Downregulation of intestinal multidrug resistance transporter 1 in obese mice: Effect on its barrier function and role of TNF-α receptor 1 signaling.

OBJECTIVES: Multidrug resistance transporter 1 (Mdr-1) is a relevant component of the intestinal transcellular barrier that decreases absorption of oral drugs, thus modulating their bioavailability. Obese patients with metabolic disorders take medications that are subjected to intestinal metabolism and the Mdr-1-dependent barrier. This study evaluated the effect of a high-fat diet (HFD; 40% fat for 16 wk) on Mdr-1 expression and transport activity in C57BL/6 (C57) male mice. Comparable studies were performed in tumor necrosis factor α (TNF-α) receptor 1 knockout mice (R1KO) to delineate a possible role of TNF-α signaling. METHODS: mRNA expression was evaluated by real-time polymerase chain reaction and protein levels by western blotting and immunohistochemistry. Mdr-1 activity was assessed using the everted intestinal sac model, with rhodamine 123 as the substrate. Statistical comparisons were made using the Student t test or one-way analysis of variance followed by the post hoc Tukey test. RESULTS: Mdr-1 protein, as well as its corresponding Mdr1a and Mdr1b mRNA, was decreased in C57-HFD mice compared with controls. Immunohistochemical studies confirmed downregulation of Mdr-1 in situ. These results correlated with a 48% decrease in the basolateral to apical transport of rhodamine 123. In contrast, R1KO-HFD modified neither intestinal Mdr-1 mRNA nor its protein expression or activity. In addition, C57-HFD showed elevated intestinal TNF-α mRNA and protein (enzyme-linked immunosorbent assay) levels, whereas R1KO-HFD was undetectable or had a lower increase, respectively. CONCLUSIONS: This study demonstrated an impairment of the Mdr-1 intestinal barrier function induced by HFD as a consequence of downregulation of both Mdr-1 gene homologues, resulting in impaired Mdr-1 protein expression. Inflammatory response mediated by TNF-α receptor 1 signaling was likely involved.

Tratamiento de una lesión primaria por loxoscelismo cutáneo, complicada por infección, con solución electrolizada de superoxidación con pH neutro (SES). Informe de un caso / Treatment of a Primary Lesion of Cutaneous Loxoscelismo, Complicated by Infection, with Neutral Electrolyzed Water (SES). A Case Report

Resumen Las lesiones por loxoscelismo cutáneo pueden complicarse con infecciones concomitantes debido a que el diagnóstico es presuntivo y no existe un esquema de tratamiento específico. Las soluciones electrolizadas de superoxidación de pH neutro (SES) han mostrado ser eficaces en el tratamiento de lesiones cutáneas severas por sus efectos antisépticos y de regeneración del tejido, por lo que podrían ser un método de curación para las lesiones por loxoscelismo cutáneo. Presentamos el caso de un paciente del sexo masculino, de 73 años, cardiópata, diagnosticado con loxoscelismo cutáneo en el tobillo izquierdo que recibió tratamiento convencional de antibióticos, antiinflamatorios, antihistamínicos y analgésicos, y fue dado de alta. Sin embargo, la lesión evolucionó y fue tratada de manera casera con remedios tradicionales; esta se extendió 360° y presentaba exudado fétido al momento en que decidió regresar al hospital. En la clínica de heridas se optó por manejar la lesión en primera instancia con lavados con SES y desbridamiento, seguido de lavados con SES y apósitos de gel SES 3 veces al día, por 3 días, logrando el control de la infección en este tiempo. Posteriormente, con el régimen basado en la aplicación de SES cada 48 horas, se observó la aparición del tejido de granulación al día 7, y la reepitelización en el día 45 de iniciado el abordaje con SES; el cierre total de la lesión se logró el día 67. El esquema de tratamiento basado en el uso de soluciones electrolizadas de superoxidación de pH neutro mostró ser eficaz en el control de la infección y en la inducción del proceso de regeneración del tejido que llevó al cierre de la herida sin complicaciones para el paciente.

Abstract Cutaneous loxoscelism wounds can be complicated by concomitant infections because the diagnosis is presumptive and there is no specific treatment scheme. Neutral electrolyzed water (SES) has been shown to be effective in the treatment of severe skin lesions due to their antiseptic and tissue regeneration effects and could therefore be a healing method for skin loxoscelism lesions. We present the case of a 73-year-old male patient with heart disease, diagnosed with cutaneous loxoscelism in the left ankle, who received conventional treatment of antibiotics, anti-inflammatories, antihistaminics, and analgesics. He was discharged. However, the injury developed and was treated at home with traditional remedies. It extended 360° and presented a fetid exudate at the time he decided to return to the hospital. In the clinic it was decided to manage the lesion in the first instance with washes with SES and debridement, followed by washes with SES and SES gel dressings three times a day for 3 days, achieving control of the infection at that moment. Subsequently, with the regimen based on the application of SES every 48 hours, the appearance of granulation tissue was observed on day 7, and re-epithelialization on day 45 after starting the SES approach, the total closure of the lesion was achieved on day 67. The treatment scheme based on the use of neutral electrolyzed water proved to be effective in controlling the infection and in inducing the tissue-generation process that led to the closure of the wound without complications for the patient.

Nasopharyngeal and oropharyngeal rinses with neutral electrolyzed water prevents COVID-19 in front-line health professionals: A randomized, open-label, controlled trial in a general hospital in Mexico City.

The worldwide efforts that healthcare professionals are making in the COVID-19 pandemic is well known, and the high risk of illness and death that front-line staff experience on a daily basis is a reality, despite well-defined protocols for the use of personal protective equipment. In addition, it is well known that vaccination is still faraway to be achieved worldwide and that new variants are emerging, thus additional protective measures must be explored. A prospective open-label randomized controlled clinical trial was performed on front-line medical staff from the Dr. Enrique Cabrera General Hospital in México City to evaluate the effectiveness of nasopharyngeal and oropharyngeal rinses with a neutral electrolyzed water, known as SES, to reduce the risk of COVID-19 disease among front-line, not vaccinated medical staff. A total of 170 volunteers were enrolled and equally divided in a control group and SES group. All members of the trial wore the adequate personal protection equipment at all times while performing their duties, as required by standard COVID-19 safety protocols. Additionally, the SES group participants followed a prophylactic protocol with SES (oral and nasal rinses, three times a day for 4 weeks). All participants were monitored for COVID-19 symptoms and disease in a time-frame of 4 weeks and the incidence of illness per group was registered. The relative risk of disease, associated with each treatment was calculated. The presence of COVID-19-positive cases, in the group that received the nasal and oral rinses with SES was 1.2%, while in the group that did not do the SES rinses (control group), it was 12.7% (P=0.0039 and RR=0.09405; 95% CI of 0.01231-0.7183). The prophylactic protocol was demonstrated as a protective factor, in more than 90%, for developing the disease, and without adverse effects. Nasal and oral rinses with SES may be an efficient alternative to reinforce the protective measures against COVID-19 disease and should be further investigated. The present clinical trial was retrospectively registered in the Cuban public registry of clinical trials (RPCEC) database (March 16, 2021; PREVECOVID-19: RPCEC00000357).