Revista De Investigacion Clinica-Clinical and Translational Investigation最新文献

Alcohol consumption has been linked to numerous pathologic conditions, including infectious diseases and several types of cancer. Alcohol exerts its modulatory effects on the immune system (IS) in a dose- and time-dependent manner. Numerous studies indicate that these alterations affect responses such as peripheral inflammation or decreased antibody production and promote chronic inflammation, leading to cell death. The molecular mechanisms underlying these effects involve generating an oxidative tissue environment, producing cell damage-associated molecular patterns (DAMPs), and activating pattern recognition receptors. In particular, toll-like receptors and their signaling system emerge as central elements whose activity is altered by alcohol intake. There is also some epidemiological evidence demonstrating the causal role of alcohol in the development of various types of cancer, such as head-and-neck cancer, esophageal cancer, colorectal cancer, liver cancer, and breast cancer. Most recent evidence suggests that factors related to alcohol consumption and cancer include increased levels of acetaldehyde, production of reactive oxygen species, alteration in DNA methylation, and modifications in retinoid metabolism. In addition, changes associated with alcohol use on the IS and intestinal microbiota may favor the growth of some types of tumors.

This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.

Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New psychoactive opioids (NPOs) are classified in the internationally recognized new psychoactive substances (NPSs) category. This group comprises compounds that may have been synthesized decades ago but appeared only recently in the illicit drug market. Such is the case of fentanyl, fentanyl analogs, and non-fentanyl opioids. Most NPOs have effects similar to morphine, including euphoria and analgesia, and can produce fatal respiratory depression. Here, we present an overview of the systemic and molecular effects of main NPOs, their classification, and their pharmacological properties. We first review the fentanyl group of NPOs, including the four compounds of clinical use (fentanyl, alfentanil, sufentanil, and remifentanil) and the veterinary drug carfentanil. We also provide essential information on non-medical fentanyl analogs and other synthetic opioids such as brorphine, etonitazene, and MT-45, used as adulterants in commonly misused drugs. This paper also summarizes the scarce literature on the use of NPOs in Mexico. It concludes with a brief review of the challenges to prevention and treatment posed by NPOs and some recommendations to face them.

Background: Recipients of a related haploidentical stem cell transplant (haplo-SCT) can have preformed antibodies to HLA donor’s antigens.

Objective: The aim of the study was to evaluate the engraftment rate and major clinical associations of anti-HLA donor-specific antibodies (DSA) at two mean fluorescence intensity (MFI) thresholds in recipients of an outpatient haplo-SCT.

Methods: Seventy haplo-HCT recipients were analyzed. A virtual crossmatch was performed using the donor HLA typing and the recipient’s anti-HLA DSA test results. Data for anti-HLA-A, -B, -C, and -DR were analyzed. Recipients with DSA ≥ 500 MFI were considered positive, and those with < 500 were considered negative; the same was adopted for MFI ≥ 1000.

Results: Post-transplant infection was higher in recipients with DSA ≥ 500 MFI (84.6%, p = 0.041). First-year mortality was higher in DSA-positive patients ≥ 500 MFI, p = 0.004, and DSA ≥ 1000 MFI, p = 0.022, than in DSA-negative recipients. Graft failure in the first 100 days was not associated with DSA ≥ 500 or ≥ 1000 MFI. There was no difference in acute (a-GVHD) or chronic (c-GVHD) graft versus host disease between DSA-positive and negative patients.

Conclusions: There was no association of anti-HLA DSA at MFI ≥ 500 and ≥ 1000 with graft failure, however, increased infection and 1st-year mortality were documented in related haplo-HCT at the MFI cutoffs studied.

Unassigned: In the 1970s, acute peritoneal dialysis (PD) was widely accepted for the treatment of acute kidney injury (AKI), but this practice has declined in favor of extracorporeal therapies, mainly in developed world. The lack of familiarity with the use of PD in critically ill patients has also led to a lack of use even among those receiving maintenance PD. Renewed interest in the use of PD for AKI therapy has emerged due to its increasing use in low- and middle-income countries due to its lower cost and minimal infrastructural requirements. In high-income countries, the coronavirus disease 2019 pandemic saw PD for AKI used early on, where many critical care units were in crisis and relied on PD use when resources for other AKI therapy modalities were limited. In this review, we highlight the advantages and disadvantages of PD in AKI patients and indications and contraindications for its use. We also provide an overview of advances to support PD treatment during AKI, discussing PD access, PD prescription, complications related to PD, and its use in particular clinical conditions. (Rev Invest Clin. 2023;75(6):327-36).

The tobacco epidemic has been one of the biggest public health threats, and smoking is one of the world's largest preventable causes of premature death. An estimated 15.4% of all deaths in the world are attributable to tobacco smoking. The present review aims to describe addiction to tobacco smoking and vaping. Tobacco and vaping devices contain nicotine, a highly addictive drug, which explains why smoking is so prevalent and persistent. Electronic cigarettes are a group of novel nicotine or tobacco products that have rapidly gained popularity in recent years. Electronic cigarette devices allow for the use of other drugs, including THC, while the lax regulation may allow for the introduction of toxic compounds that can lead to acute or subacute toxicity, such as the e-cigarette- or vaping-associated lung injury that has been linked to vitamin E acetate. In addition, regular vapers and heated tobacco devices emit toxins, although at lower concentrations than burned tobacco. However, more and more side effects have been identified. No new effective treatment for nicotine addiction has been developed recently, despite its huge adverse impact on overall health and other outcomes. As for the primary line of medications, the last one started in 2006, the varenicline, demonstrating a low interest in developing new medications against smoking, an unacceptable state of affairs, given the huge impact of smoking on morbidity and mortality.

Background: Insulin resistance (IR) contributes to the development of hypertension and mediated organ damage (HMOD) through various mechanisms.

Objectives: The objective of the study was to assess the diagnostic performance of the triglyceride-glucose (TyG) index, a surrogate marker of IR, in predicting the presence and severity of HMOD in newly diagnosed untreated hypertensive patients from an academic training and research hospital

Methods: The study included 438 patients with newly diagnosed, untreated hypertension. The control group comprised normotensive individuals matched on a 1:1 ratio based on age, gender, body mass index, and smoking using the nearest neighbor method. The presence of HMOD was defined by renal damage (microalbuminuria > 30 mg/day or proteinuria > 150 mg/day), vascular damage (carotid intima-media thickness > 0.9 mm or presence of plaque), or cardiac damage (left ventricular mass index > 95 g/m2 in women and > 115 g/m2 in men). The severity of HMOD was considered as single-, two-, or triple-organ damage.

Results: TyG index values were higher in the hypertensive group than the normotensive group. An increased TyG index was independently associated with HMOD (OR: 1.33, p < 0.001). The TyG index exhibited gradually increasing threshold values for distinguishing patients with single-organ HMOD (> 8.8 with 77.8% sensitivity and 74.3% specificity), two-organ HMOD (> 9.1 with 77.6% sensitivity and 71.4% specificity), and triple-organ HMOD (> 9.4 with 71.5% sensitivity and 87.7% specificity).

Conclusions: In newly diagnosed hypertensive patients, the TyG index exhibits significant diagnostic performance in predicting multiple-organ damage beyond the presence of HMOD. Since the detection of multiple-organ HMOD requires a multidisciplinary approach, the TyG index can serve as a simple and inexpensive screening tool.

Background: MicroRNA-421 (miR-421) has been implicated in hepatocellular carcinoma (HCC), but its potential mechanism in HCC remains unclear.

Objectives: The study aimed to study the potential mechanism of miR-421 in HCC which is necessary.

Methods: The downstream target genes of miR-421 were screened in HCC tissues and cells using miDIP, Targetscan, and starBase databases. Differential analysis, survival analysis, and Pearson correlation analysis were performed between miR-421 and its downstream target genes. Quantitative reverse transcription polymerase chain reaction and western blot were used to assay RNA and protein levels of 4-aminobutyrate aminotransferase (ABAT) and epithelial-mesenchymal transition (EMT)-related proteins. Cell-based assays, including CCK-8, wound healing, transwell, flow cytometry, and metabolic measurements, were implemented to assess proliferation, migration, invasion, cell cycle, and apoptosis of HCC cells with different treatments. Dual-luciferase assay was utilized to detect the targeting relationship between miR-421 and ABAT.

Results: miR-421 level was elevated in HCC tissues and cells, and low miR-421 expression hindered phenotype progression of HCC cells. ABAT was identified as a direct target of miR-421 in HCC cells, and miR-421 could inhibit ABAT expression. Rescue assay revealed that miR-421 promoted HCC cell tumorigenesis progress and affected cell metabolic remodeling through down-regulating ABAT.

Conclusion: The miR-421/ABAT regulatory axis promoted HCC cell tumorigenesis progress, highlighting its potential as a therapeutic target for HCC.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide and is highly prevalent in Mexico, as 10.2% of the adult population harbors this condition. T2DM is usually associated with cardiovascular comorbidities, including arrhythmias. Metabolic impairment is one of the mechanisms that contribute to tissue remodeling that affects atrial structure, and concomitant, the cardiac conduction system, both could result in atrial fibrillation (AF). AF is estimated to affect more than a half million Mexicans, and its incidence is expected to keep rising. According to national registries, T2DM is present in 28.4% of Mexican patients with AF and the coexistence of both diseases is associated with a higher risk of stroke. In clinical practice, the CHA₂DS₂-VASc risk score is useful for stroke risk stratification in patients with AF to facilitate the adequate use of anticoagulation therapy. T2DM is among the items of the CHA₂DS₂-VASc score because it correlates with an intrinsic prothrombotic state. In this narrative review, we present information that highlights the need for optimal glucose control and adequate anticoagulation in subjects with T2DM and AF.