Variants in genes of innate immunity,appetite control and energy metabolism are associated with host cardiometabolic health and gut microbiota composition

ABSTRACT

Identifying the genetic and non-genetic determinants of obesity and related cardiometabolic dysfunctions is cornerstone for their prevention, treatment, and control. While genetic variants contribute to the cardiometabolic syndrome (CMS), non-genetic factors, such as the gut microbiota, also play key roles. Gut microbiota is intimately associated with CMS and its composition is heritable. However, associations between this microbial community and host genetics are understudied. We contribute filling this gap by genotyping 60 variants in 39 genes of three modules involved in CMS risk, measuring cardiometabolic risk factors, and characterizing gut microbiota in a cohort of 441 Colombians. We hypothesized that CMS risk variants were correlated with detrimental levels of clinical parameters and with the abundance of disease-associated microbes. We found several polymorphisms in genes of innate immunity, appetite control, and energy metabolism that were associated with metabolic dysregulation and microbiota composition; the associations between host genetics and cardiometabolic health were independent of the participants’ gut microbiota, and those between polymorphisms and gut microbes were independent of the CMS risk. Associations were also independent of the host genetic ancestry, diet and lifestyle. Most microbes explaining genetic-microbiota associations belonged to the families Lachnospiraceae and Ruminococcaceae. Multiple CMS risk alleles were correlated with increased abundance of beneficial microbiota, suggesting that the phenotypic outcome of the evaluated variants might depend upon the genetic background of the studied population and its environmental context. Our results provide additional evidence that the gut microbiota is under the host genetic control and present pathways of host–microbe interactions.     

Cold exposure and left ventricular diastolic performance in coronary artery disease

It is known that cold exposure is accompanied by coronary artery vasoconstriction and ischemia in patients with coronary artery disease (CAD). The aim of the present study was to evaluate the response of left ventricular (LV) diastolic and systolic functions, estimated by means of Doppler echocardiography, to cold pressor test (CPT) in patients with CAD. Twenty-five male patients (mean age 50.8 +/- 8.1 years) with documented CAD underwent CPT with Doppler echocardiographic assessment of LV diastolic and systolic functions. According to the development of ischemic response to CPT, all patients were divided into 2 groups: group 1, 10 patients with ischemia and group 2, 15 patients without ischemia during CPT. Cold exposure caused significant increase in blood pressure with no changes in heart rate in all CAD patients. Patients with signs of ischemia during cold exposure had lower transmitral flow velocity during early filling (p < 0.001), prolonged isovolumic relaxation time (p < 0.04), shortened deceleration time of early transmitral flow velocity (p < 0.001), and higher values of Doppler-derived index of myocardial performance (p < 0.0001) than those without ischemic response to CPT. Cold exposure in CAD patients through stimulating of vasoconstriction and ischemia was associated with derangements in LV myocardial performance, manifested by delayed relaxation, impaired stiffness, and reduced contractility.     

P Wave Amplitude and Duration may Predict Immediate Recurrence of Atrial Fibrillation After Internal Cardioversion

Background: Although internal cardioversion (IC) for atrial fibrillation (AF) is effective at restoring sinus rhythm, immediate recurrence (IR) of AF after IC is a major and largely unpredictable clinical problem. The purpose of the study was to determine the role of P wave duration and amplitude in prediction of IR of AF after IC. Forty‐five consecutive patients undergoing IC for chronic AF were evaluated. Material and Methods: After successful IC, 1‐minute ECG recording was obtained in all patients. P wave duration and amplitude in Lead II and V₁ were measured using computer. Forty patients (88%) had successful IC. Thirteen patients experienced IR of AF within 1 minute of restoring sinus rhythm. Results and Conclusion: As a result, the incidence of IR of AF after IC was higher in the patients with shorter P wave amplitude (for lead II P < 0.01 , for V₁P < 0.01 ) and larger P wave duration (for lead II P < 0.01 , for V₁P < 0.05 ).     

The efficiency of granulocyte colony-stimulating factor in hemorrhagic mucositis and febrile neutropenia resulted from methotrexate toxicity

Methotrexate (MTX) remains one of the most frequently used anti-metabolite agents in dermatology. MTX is an analog of folate that competitively and irreversibly inhibits dihydrofolate reductase. Oral mucositis is a common side effect of chemotherapy drugs and is characterized by erythema, pain, poor oral intake, pseudomembranous destruction, open ulceration and hemorrhage of the oral mucosa. In this paper, we report a 32-year-old female with a case of mucositis due to MTX intoxication that resulted from an overdose for rheumatoid arthritis. The patient had abdominal pain, vomiting, and nausea. During follow-up, the patient’s white blood cell count was found to be 0.9?×?10⁹/L (4–10?×?10⁹/L). The patient developed fever exceeding 40?°C. The patient was consulted to the hematology service. They suggested using granulocyte colony-stimulating factor for febrile neutropenia. On the fifth day of treatment, the white blood cell count reached 5.3?×?10⁹/L and the patient’s fever and mucositis started to resolve. Here, we presented a case of hemorrhagic mucositis and febrile neutropenia resulted from high-dose MTX that responded very well to granulocyte colony-stimulating factor treatment and we reviewed the literature.     

An Evaluation of the Protective Effects of Thymoquinone on Amikacin-Induced Ototoxicity in Rats

Objectives

In this study we investigated the probable protective effects of thymoquinone on amikacin-induced ototoxicity in rats.

Methods

Thirty-two healthy rats were divided into four groups (amikacin, amikacin+thymoquinone, thymoquinone, and no treatment). Thymoquinone was fed to the rats via oral gavage in a dose of 40 mg/kg/day throughout the study period of 14 days. Amikacin was given by the intramuscular route in a dose of 600 mg/kg/day. Audiological assessment was conducted by the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) tests, administered to all rats at the beginning of the study, and also on days 7 and 15. Biochemical parameters were calculated at the termination of the study to evaluate the oxidative status.

Results

There were significant decreases in DPOAE values and significant increases in ABR thresholds of the amikacin group on days 7 and 15, as compared to the amikacin+thymoquinone group. While ABR thresholds of the amikacin group increased significantly on days 7 and 15 as compared to their initial values, there were no significant differences between the initial and the 7th and 15th day values of ABR thresholds in the amikacin+thymoquinone group. Total oxidant status and oxidative stress index values of the amikacin+thymoquinone group were significantly lower than those of the amikacin group. Total antioxidant status values of the amikacin+thymoquinone group were significantly higher than those of the amikacin group.

Conclusion

Our study has demonstrated that the ototoxic effect brought forth by amikacin could be overcome with the concurrent use of thymoquinone.