Pathogenesis of Human Papillomavirus – Immunological Responses to HPV Infection

Papillomavirus is an oncogenic virus which infects mucosal and cutaneous epithelia where it induces benign hyperproliferative lesions. Few studies have been conducted on the causative factors associated with the development of cancer. Infections by high-risk human papillomaviruses (HPVs) have been implicated as causative agents in a variety of cancers such as anogenital, and head and neck cancers. HPVs appear to have evolved mechanisms resulting in escape from host immune surveillance and delay of resolution of infection. The HPV E5 oncoprotein is one of the possible effectors that allows the virus to escape from host immune system through the downregulation of surface classical major histocompatibility complex class I (MHC I) and not the nonclassical MHC I. Lack of classical MHC I in infected cells expressing E5 would allow evasion of cytotoxic T lymphocytes (CTLs) killing and thus establishment and persistence of viral infection

High performance liquid chromatography coupled to electrospray ionisation mass spectrometry method for the detection of salivary human neutrophil alpha defensins HNP1, HNP2, HNP3 and HNP4

Human neutrophil alpha defensins are antimicrobial peptides involved in the first line of defence against invading pathogens. To develop a deeper understanding of the immune responses in relation to airway inflammation and exercise induced epithelial damage it is necessary to have a sensitive method that can detect these peptides in a saliva matrix. A selective and sensitive Liquid Chromatography Mass Spectrometry (LC-MS) method for the detection of four salivary HNP (HNP1, HNP2, HNP3 and HNP4) peptides has been developed and validated. The LC-MS responses of HNPs 1-3 were compared with the response obtained from the traditionally used enzyme-linked immunosorbent assay (ELISA) that measures the combined levels of these three defensins. The peptides were separated on a Phenomenex Kinetex® C8 column (50 x 3.0 mm, 2.6 µm) on an Agilent 1200 series HPLC system using a linear MeOH: H2O: acetic acid (0.1% v/v) gradient. The HPLC was coupled to a Waters Synapt G1 Electrospray Quadrupole Time of Flight mass spectrometer. A full scan range from 100-2000 m/z in the positive ion mode was used for the acquisition. The LC-MS method was linear for concentrations of HNP2 between 0.05 and 1 ng/µL with a LOD of 0.05 ng/µL and LOQ of 0.1 ng/µL. Inter- and intra- assay precisions (%CV) were 0.3 and 14.95%, respectively. HNPs were extracted from saliva by solid-phase extraction (SPE) with a recovery of 80-91%. The cross-validation data revealed no significance quantitative difference between LC-MS and ELISA (R2= 0.96) and confirms that the developed LC-MS method is a reliable method for the detection of these antimicrobial markers. However, superior selectivity in the developed LC-MS method provides a unique opportunity to assess individual alpha defensin levels in the same assay. HNP1, HNP2, HNP3 and HNP4 were evaluated in young athletes before, and up to, 2.5 h after an exercise intervention in order to assess if the developed LC-MS method was sensitive enough to detect rapid changes in their relative levels

Acute effects of a multinutrient supplement on performance, rate of perceived exertion and markers of catabolism in young resistance trainers practitioners

The ingestion of a multi-nutrient containing proteins, carbohydrate and creatine has been shown to enhance acute and chronic responses to resistance training, attenuating fatigue and markers of catabolism training after resistance training workouts. The purpose of this study was to investigate the acute effects of a commercially available multinutrient supplement on neuromuscular fatigue, performance, perception of effort and salivary markers of catabolism, during a bout of resistance circuit training session

A multi-ingredient containing, proteins, carbohydrate and creatine does not attenuate humoral immune response or performance decrease compared to carbohydrate during resistance training

Background: Nowadays, only carbohydrate has shown to be an effective countermeasure to exercise-induced immune dysfunction while the effect of protein remains controversial. The purpose of this study was to investigate the acute effects of a commercially available multi-nutrient supplement on performance and salivary markers of humoral immunity, following a bout of circuit resistance training in young athletes. Methods: Twelve recreationally resistance-trained males (age: 22 ± 1.4 years; body mass 79 ±9.78 kg; 1.81 ± 0.07 m height) volunteered to participate in the study completing 2 randomised controlled circuit resistance training sessions (CT). Participants ingested 2 doses of 500ml of water mixed 60g of a multi-ingredient (MTN) containing whey proteins, carbohydrate, creatine, HMB and sodium bicarbonate or maltodextrin (PL). Beverages were consumed (3 doses of ~166ml) during and after the workout (1 × 500ml). Both MTN and PL looks the same colour and flavour and provide a similar amount of calories (~230 per serving). CT involved three rounds of 7 resistance exercises (CMJs, Bench Press, Parallel-Squat, Upright row, Alternate Lunges, Dead Lift, Push-press, Abdominals) followed by 1 min rest. Participants performed 12 repetitions at 70% 1RM in each of the exercises with no rest in between (only the time to change from one exercise to the next). Measurements included pre and post (30 min and 60 min) salivary markers of humoral immune response: Antimicrobial Peptide, Alpha Defensins (HNP 1-3). The total kg lifted per exercise and in the overall workout was considered as indicator of performance. ANOVA design and Cohen d effect sizes (ES) were used to analyse potential differences between times and treatment conditions. Results: No significant differences were observed between the total weight (kg) lifted per exercise or for the entire session (p > 0.05). HNP 1-3 showed a strong trend (p = 0.06) with a moderate effect size (d = 0.53) at 30 min for the CHO condition [2.001 (1.95) vs 3.037 (2.49) ng/mL], nevertheless, no significant differences were observed at 60 min with respect to the values measured at both pre [3.825 (3.21) vs 2.001 (1.95) ng/mL] and 30 min [3.825 (3.21) vs 3.037 (2.49) ng/mL]. On the other side, HNP 1-3 did not increase at either 30 min [2.464 (3.31) vs 3.656 (3.22) ng/mL] or 60 min [2.464(3.31) vs 2.387 (2.46) ng/mL] post workout for the MTN treatment condition. No differences were observed between the two tested treatment conditions for the three analysed times points (pre, post 30 min and post 60 min). Conclusion: Ingesting both MTN and CHO supplements during and after a circuit resistance-training workout, resulted in no impact on performance. However, even when both nutritional interventions were effective to attenuate the increase of antimicrobial peptide alpha-defensins, MTN showed a stronger effect to blunt exercise-induced immune-dysfunction. These results did not support the notion that only carbohydrate with no added proteins is the only effective nutritional countermeasure against the transient post exercise immunosuppression

Effects of protein vs. carbohydrate supplementation on markers of immune response in master triathletes: A randomized controlled trial

Objective: This study examines the long-term effects of ingesting hydrolyzed beef protein versus carbohydrate on indirect markers of immunity during 10 weeks of endurance training in master-aged triathletes (n = 16, age 35–60 years). Methods: Participants were randomly assigned to either a hydrolyzed beef protein (PRO, n = 8) or nonprotein isoenergetic carbohydrate (CHO, n = 8) condition, which consisted of ingesting 20 g of each supplement, mixed with water, once a day immediately post workout, or before breakfast on nontraining days. Salivary human neutrophil peptides (HNP1–3) were measured before and after performing an incremental endurance test to volitional exhaustion at both pre and post intervention. Additionally, baseline levels of platelets, neutrophils, eosinophil basophils, monocytes, and lymphocytes were determined at pre and post intervention. Results: No significant changes in baseline concentration and secretion rate of salivary HNP1–3 were observed for either treatment. The CHO group showed a nonsignificant decrease in resting HNP1–3 concentrations following the intervention (p = 0.052, effect size d = 0.53). Protein supplementation demonstrated a significant reduction in lymphocyte counts pre to post intervention (mean [SD]: 2.30 [0.57] vs. 1.93 [0.45] 103/mm3, p = 0.046, d = 0.77), along with a moderate but not statistically significant increase (d = 0.75, p = 0.051) of the neutrophil-to-lymphocyte ratio. Conclusions: In master-aged triathletes, postworkout ingestion of only protein, with no carbohydrate, may not be as effective as carbohydrate alone to attenuate negative long-term changes of some salivary and cellular immunological markers. Future studies should consider the co-ingestion of both macronutrients

Effects of supplementation with beef or whey protein versus carbohydrate in master triathletes

Objective: The present study compares the effect of ingesting hydrolyzed beef protein, whey protein, and carbohydrate on performance, body composition (via plethysmography), muscular thickness, and blood indices of health, including ferritin concentrations, following a 10-week intervention program. Methods: After being randomly assigned to one of the following groups: Beef, Whey, or Carbohydrate, twenty four master-age male triathletes (n=8 per treatment) ingested 20 g of supplement, mixed with plain water once a day (immediately after training or before breakfast). All measurements were performed pre and post interventions. Results: Only Beef significantly reduced body mass (p=0.021) along with a trend to preserve or increase thigh muscle mass (34.1±6.1 vs 35.5± 7.4 mm). Both Whey (38.4±3.8 vs 36.9±2.8 mm) and Carbohydrate (36.0±4.8 vs 34.1±4.4 mm) interventions demonstrated a significantly (p<0.05) decreased vastus medialis thickness. Additionally, the Beef condition produced a significant (p<0.05) increase in ferritin concentrations (117±78.3 vs 150.5±82.8 ng/mL). No such changes were observed for the Whey (149.1±92.1 vs 138.5±77.7 ng/mL) and Carbohydrate (149.0±41.3 vs 150.0±48.1 ng/mL) groups. Furthermore, ferritin changes in the Beef group were higher than the modification observed in Whey (p<0.001) and Carbohydrate (p=0.025). No differences were found between Whey and Carbohydrate conditions (p=0.223). No further changes were observed. Conclusion: Ingesting a hydrolyzed beef protein beverage after workout or before breakfast (non training days) can be effective in preserving thigh muscle mass and in improving iron status in male master-age triathletes

Effects of supplementation with beef or whey protein versus carbohydrate in master triathletes

Objective: The present study compares the effect of ingesting hydrolyzed beef protein, whey protein, and carbohydrate on performance, body composition (via plethysmography), muscular thickness, and blood indices of health, including ferritin concentrations, following a 10-week intervention program. Methods: After being randomly assigned to one of the following groups: Beef, Whey, or Carbohydrate, twenty four master-age male triathletes (n=8 per treatment) ingested 20 g of supplement, mixed with plain water once a day (immediately after training or before breakfast). All measurements were performed pre and post interventions. Results: Only Beef significantly reduced body mass (p=0.021) along with a trend to preserve or increase thigh muscle mass (34.1±6.1 vs 35.5± 7.4 mm). Both Whey (38.4±3.8 vs 36.9±2.8 mm) and Carbohydrate (36.0±4.8 vs 34.1±4.4 mm) interventions demonstrated a significantly (p<0.05) decreased vastus medialis thickness. Additionally, the Beef condition produced a significant (p<0.05) increase in ferritin concentrations (117±78.3 vs 150.5±82.8 ng/mL). No such changes were observed for the Whey (149.1±92.1 vs 138.5±77.7 ng/mL) and Carbohydrate (149.0±41.3 vs 150.0±48.1 ng/mL) groups. Furthermore, ferritin changes in the Beef group were higher than the modification observed in Whey (p<0.001) and Carbohydrate (p=0.025). No differences were found between Whey and Carbohydrate conditions (p=0.223). No further changes were observed. Conclusion: Ingesting a hydrolyzed beef protein beverage after workout or before breakfast (non training days) can be effective in preserving thigh muscle mass and in improving iron status in male master-age triathletes

Association of measures of body fat with serum alpha-tocopherol and its metabolites in middle-aged individuals

BACKGROUND AND AIMS: The accumulation of fat increases the formation of lipid peroxides, which are partly scavenged by alpha-tocopherol (α-TOH). Here, we aimed to investigate the associations between different measures of (abdominal) fat and levels of urinary α-TOH metabolites in middle-aged individuals. METHODS AND RESULTS: In this cross-sectional analysis in the Netherlands Epidemiology of Obesity study (N = 511, 53% women; mean [SD] age of 55 [6.1] years), serum α-TOH and α-TOH metabolites from 24-h urine were measured as alpha-tocopheronolactone hydroquinone (α-TLHQ, oxidized) and alpha-carboxymethyl-hydroxychroman (α-CEHC, enzymatically converted) using liquid-chromatography-tandem mass spectrometry. Body mass index and total body fat were measured, and abdominal subcutaneous and visceral adipose tissue (aSAT and VAT) were assessed using magnetic resonance imaging. Using multivariable-adjusted linear regression analyses, we analysed the associations of BMI, TBF, aSAT and VAT with levels of urinary α-TOH metabolites, adjusted for confounders. We observed no evidence for associations between body fat measures and serum α-TOH. Higher BMI and TBF were associated with lower urinary levels of TLHQ (0.95 [95%CI: 0.90, 1.00] and 0.94 [0.88, 1.01] times per SD, respectively) and with lower TLHQ relative to CEHC (0.93 [0.90, 0.98] and 0.93 [0.87, 0.98] times per SD, respectively). We observed similar associations for VAT (TLHQ: 0.94 [0.89, 0.99] times per SD), but not for aSAT. CONCLUSIONS: Opposite to our research hypothesis, higher abdominal adiposity was moderately associated with lower levels of oxidized α-TOH metabolites, which might reflect lower vitamin E antioxidative activity in individuals with higher abdominal fat instead

Prevalence and type distribution of high-risk Human Papillomavirus (HPV) in breast cancer : a Qatar based study

Human papillomavirus (HPV) has been implicated in the etiology of a variety of human cancers. Studies investigating the presence of high-risk (HR) HPV in breast tissue have generated considerable controversy over its role as a potential risk factor for breast cancer (BC). This is the first investigation reporting the prevalence and type distribution of high-risk HPV infection in breast tissue in the population of Qatar. A prospective comparison blind research study herein reconnoitered the presence of twelve HR-HPV types’ DNA using multiplex PCR by screening a total of 150 fresh breast tissue specimens. Data obtained shows that HR-HPV types were found in 10% of subjects with breast cancer; of which the presence of HPV was confirmed in 4/33 (12.12%) of invasive carcinomas. These findings, the first reported from the population of Qatar, suggest that the selective presence of HPV in breast tissue is likely to be a related factor in the progression of certain cases of breast cancer

Effects of protein–carbohydrate supplementation on immunity and resistance training outcomes: a double-blind, randomized, controlled clinical trial

Purpose: To examine the impact of ingesting hydrolyzed beef protein, whey protein, and carbohydrate on resistance training outcomes, body composition, muscle thickness, blood indices of health and salivary human neutrophil peptides (HNP1-3), as reference of humoral immunity followed an 8-week resistance training program in college athletes. Methods: Twenty-seven recreationally physically active males and females (n = 9 per treatment) were randomly assigned to one of the three groups: hydrolyzed beef protein, whey protein, or non-protein isoenergetic carbohydrate. Treatment consisted of ingesting 20 g of supplement, mixed with orange juice, once a day immediately post-workout or before breakfast on non-training days. Measurements were performed pre- and post-intervention on total load (kg) lifted at the first and last workout, body composition (via plethysmography) vastus medialis thickness (mm) (via ultrasonography), and blood indices of health. Salivary HNP1-3 were determined before and after performing the first and last workout. Results: Salivary concentration and secretion rates of the HNP1-3 decreased in the beef condition only from pre-first-workout (1.90 ± 0.83 μg/mL; 2.95 ± 2.83 μg/min, respectively) to pre-last-workout (0.92 ± 0.63 μg/mL, p = 0.025, d = 1.03; 0.76 ± 0.74 μg/min, p = 0.049, d = 0.95), and post-last-workout (0.95 ± 0.60 μg/mL, p = 0.032, d = 1.00; 0.59 ± 0.52 μg/min, p = 0.027, d = 1.02). No other significant differences between groups were observed. Conclusions: Supplementation with a carbohydrate–protein beverage may support resistance training outcomes in a comparable way as the ingestion of only carbohydrate. Furthermore, the ingestion of 20 g of hydrolyzed beef protein resulted in a decreased level and secretion rates of the HNP1-3 from baseline with no negative effect on blood indices of health