our results showed that NFE2L2 rs2364723C>G allele G had a protective effect against severe COVID-19, while KEAP1 rs9676881A>G allele G and rs34197572C>T minor allele T were associated with more aggressive stages of COVID-19.

The Role of Bile Acids in Glucose Metabolism and Their Relation with Diabetes.

Bile acids (BAs), the end products of cholesterol catabolism, are essential for the absorption of lipids and fat-soluble vitamins; but they have also emerged as novel signaling molecules that act as metabolic regulators. It has been well described that the enterohepatic circulation, a nuclear (FXR) and a cytoplasmic (TGR5/M-BAR) receptor aid in controlling hepatic bile acid synthesis. Modulating bile acid synthesis greatly impacts in metabolism, because these receptors also are implicated in glucose, lipid, and energy expenditure. Recent studies had revealed the way these receptors participate in regulating gluconeogenesis, peripheral insulin sensitivity, glycogen synthesis, glucagon like peptide 1 (GLP-1) and insulin secretion. Nowadays, it is demonstrated that enhancing bile acid signaling in the intestine contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery on glucose homeostasis. This paper discusses the role of bile acid as regulators of glucose metabolism and their potential as therapeutic targets for diabetes.

The Role of Bile Acids in Glucose Metabolism and Their Relation with Diabetes.

Bile acids (BAs), the end products of cholesterol catabolism, are essential for the absorption of lipids and fat-soluble vitamins; but they have also emerged as novel signaling molecules that act as metabolic regulators. It has been well described that the enterohe-patic circulation, a nuclear (FXR) and a cytoplasmic (TGR5/M-BAR) receptor aid in controlling hepatic bile acid synthesis. Modulating bile acid synthesis greatly impacts in metabolism, because these receptors also are implicated in glucose, lipid, and energy expenditure. Recent studies had revealed the way these receptors participate in regulating gluconeogenesis, peripheral insulin sensitivity, glycogen synthesis, glucagon like peptide 1 (GLP-1) and insulin secretion. Nowadays, it is demonstrated that enhancing bile acid signaling in the intestine contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery on glucose homeos-tasis. This paper discusses the role of bile acid as regulators of glucose metabolism and their potential as therapeutic targets for diabetes.

Low-Normal Thyroid Function Is Not Associated with Either Non-Alcoholic Fatty Liver Disease or with Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND: The association of low-normal thyroid function (LNTF) with non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) is controversial; thus, the aim of this study is to determine this association. METHODS: NAFLD was evaluated by controlled attenuation parameter of transient elastography. Patients were classified by MAFLD criteria. LNTF was defined as TSH levels of 2.5 to 4.5 mIU/L and were divided into three different cut-off points (>4.5 to 5.0, >3.1, and >2.5 mIU/L). Associations between LNTF, NAFLD, and MAFLD were evaluated by univariate and multivariate logistic regression analyses. RESULTS: A total of 3697 patients were included; 59% (n = 2179) were male, and median age and body mass index were 48 (43-55) years and 25.9 (23.6-28.5) kg/m2, respectively, and 44% (n = 1632) were diagnosed with NAFLD. THS levels of 2.5 and 3.1 showed significant associations with the presence of NAFLD and MAFLD; however, LNTF did not show an independent association with the presence of NAFLD or MAFLD in multivariate analysis. According to different cut-off points, patients with LNTF presented similar risks for NAFLD as the general population. CONCLUSION: LNTF is not associated with NAFLD or MAFLD. Patients with high LNTF are equally at risk for NAFLD as the general population.

Alteration in the Lipid Profile and the Desaturases Activity in Patients With Severe Pneumonia by SARS-CoV-2.

The kidnapping of the lipid metabolism of the host's cells by severe acute respiratory syndrome (SARS-CoV-2) allows the virus to transform the cells into optimal machines for its assembly and replication. Here we evaluated changes in the fatty acid (FA) profile and the participation of the activity of the desaturases, in plasma of patients with severe pneumonia by SARS-CoV-2. We found that SARS-CoV-2 alters the FA metabolism in the cells of the host. Changes are characterized by variations in the desaturases that lead to a decrease in total fatty acid (TFA), phospholipids (PL) and non-esterified fatty acids (NEFAs). These alterations include a decrease in palmitic and stearic acids (p ≤ 0.009) which could be used for the formation of the viral membranes and for the reparation of the host's own membrane. There is also an increase in oleic acid (OA; p = 0.001) which could modulate the inflammatory process, the cytokine release, apoptosis, necrosis, oxidative stress (OS). An increase in linoleic acid (LA) in TFA (p = 0.03) and a decreased in PL (p = 0.001) was also present. They result from damage of the internal mitochondrial membrane. The arachidonic acid (AA) percentage was elevated (p = 0.02) in the TFA and this can be participated in the inflammatory process. EPA was decreased (p = 0.001) and this may decrease of pro-resolving mediators with increase in the inflammatory process. The total of NEFAs (p = 0.03), PL (p = 0.001), cholesterol, HDL and LDL were decreased, and triglycerides were increased in plasma of the COVID-19 patients. Therefore, SARS-CoV-2 alters the FA metabolism, the changes are characterized by alterations in the desaturases that lead to variations in the TFA, PL, and NEFAs profiles. These changes may favor the replication of the virus but, at the same time, they are part of the defense system provided by the host cell metabolism in its eagerness to repair damage caused by the virus to cell membranes.

Antioxidants and pentoxifylline as coadjuvant measures to standard therapy to improve prognosis of patients with pneumonia by COVID-19.

The type 2 coronavirus causes severe acute respiratory syndrome (SARS-CoV-2) and produces pneumonia with pulmonary alveolar collapse. In some cases it also causes sepsis and septic shock. There is no specific treatment for coronavirus disease 2019 (COVID-19). Vitamin C (Vit C), Vitamin E (Vit E), N-acetylcysteine (NAC) and Melatonin (MT) increase the intracellular content of GSH, kidnap free radicals and protect DNA, proteins in the cytosol and lipids in cell membranes. Pentoxifylline (Px) has anti-inflammatory activities. Here we evaluate the effect of Vit C, Vit E, NAC, and MT plus Px in COVID-19 patients with moderate and severe pneumonia. 110 patients of either sex were included. They were divided into five groups with 22 patients each. Group 1 received Vit C + Px, group 2 Vit E + Px, group 3 NAC + Px, group 4 MT + Px, and group 5 only Px. Oxidative stress (OS) markers such as lipid peroxidation (LPO) levels, total antioxidant capacity (TAC) and nitrites (NO2 -) were evaluated in plasma. The antioxidant therapy improved the survival scores including the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and chronic Health Evaluation II (Apache II), the Simplified Acute Physiology Score II (SAPS II), the Critical Illness Risk Score, Launched during COVID-19 crisis (COVIDGRAM) and the Glasgow Coma Scale (GCS). We found that LPO (p≤0.04) and inflammation markers such as interleukin-6 (IL-6, p≤ 0.01), C reactive protein (CRP, p ≤ 0.01) and procalcitonin (PCT, p ≤ 0.05) were elevated. TAC (p ≤ 0.03) and NO2 - (p ≤ 0.04) found themselves diminished in diminished in COVID-19 patients upon admission to the hospital. The different antioxidants reversed this alteration at the end of the treatment. The treatment with antioxidant supplements such as Vit C, E, NAC, and MT plus Px could decelerate the aggressive and lethal development of COVID-19. Antioxidant therapy can be effective in this pandemia since it improves the survival scores including SOFA, Apache II, SAPS II, COVIDGRAM, GCS by lowering the LPO, IL-6, CRP, PCT and increasing systemic TAC and NO2 -.

PREVALENCE OF AUTOIMMUNE THYROIDITIS AND THYROID DYSFUNCTION IN HEALTHY ADULT MEXICANS WITH A SLIGHTLY EXCESSIVE IODINE INTAKE.

OBJECTIVE: the purpose of this study was to evaluate the prevalence of autoimmune thyroiditis and thyroid dysfunction in healthy individuals with no previously known thyroid disease, in an urban area of Mexico City. SUBJECTS AND METHODS: the study was conducted on volunteers with no known thyroid disease. We recruited 427 subjects among the hospital's medical and administration personnel. All underwent thyroid ultrasound (US) and TSH, free T4 (FT4), total T3 (TT3), thyroid anti-peroxidase (TPOAb) and anti-thyroglobulin (TgAb) antibodies were measured. Hypoechogenicity and thyroid volume were determined by US. Urinary iodine (UI) excretion was also measured. RESULTS: the frequency of autoimmune thyroiditis was 8.4% (36/427) and women were most commonly affected than men (11.6 vs. 4.3% respectively, P = 0.008); when including cases of atrophic thyroid, the frequency increased to 15.7% (67/427). Clinical hypothyroidism was detected in 1.2% (5/427) and it was sub-clinical in 5.6% of individuals. A goiter was present in 5.9% (25/427) of volunteers. Median UI was 267 µg/L, (IQR 161.3 - 482.5). CONCLUSIONS: in spite of our study's limitations, the frequency of autoimmune thyroiditis is clearly elevated in the studied population. Further studies are necessary in order to define the prevalence of autoimmune thyroid disease as well as the current iodine nutritional status in our country.

Objetivo: el objetivo del presente estudio fue evaluar la prevalencia de tiroiditis autoinmune y disfunción tiroidea en individuos sanos sin enfermedad tiroidea conocida, de un área urbana de la ciudad de México. Material y métodos: el estudio se realizó en voluntarios sin enfermedad tiroidea conocida. Se reclutaron 427 individuos entre personal médico y administrativo del hospital. A todos se les realizó ultrasonido (US) tiroideo, TSH, T4 libre (FT4), T3 total (TT3), anticuerpos anti-peroxidasa tiroidea (TPOAb) y anti tiroglobulina (TgAb). Dentro de la evaluación por US se incluyó la hipoecogenicidad y el volumen tiroideo. También se midió la excreción urinaria de yodo (UI). Resultados: la frecuencia de tiroiditis autoinmune fue de 8,4% (36/427), las mujeres fueron más afectadas que los hombres (11,6 vs. 4,3%, respectivamente, P = 0,008), cuando se sumó la tiroides atrófica, esta frecuencia se elevó al 15,7% (67/427) de los estudiados. El hipotiroidismo clínico fue detectado en el 1,2% (5/427) y el subclínico en el 5,6%. El hipertiroidismo clínico solo se observó en el 0,5% (2/427) y el subclínico en el 1,9%. El bocio se identificó en el 5,9% (25/427) de los voluntarios. La mediana de la UI fue de 267 µg/L, RIQ (161,3 ­ 482,5). Conclusiones: a pesar de las limitaciones de nuestro estudio, es clara la frecuencia incrementada de tiroiditis autoinmune en la población estudiada. Son necesarios más estudios que definan tanto la prevalencia de enfermedad tiroidea autoinmune como el estatus nutricional de yodo actual en nuestro país.

Determination of thyrotropin reference values in an adult Mexican population.

BACKGROUND AND OBJECTIVE: The upper limit of TSH reference level is controversial. The purpose of our study was to determine TSH reference values in a Mexican population in accordance with the National Academy of Clinical Biochemistry (NACB) criteria and in correlation with thyroid ultrasound (US) examination. PATIENTS AND METHODS: The study was conducted in volunteers with no known thyroid disease. We recruited 482 subjects, most of them medical or administrative staff from our hospital. They answered a questionnaire on demographic data, family history, co-morbidities, and drug use. Their thyroid hormone levels and thyroid antibodies were determined, and a complete physical examination and thyroid US were performed. The population used to establish the TSH reference intervals was selected according to the NACB criteria and their normal thyroid structural and echogenic characteristics in US examination. RESULTS: Among 482 subjects (209 males) with a median age of 26 years, prevalence rates of TPOAb and TgAb were 9.3% and 10.3% respectively. Mean TSH level in the overall population was 1.90±1.94, with a 97.5th percentile of 6.76 mIU/L. The reference population was limited to 282 subjects (41.5% were excluded) with a mean TSH of 1.86±1.63 and a 97.5th percentile of 4.88 mIU/L. No sex difference was found (p=0.287). Median urinary iodine level in the reference population was 267 µg/L IQR (161.3-482.5). CONCLUSIONS: The TSH reference interval in the reference population was 0.71 (CI 0.65-0.77) to 4.88 mIU/L (CI 4.5-5.3); these limits may be influenced by iodine nutritional status in this population.

Renal tuberculosis.

BACKGROUND: tuberculosis (TB) is a disease with a high incidence and prevalence worldwide. Renal TB is the second most common extrapulmonary form of TB. The purpose of this report is to present the case of a patient with renal TB in order to emphasize the importance of this disease. CLINICAL CASE: we report the case of a 30-year-old female who presented with fever, cough, diaphoresis and an abdominal right flank mass. Right hydronephrosis, dilated collector system and loss of renal function were documented. A right nephrectomy was performed. Histopathological exam revealed acid-fast mycobacteria, granulomas and multinucleated Langhans-type giant cells. Renal TB was diagnosed and anti-TB treatment was initiated. CONCLUSIONS: renal TB is a disease whose incidence has increased in relation to the TB epidemic. Renal TB should be considered in the evaluation of renal masses.