Juan Gerardo Reyes-García

Instituto Politécnico Nacional

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Héctor Isaac Rocha‐González

Instituto Politécnico Nacional

Juan Carlos Huerta‐Cruz

Instituto Nacional de Enfermedades Respiratorias

Ashuin Kammar‐García

Instituto Nacional de Pediatria

Francisco Javier Flores‐Murrieta

Instituto Nacional de Enfermedades Respiratorias

Samuel Canizales‐Quinteros

Universidad Nacional Autónoma de México

Miriam del Carmen Carrasco‐Portugal

Instituto Nacional de Enfermedades Respiratorias

Juan Rodríguez‐Silverio

Instituto Politécnico Nacional

Lina Marcela Barranco‐Garduño

Instituto Nacional de Enfermedades Respiratorias

Francisco Barajas‐Olmos

National Institute of Genomic Medicine

Martha Guevara‐Cruz

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

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Instituto Politécnico Nacional

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Universidad Nacional Autónoma de México

National Institute of Genomic Medicine

Secretaria de Salud

Instituto de Medicina Genómica

Mexican Social Security Institute

National Legal Medicine Institute

Instituto Nacional de Enfermedades Respiratorias

Center for Research and Advanced Studies of the National Polytechnic Institute

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Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions

Genes (2022)

Itzel G. Salazar-Valencia Hugo Villamil‐Ramírez Francisco Barajas‐Olmos Martha Guevara‐Cruz Luis Macías‐Kauffer

The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5–9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: −4.0 kg (−2.9%) in patient 1, and −1.8 kg (−1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (−2.9 kg; −2.8%). Phentermine treatment produced similar weight loss in six carriers (−12.7 kg; 15.5%) and 18 non-carriers (−11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.

Phentermine

Melanocortin 4 receptor

10.3390/genes13122267

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Citations (4)

Combined First Month Body Weight Loss and Development of Tolerance as Predictors of 6-Month Efficacy of Mazindol in Mild and Moderate Obese Subjects

Journal of Clinical Medicine (2022)

Juan Carlos Huerta-Cruz Héctor Isaac Rocha-González Ashuin Kammar‐García Samuel Canizales‐Quinteros Lina Marcela Barranco‐Garduño

The weight loss response to anti-obesity drugs is highly variable and poorly understood, which does not allow us to know, in advance, in which subjects the drug will be effective and in which it will not. The objective of this study was to explore the body weight reduction in kilograms in the first month (1mo-BWRkg) and the development of tolerance as predictors of 6-month efficacy for treatment with 1 mg mazindol twice a day. One hundred ninety-six obese subjects were individually or jointly analyzed. Approximately 60% of subjects developed tolerance to mazindol and achieved increasing proportional levels of 6-month efficacy according to 1mo-BWRkg intervals (<1 kg, 1 to <2 kg, 2 to <4 kg and ≥4 kg). Both moT and 1mo-BWRkg were significantly correlated with the mean percentage body weight reduction (BWR%) after 6-months of treatment. The qualitative analysis of both predictors on the progressive efficacy of mazindol was used to classify patients according to expected efficacy (inefficient, slightly effective, partially effective, or fully effective), based on the mean percentage efficacy and the number of subjects reaching a BWR% of <5%, 5 to <10%, 10 to <15% or ≥15%. In conclusion, combined 1mo-BWRkg and moT were early predictors for the progressive efficacy of 6-month mazindol anti-obesity therapy. This finding represents progress in predictive, preventive, and personalized medicine which could serve for estimating the expectations of individual efficacy with the use of the drug. and highlights the basic principle of personalized medicine, “one size does not fit all”.

Mazindol

Efficacy

Clinical efficacy

10.3390/jcm11113211

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Citations (2)

Editorial: Precision treatments for patients with obesity

Frontiers in Medicine (2024)

Héctor Isaac Rocha-González Ashuin Kammar‐García Ariana Vargas‐Castillo Juan Gerardo Reyes-García

EDITORIAL article Front. Med., 29 May 2024Sec. Precision Medicine Volume 11 - 2024 | https://doi.org/10.3389/fmed.2024.1423460

10.3389/fmed.2024.1423460

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[Risk factors associated with lethality on patients with central cord syndrome].

PubMed (2023)

Patricio Dabdoub-González Edgar Abel Márquez-García Juan Gerardo Reyes-García Jorge Cabrera David Fernando Servín-Carmona

Central Cord Syndrome is the most common incomplete spinal cord injury, and it represents 9% of all spinal injuries of the adult.to determine the risk factors associated with lethality or/and mechanical ventilation (MV) in patients with Central Cord Syndrome (CCS).upon a retrospective cohort with patients with posttraumatic CCS we evaluated at the time of emergency admission and until the hospital discharge. The dependent variable was dead or MV. We calculated incidence, relative risk (RR) with CI95% and a multivariate model for the association of statistically significant variables by means of a risk coefficient model upon the variables that evidenciated tendencies towards risk.From 101 patients with CCS, 85.1% with a severe medullary canal stenosis and 9.9% required MV; the mortality was 13.9%. The only risk factor associated with dead was the use of MV with an RR of 3.6 (CI95% 1.4-9.5); the risk with tendencies towards MV was being older than 60 RR 5.4 (CI95% 0.6-44.2). Other factors demonstrated a tendency towards mortality, but they were not statistically significant.MV is a risk factor associated with mortality, other factors evidenciated tendencies towards mortality; being older than 60, hypertension, diabetes mellitus, narrow spinal canal, more than 20 days of hospital stay and being intervened farther than 10 days from the accident. The incidence of mortality in our sample is greater than thus reported previously on other international articles. To know and identify these and other factors will let us identify patients with a greater risk of complications.el síndrome medular central es la lesión medular incompleta más común y representa el 9% de las lesiones medulares del adulto.determinar la letalidad del síndrome medular central (SMC) y sus factores de riesgo asociados a fallecer y/o uso de ventilación mecánica (VM).cohorte retrospectiva en pacientes con SMC que acuden a urgencias y valorados hasta su egreso. La variable dependiente fue VM o muerte. Se calculó la incidencia, riesgo relativo (RR) e IC95%; se usaron modelos multivariados de asociación con las variables significativas mediante un modelo de cocientes de riesgos, y aquellas que presentaron algún grado de tendencia de acuerdo con el RR por encima de 1.se recolectó la información de una muestra de 101 pacientes con SMC que recibieron atención en la unidad entre 2015 y 2021, 85.1% presentaron estenosis medular, 9.9% de pacientes requirieron VM, la mortalidad fue de 13.9%. El factor de riesgo asociado a muerte fue la VM con RR 3.6 (IC95%: 1.4-9.5); el factor con tendencia a VM fue ser mayor de 60, RR 5.4 (IC95%: 0.6-44.2). Otros factores evidenciaron tendencia a mortalidad o VM sin significancia estadística.el factor de riesgo asociado a mortalidad fue VM, otros evidencian tendencia hacia mortalidad, como ser mayor de 60 años, hipertensión arterial, diabetes mellitus, estenosis medular por debajo de los 10 milímetros, más de 20 días de estancia hospitalaria y ser intervenidos más de 10 días posterior al accidente. La mortalidad en nuestra población se encuentra muy elevada en comparación con estudios internacionales previos. Conocer los factores de riesgo ayudaran a identificar a los pacientes con mayor riesgo de muerte o VM.

10.5281/zenodo.8319828

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Weight Loss at First Month and Development of Tolerance as Possible Predictors of 30 mg Phentermine Efficacy at 6 Months

Journal of Personalized Medicine (2021)

Héctor Isaac Rocha-González Lidia Elizabeth de la Cruz‐Álvarez Ashuin Kammar‐García Samuel Canizales‐Quinteros Juan Carlos Huerta-Cruz

The efficacy of anti-obesity drugs usually does not consider the high degree of interindividual variability in responses to the drug which could affect the decision to withdraw the drug early due to ineffectiveness or to continue therapy according to specific expectations of success. The aim of this study was to analyze body weight loss in kilograms during the first month (1 mo-BWLkg) of treatment with 30 mg phentermine and development of tolerance to phentermine, on its 6-month efficacy. One hundred sixty-six subjects with obesity were individually or jointly analyzed in the study. Subjects with 1 mo-BWLkg of <1 kg, 1-3 kg, 3-5 kg, and ≥5 kg reached 6-month mean percentage body weight reductions (BWR%) of approximately 3%, 5%, 10%, and 15%, respectively. Development of late tolerance (4-6 months) to phentermine had a lower impact than early tolerance (2-3 months). Subjects with 1 mo-BWLkg < 3 kg who developed early tolerance did not achieve relevant BWR% (≥5%) at month 6, while the rest of the subgroups achieved increasing and progressive BWR%, according to their 1 mo-BWLkg range and time of onset of tolerance. The 1 mo-BWLkg and development of tolerance to phentermine could be useful to predict the expected 6-month efficacy trends in obese patients treated with 30 mg phentermine.

Phentermine

Drug tolerance

10.3390/jpm11121354

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Development of a Novel Co-Amorphous Curcumin and L-Arginine (1:2): Structural Characterization, Biological Activity and Pharmacokinetics

Pharmaceutics (2024)

Jose Antonio Mancillas-Quiroz Miriam del Carmen Carrasco‐Portugal Karina Mondragón-Vásquez Juan Carlos Huerta-Cruz Juan Rodrı́guez-Silverio

Background: Curcumin appears to be well tolerated and effective for managing chronic inflammatory pain, but its poor oral bioavailability has been a hurdle in its use as a therapeutic agent. The current study was performed to characterize a novel co-amorphous compound based on curcumin/L-arginine 1:2 (CAC12). Methods: Stability, solubility and structural characterization of the CAC12 were carried out by spectrometry techniques and in vitro assays, whereas the antinociceptive and anti-inflammatory effects were evaluated by CFA or carrageenan models. The mechanism of action was determined by cytokine quantification, and pharmacokinetic parameters were obtained through UPLC-MS/MS. The co-amorphous compound was prepared by fast solvent evaporation. Powder XRD, 13C-NMR, ATR-FTIR and TGA/DSC thermal analysis showed a 1:2 stoichiometry for the CAC12. Results: CAC12 was 1000 times more soluble than curcumin, and it was stable for 1 month at 40 °C and 75% relative humidity or for 60 min in physiological medium at pH 4.5-6.8. Co-amorphous curcumin/L-arginine, but not curcumin + L-arginine, decreased carrageenan- or CFA-induced inflammation and nociception by decreasing IL-1α, IL-1β, IL-6, TNF-α, MCP-1 and CXCL1 cytokines. The bioavailability of free plasmatic curcumin increased about 22.4 times when it was given as CAC12 relative to a phytosome formulation at the equivalent dose. Conclusions: Results suggest the possible use of CAC12 to treat inflammatory pain disorders in human beings.

Characterization

10.3390/pharmaceutics17010011

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GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats

Pharmaceuticals (2022)

Ángel Zúñiga‐Romero Quetzali Rivera-Plata Jesús Arrieta Francisco Javier Flores‐Murrieta Juan Rodrı́guez-Silverio

Orphan G-protein-coupled receptors (GPCR) comprise a large number of receptors which are widely distributed in the nervous system and represent an opportunity to identify new molecular targets in pain medicine. GPR55 and GPR119 are two orphan GPCR receptors whose physiological function is unclear. The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. Mechanical allodynia was evaluated using von Frey filaments. Protein localization and modulation were measured by immunohistochemistry and western blotting, respectively. Intrathecal administration of CID16020046 (selective GPR55 antagonist) or AS1269574 (selective GPR119 agonist) produced a dose-dependent antiallodynic effect, whereas O1062 (GPR55 agonist) and G-protein antagonist peptide dose-dependently prevented the antiallodynic effect of CID16020046 and AS1269574, respectively. Both GPR55 and GPR119 receptors were expressed in spinal cord, dorsal root ganglia and sciatic nerve, but only GPR119 was downregulated after 14 days of spinal nerve ligation. Data suggest that GPR55 and GPR119 participate in the processing of neuropathic pain and could be useful targets to manage neuropathic pain disorders.

Allodynia

10.3390/ph15010067

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Citations (6)