Preetha Abraham

β1-and β2-adrenoceptor induced synaptic facilitation in rat basolateral amygdala

The expression and characteristics of beta-adrenoceptor subtypes (beta1 and beta2) and their agonist actions on synaptic transmission in the basolateral amygdala (BLA) of the rat were examined using in situ hybridization, quantitative real-time PCR, Western blot analysis and field potential recording. In situ hybridization data revealed an intense distribution of beta1-and beta2-adrenoceptor mRNA in the BLA. Real-time PCR analysis of rat amygdala revealed significant transcriptional expression levels of both beta-adrenoceptors, with beta2-adrenoceptors outnumbering beta1-adrenoceptors in a ratio of 2.9 to 1. Bath application of the selective beta1-adrenoceptor agonist xamoterol hemifumarate (10 microM) facilitated the excitatory field synaptic potential evoked in the BLA by stimulation of the external capsule by 186.5+/-10.7% of control amplitude. In the presence of the selective beta1-adrenoceptor antagonist betaxolol hydrochloride (30 microM), the facilitating effects of field excitatory synaptic potential induced by the agonist were reduced to 126.1+/-2.3 % of control amplitude in the BLA. Bath application of the selective beta2-adrenoceptor agonist salmeterol (15 microM) facilitated the excitatory field synaptic potential evoked in the BLA by stimulation of the external capsule by 167.3+/-9.7 % of control amplitude. In the presence of the selective beta2-adrenoceptor antagonist ICI 118,551 HCl (30 microM), the facilitating effects of field excitatory synaptic potential induced by the agonist were reduced to 121.1+/-4.1 % of control amplitude in the BLA. These data suggest that beta-adrenoceptor mediated synaptic facilitation in the amygdala is mediated by both beta1 and beta2-adrenoceptor activation.

Heat exposure induces tissue stress in heat-intolerant, but not heat-tolerant, mice

We investigated the association of systemic and local tissue stress responses with heat–tolerant (TOL) levels in mice. Thirty-eight mice were assigned into control and three heat exposure groups—TOL, moderately tolerant, and intolerant (INT), based on their overall thermal responses. Real-time core temperature, blood pressure, and heart rate (HR) were assessed during heat exposure (39.5°C) under conscious condition. Tissue samples were collected 18–22 h following heat exposure. INT mice had significantly higher peak mean arterial pressure and HR than TOL mice during heat exposure. Plasma corticosterone levels were significantly higher in INT than in control mice. No significant changes in plasma cytokines or markers of oxidative status were observed. INT mice showed significant increases in HSP72 and HSP90 protein and mRNA levels in liver, heart, and gastrocnemius muscles compared to TOL and control mice. In contrast, INT mice had significantly lower heat shock factor 1 and glucocorticoid receptor protein and mRNA levels in these tissues than TOL and control mice. These results indicate that acute heat exposure induces stress responses in various tissues of INT mice, but not TOL mice. Upregulation of stress proteins by acute heat exposure involves both transcriptional and translational pathways.

Single-dose oral quercetin improves redox status but does not affect heat shock response in mice

Inflammation and oxidative stress are considered as likely contributors to heat injury. However, their roles in regulating the heat shock response in vivo remain unclear. We tested the hypothesis that acute quercetin treatment would improve redox status and reduce heat shock responses in mice. Mice underwent two heat tests before and after single oral administration of either quercetin (15 mg/kg) or vehicle. We measured physiologic and biochemical responses in mice during and 18 to 22 hours after heat tests, respectively. There were no significant differences in core temperature, heart rate, or blood pressure between quercetin and vehicle groups during heat exposure. Mice with relatively severe hyperthermia during the pretreatment heat test showed a significant trend toward a lower peak core temperature during the heat test after quercetin treatment. Compared with mice not exposed to heat, quercetin-treated mice had significantly lower interleukin 6 (P < .01) and higher superoxide dismutase levels (P < .01), whereas vehicle-treated mice had significantly lower total glutathione and higher 8-isoprostane levels in the circulation after heat exposure. Heat exposure significantly elevated heat shock proteins (HSPs) 72 and 90 and heat shock factor 1 levels in mouse liver, heart, and skeletal muscles, but no significant differences in tissue HSPs and heat shock factor 1 were found between quercetin- and vehicle-treated mice. These results suggest that a single moderate dose of quercetin is sufficient to alter redox status but not heat stress response in mice. Acute adaptations of peripheral tissues to heat stress may not be mediated by systemic inflammatory and redox state in vivo.

Obesity and African Americans: Physiologic and Behavioral Pathways

Although progress has been made to understand the association between physiological and lifestyle behaviors with regard to obesity, ethnic differences in markers of obesity and pathways towards obesity remain somewhat unexplained. However, obesity remains a serious growing concern. This paper highlights ethnic differences in African Americans and Caucasians that may contribute to the higher prevalence of obesity among African Americans. Understanding ethnic differences in metabolic syndrome criteria, functioning of the hypothalamic pituitary adrenal axis, variations in glucocorticoid sensitivity and insulin resistance, and physical activity and cardiovascular fitness levels may help to inform practical clinical and public health interventions and reduce obesity disparities.

Relationship between Depressive Symptoms and Cardiovascular Disease Risk Factors in African American Individuals

Objective. To examine the relationship between depressive symptoms and cardiovascular disease (CVD) risk factors in a group of African American individuals. Design. A nonrandom sample of 253 (age 43.7 ± 11.6 years; 37% male) African American individuals was recruited by advertisements. Data were obtained by validated questionnaires, anthropometric, blood pressure, and blood sample measurements. Results. Regression analyses were performed to assess the relationship between depressive symptoms and CVD risk factors controlling for socioeconomic status indicators. These analyses demonstrated that those with higher levels of depressive symptoms had larger waist-to-hip ratios, higher percent body fat, higher triglycerides, and were more likely to be smokers. Conclusions. It has been well documented that higher levels of depressive symptoms are associated with higher CVD risk. However, this evidence is derived primarily from samples of predominantly Caucasian individuals. The present investigation demonstrates that depressive symptoms are related to CVD risk factors in African American individuals.

Role of plasma adiponectin /C-reactive protein ratio in obesity and type 2 diabetes among African Americans

BACKGROUND Obesity is a modifiable risk factor for hypertension and T2D. Objective(s): We examined relations between fasting plasma adiponectin (ADIP), C-reactive protein (CRP) concentrations and markers of T2D in African Americans (AA). METHODS Fasting plasma ADIP, CRP, Insulin (IN), HOMA-IR, lipid profiles, body fat percent (%BF), waist circumference (WC), body mass index (BMI) and blood pressure measures were determined in AA women (W: n=77) and men (M: n=34). Participants were classified into: 1) Normal fasting glucose (FG) and Normal %BF; 2) Normal FG and High %BF; and 3) High FG. RESULTS Compared to men, women had significantly higher mean ADIP (W: 31.4±2.9 vs. M: 18.0±4.4 ng/L), CRP (W: 3.2±0.3 vs. M: 2.0±0.5 mg/L), %BF (W: 41.2±0.9 vs. M: 27.2±1.3), and BMI (W: 32.3±0.7 vs. M: 29.2±1.1 kg/m2). Women with normal FG and %BF had significantly higher ADIP (64.0±6.0) and lower CRP (1.3±0.6) concentrations than normal FG/ high %BF (ADIP: 37.0±5.0 and CRP: 3.1 ±0.5) and high FG (ADIP: 15.1±4.1 and CRP: 4.0 ± 0.5) groups. Women with high ADIP to CRP ratio had favorable metabolic and anthropometric profiles. CONCLUSION Low ADIP and high CRP are associated with excessive %BF and FG in AA women. ADIP/CRP, may be useful for detecting metabolic dysregulation.

Quercetin and heat shock response

Dr Chirumbolo commented on the lack of inhibitory effect of quercetin on heat stress response shown in our study [1]. We concluded that a single moderate dose of quercetin is sufficient to alter redox status but not heat stress response in mice. The effects of quercetin were observed as a result of its single-dose application. The findings do not suggest that quercetin itself should not affect the body’s ability to respond to heat-generated stressors, especially at other dosage levels and application procedures. The pharmacokinetics of quercetin after oral administration to rodents have been reported previously [2]. Plasma levels of quercetin were expected to be very low at the time of sample collection and, thus, were not addressed in our study. The orally administered quercetin likely reached effective concentrations during heat stress, as evidenced by alterations in systemic redox homeostasis of quercetin-treated mice. Thus, our results support our conclusion. We agree with Dr Chirumbolo that it would be very interesting to assess heat stress or quercetin effectiveness using plasma T-reg–derived cytokines. In addition, we know that the form of quercetin is very important to the observed responses in that the dihydrated form—dihydroquercetin, unlike quercetin alone—does not inhibit the heat shock protein response under cellular stress [3]. Many questions remain with regard to the form, the timing, and the doses of quercetin. (Supported by the Office of Naval Research Grant N0001411MP20025 and Uniformed Services University Intramural Grant R091EH).

The Association of 5-HTTLPR XLL Genotype with Higher Cortisol Levels in African Americans

Genetic variants of the human serotonin transporter (SERT) may contribute to HPA axis dysregulation. SERT has two promoter region polymorphisms (5-HTTLPR: VNTR and SNP: rs25531), which may alter levels of SERT protein and its function. Combining these polymorphisms creates a functional polymorphism (FN) which may modulate mRNA expression. This study examines the relationship between these genetic variants and morning and evening salivary samples of both cortisol and dehydroepiandrosterone sulfate (DHEAS) concentrations in 269 African American (AA) adults. Resultant allele frequencies for the VNTR, SNP, and FN genotypes were 70% L (2% XLL), 84% A, and 54% LA (2% XLLA), respectively. The XLL genotype was associated with significantly higher concentrations of cortisol (~3X) and DHEAS (~2X) for both VNTR and FN polymorphisms. No significant differences were found for SNP genotypes. Conclusions were that persons with VNTR and FN XLL polymorphisms had significantly higher cortisol and DHEAS concentrations than other genotypes. AAs also appear to have a higher frequency of the rare XL allele than Caucasians. Whether the XLL genotype predisposes AAs to greater health challenges will require further research to determine the implications of these findings.

Army Combat Medic Resilience: The Process of Forging Loyalty

This study presents a grounded theory analysis of in-depth interviews of United States Army Combat Medics (CMs) who had served in Iraq and/or Afghanistan. The study explores how 17 CMs nominated by their peers as resilient cope with military stressors in order to identify the factors that enable them to thrive amidst harsh conditions. Four distinct categories of characteristics unique to this group emerged: (1) social bonding, (2) readiness, (3) dual loyalty as performance, and (4) leader by example. Forging loyalty underpins these characteristics and represents the main process used by resilient CMs and comprised three behavior patterns: (1) commitment to the family, (2) commitment to the military mission, and (3) commitment to their guiding religious and spiritual beliefs. Prominent behavioral tendencies of forging loyalty likely developed during childhood and re-enforced by families, friends, and other role models. Based on the findings, new training and education efforts should focus on developing positive emotional, environmental, and social resources to enhance the health and well-being of service members and their families.

Narrative approach in understanding the drivers for resilience of military combat medics

Introduction Qualitative insights may demonstrate how combat medics (CM) deal with stressors and identify how resilience can potentially develop. Yet, qualitative research is scant in comparison to the many quantitative studies of health outcomes associated with military service. Method Semistructured qualitative interviews were used to collect personal narratives of US Army CMs who had previously served in Iraq or Afghanistan. Results Thematic analysis revealed three key driving forces for how resilience develops in the context of combat and war. The first was patriotism, which captures loyalty and full commitment to the military and its missions. The second was commitment to their family, reflecting the balance of responsibility to family of origin with the obligation one feels towards their military family. The last driving force was faith, or the drive to reach towards the transcendent to provide a moral compass and develop empathy in the face of difficult situations. Conclusions An individual’s commitment to country, military family and faith strengthens their resilience, and this can be used to inform future research efforts as well as current clinical practice.