Background and Aims Chromium and cysteine supplementation have been shown to improve glucose metabolism in animal studies. This study examined the hypothesis that chromium dinicocysteinate (CDNC), a complex of chromium and L-cysteine, is beneficial in lowering oxidative stress, vascular inflammation and glycemia in type 2 diabetic patients. Methods Type 2 diabetic patients enrolled in this study were given placebo for one month for stabilization and then randomized into one of three groups: placebo (P), chromium picolinate (CP) or CDNC, after which they received daily oral supplementation for 3 months. Of the 100 patients enrolled in the study, 74 patients completed it. There were 25 patients in the P supplemented group, 25 in the CP supplemented and 24 in the CDNC supplemented group who completed the study. Blood markers of glycemia, vascular inflammation, HOMA insulin resistance and oxidative stress were determined at randomization and after 3 months of supplementation with P, CP or CDNC. Results There was a significant decrease at 3 months in insulin resistance (p=0.02) and in the levels of protein oxidation (p=0.02) and TNF-α (p=0.01) in the CDNC supplemented cohort compared to baseline. However, there was no statistically significant change in these markers in the CP supplemented group compared to baseline. Insulin levels significantly decreased(p=0.01) for subjects receiving CDNC but not CP. There was no significant impact of supplementation on HbA1c or glucose levels in either of the groups. Conclusions CDNC supplementation lowers insulin resistance by reducing blood levels of TNF-α, insulin, and oxidative stress in type 2 diabetic patients. Therefore, CDNC supplementation has potential as an adjunct therapy for individuals with type 2 diabetes.

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Radiotherapy of intrathoracic and chest wall tumors may lead to exposure of the heart to ionizing radiation, resulting in radiation-induced heart diseases (RIHD). The main manifestations of RIHD become apparent many years after treatment and include cardiomyopathy and accelerated atherosclerosis. This study examines the role of the kallikrein-kinin system (KKS) in RIHD by investigating the cardiac radiation response in a kininogen-deficient Brown Norway Katholiek (BN/Ka) rat model. BN/Ka rats and wild-type Brown Norway (BN) rats were exposed to local heart irradiation with a single dose of 18 Gy or 24 Gy and were observed for 3-6 months. Examinations included in vivo and ex vivo cardiac function, histopathology, gene and protein expression measurements, and mitochondrial swelling assays. Upon local heart irradiation, changes in in vivo cardiac function were significantly less in BN/Ka rats. For instance, a single dose of 24 Gy caused a 35% increase in fractional shortening in BN rats compared to a 16% increase in BN/Ka rats. BN rats, but not BN/Ka rats, showed a 56% reduction in cardiac numbers of CD2-positive cells, and a 57% increase in CD68-positive cells, together with a 52% increase in phosphorylation of Erk1/2. Local heart irradiation had similar effects on histopathology, mitochondrial changes, and left ventricular mRNA levels of NADPH oxidases in the two genotypes. These results suggest that the KKS plays a role in the effects of radiation on cardiac function and recruitment of inflammatory cells. The KKS may have these effects at least in part by altering Erk1/2 signaling.

African Americans (AA) have a higher incidence of cardiovascular disease and vitamin D (VD) deficiency compared with Caucasians. Hydrogen sulfide (H(2)S) is an important signaling molecule. This study examined the hypothesis that blood levels of H(2)S are lower in AA type 2 diabetic patients (T2D). Fasting blood was obtained from T2D and healthy controls. Results showed a significant decrease in plasma levels of cyclic adenosine monophosphate (cAMP) and H(2)S in AA T2D but not in Caucasian T2D when compared with those of respective age- and race-matched healthy controls. Plasma VD levels were significantly lower in AA T2D compared with Caucasian T2D. Cell culture studies demonstrate that 1,25(OH)(2)-VD supplementation significantly increased expression of cystathionine-γ-lyase (CSE), H(2)S formation, and cAMP secretion, but decreased reactive oxygen species in high glucose-treated U937 monocytes. This suggests that VD supplementation upregulates CSE and H(2)S formation and decreases oxidative stress, and that VD deficiency may contribute to the malfunctioning of H(2)S signaling and thus a higher incidence of vascular inflammation in AA. These results lead to the hypothesis that VD supplementation can replenish blood concentrations of H(2)S and cAMP and lower oxidative stress and cardiovascular disease in AA T2D.

Introduction: Sleep deficits associated with sleep apnea and insomnia increase the risk of vascular inflammation and insulin resistance. This study examined the hypothesis that inflammation markers are higher in those diabetic patients who experience sleep deficits compared with those without any history of a sleep disorder. Methods: Fasting blood was obtained after written informed consent, and sleep disorder histories were obtained from type 2 diabetic patients (n = 81) attending clinics of the Louisiana State University Health Sciences Center.Results: There was a significant correlation between body weight and leptin, and leptin in turn was significantly correlated with 10-kDa interferon-g-induced protein (IP-10) levels and insulin resistance in type 2 diabetic patients. Fasting blood levels of leptin, IP-10, and insulin resistance were significantly elevated in patients with sleep deficits compared with diabetics with normal sleep patterns. There were no differences in glycosylated hemoglobin (HbA1c) or fasting glucose in patients with sleep deficits compared with those with normal sleep patterns. Sleep deficits increase circulating levels of leptin, IP-10, and insulin resistance compared to levels seen in patients with diabetes who reported no difficulty with sleep. Patients with sleep apnea had significantly lower hydrogen sulfide (H 2 S) levels compared with patients with normal sleep patterns or patients with insomnia. Low levels of circulating H 2 S could contribute to higher vascular inflammation in patients with sleep apnea. Conclusions: These results suggest that sleep apnea is associated with a decrease in circulating H 2 S and sleep disorders increase the risk of inflammation and insulin resistance, which can contribute to the increased risk of vascular disease in subjects with type 2 diabetes.

Hydrogen sulfide (H2S) is an important signaling molecule whose blood levels have been shown to be lower in certain disease states. Increasing evidence indicates that H2S plays a potentially significant role in many biological processes and that malfunctioning of H2S homeostasis may contribute to the pathogenesis of vascular inflammation and atherosclerosis. This study examined the fasting blood levels of H2S, HDL-cholesterol, LDL-cholesterol, triglycerides, adiponectin, resistin, and potassium in 36 healthy adult volunteers. There was a significant positive correlation between blood levels of H2S and HDL-cholesterol (r=0.49, p=0.003), adiponectin (r=0.36, p=0.04), and potassium (r=0.34, p=0.047), as well as a significant negative correlation with LDL/HDL levels (r= -0.39, p=0.02). This is the first demonstration of an association of circulating levels of H2S with the HDL, LDL, and adiponectin homeostasis in the blood of healthy humans.

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Background and aims Infection with high‐risk (HR) genotypes of the human papillomavirus (HPV) is necessary for and causative of almost all cervical cancers and their precursor condition, cervical intraepithelial neoplasia. These conditions have been sharply reduced by cervical cytology screening, and a further decrease is expected because of the recent introduction of prophylactic HPV vaccinations. While significant attention has been given to gynecologic HPV disease, men can be affected by HPV‐related cancers of the anus, penis, and oropharynx. This literature review aims to address disparities in HPV‐related disease in men, and certain HR male subpopulations, compared with women. Discussion Overall, immunocompetent men are far less likely than women to develop anogenital HPV‐related cancers, despite harboring HR HPV infections at anogenital sites. On the other hand, men who have sex with men and men living with human immunodeficiency virus infection are at considerably higher risk of HPV‐related disease. Historic rates of prophylactic HPV vaccination in males have trailed those of females due to numerous multilevel factors, although, in recent years, this sex gap in vaccination coverage has been closing. In the absence of routine HPV screening in males, therapeutic vaccinations have emerged as a potential treatment modality for preinvasive neoplasia and are in various phases of clinical testing. Conclusion Successful reductions in HPV disease morbidity at the population level must acknowledge and target HPV infections in men.