Effects of smoking severity and moderate and severe periodontitis on serum C-reactive protein levels: an age- and gender-matched retrospective cohort study

Abstract

Background and purpose: C-reactive protein (CRP) which might affect cardiovascular events can be affected by chronic diseases and smoking. Since the effects of smoking dosage as well as the mutual effect of smoking and periodontitis on CRP levels have not been evaluated, we aimed to assess these.

Materials and methods: This retrospective age- and gender-matched study was performed on 120 dental patients. Clinical attachment loss, pocket probing depth (PPD), bleeding on probing (BoP), O’Leary plaque index and serum CRP were recorded. Patients were divided into one control and five cohort groups (n?=?20 each) according to smoking severity [pack years (PY) below or above 30] and periodontal condition (healthy periodontium and moderate/severe periodontitis). The effects of clinical measurements, age, gender, smoking and periodontitis on CRP were assessed using one- and two-way analyses of variance, Tukey and Bonferroni post hoc tests, and multiple linear regression (α?=?0.05).

Results: CRP concentrations were 0.07255?±?0.009539, 0.09645?±?0.010625, 0.122235?±?0.018442, 0.3758?±?0.187369, 0.81595?±?0.0410299 and 1.8717?±?0.652728?mg/l, respectively, in the control (PY?≤?30 with healthy periodontium), cohort 1 (PY?>?30 with healthy periodontium), cohort 2 (PY?≤?30 with moderate periodontitis), cohort 3 (PY?>?30 with moderate periodontitis), cohort 4 (PY?≤?30 with severe periodontitis) and cohort 5 (PY?>?30 with severe periodontitis). The positive effects of age, smoking severity, periodontitis and PPD, on CRP increase were significant (Regression p?<?0.02). BoP had a negative effect (p?=?0.015).

Conclusions: Clinicians should warn the patients, especially the older ones, about the effects of their gingival health and smoking on their cardiovascular condition.     

Increases in serum concentration of human heart-type fatty acid-binding protein following elective coronary intervention

Background: Heart-type fatty acid-binding protein (H-FABP) is considered a marker of myocardial necrosis but whether or not it is modified by myocardial ischemia is not clear. We sought to investigate if H-FABP serum levels increase following non-urgent coronary angioplasty.

Methods: We studied 31 patients undergoing coronary angioplasty. Peripheral venous samples were drawn immediately before angioplasty, 1?h after the first balloon inflation and 24?h after the procedure and assayed for H-FABP.

Results: Serum levels of H-FABP increased significantly at 1?h vs baseline from 2554?±?1268 to 3322?±?245?pg?ml^?1 (p?=?0.024). However, no differences were observed between 1?h and 24?h after angioplasty (3268?±?1861 vs 3322?±?2459?pg ml^?1, p?=?0.87). Moreover, no significant difference was observed when we compared 24?h after angioplasty with the baseline (3268?±?1861vs 2554?±?1268?pg ml^?1, p?=?0.112).

Conclusions: We conclude that H-FABP significantly increases after elective coronary angioplasty at 1?h compared with baseline values; whether or not this has any prognostic significance for future events, as it occurs with troponins, needs to be studied further.     

Role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) in assessing disease control in Asian patients with axial spondyloarthritis

Introduction: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) which are used for assessment of axial spondyloarthritis (AxSpA) related disease activity have poor specificity and sensitivity. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) have not been investigated as disease activity markers among Asian AxSpA patients.

Methodology: A retrospective, cross-sectional study was conducted in Singapore General Hospital from January 2013 to December 2015 to investigate the role of NLR, PLR and MPV as disease activity markers in AxSpA patients.

Results: The mean age of patients (n?=?122) was 37.0?±?12.5 years old and majority of them were male (n?=?93, 76.2%). No significant differences were found between patients with disease with regards to age, gender, ethnicity, HLAB-27 status, age at onset of diagnosis of AxSpA, duration of disease and comorbidities such as cardiac disease (p?>?0.05).

There were no significant differences in the ESR, NLR, PLR and MPV between the four disease activity groups (p?>?0.05). However, patients with very high disease activity had higher ESR and CRP compared to patients with inactive disease and moderate disease activity (p?Conclusion: NLR, PLR and MPV were not associated with disease activity in Asian AxSpA patients.     

Prostaglandin Endoperoxide H Synthase-2 (PGHS-2) Variants and Risk of Obesity and Microvascular Dysfunction Among Tunisians: Relevance of rs5277 (306G/C) and rs5275 (8473T/C) Genetic Markers

The purpose of this study was to determine the impact of six PGHS-2 genetic variants on obesity development and microvascular dysfunction. The study included 305 Tunisian subjects (186 normal weights, 35 overweights and 84 obeses). PCR analyses were used for allelic discrimination between polymorphisms. Prostaglandin (PGE2, PGI2), leptin, and matrix metalloproteinase (MMP1, 2, 3, 9) levels were evaluated by ELISA. Fatty acid composition was performed by gas chromatography–mass spectrometry. Our results revealed that subjects carrying the PGHS-2 306CC (rs5277) and 8473CC (rs5275) genotypes present higher anthropometric values compared to wild-type genotypes (306GG, BMI (Kg/m²): 27.11?±?0.58; WC (cm): 93.09?±?1.58; 306CC, BMI: 33.83?±?2.46; WC: 109.93?±?5.41; 8473TT, BMI: 27.75?±?0.68; WC: 93.96?±?1.75; 8473CC, BMI: 33.72?±?2.2; WC: 117.89?±?2.94). A reduced microvascular reactivity and a higher PGE2 level were also found in individuals with the 306CC and 8473CC genotypes in comparison to 306GG and 8473TT carriers (306GG, Peak Ach-CVC (PU/mmHg): 0.46?±?0.03; PGE2 (pg/ml): 7933.1?±?702; 306CC, Peak Ach-CVC: 0.24?±?0.01; PGE2: 13,380.3?±?966.2; 8473TT, Peak Ach-CVC: 0.48?±?0.05; PGE2: 7086.41?±?700.31; 8473CC, Peak Ach-CVC: 0.23?±?0.01; PGE2: 13,175.7?±?1165.8). Fatty acid analysis showed a significant increase of palmitic acid (PA) (34.2?±?2.09 vs. 16.82%?±?1.76, P?<?0.001), stearic acid (SA) (25.76?±?3.29 vs. 9.05%?±?2.53, P?<?0.001), and linoleic acid (LA) (5.25?±?1.18 vs. 0.5%?±?0.09, P?<?0.001) levels in individuals carrying the PGHS-2 306CC genotype when compared to GG genotype individuals. Subjects with the 8473CC genotype showed also a significant increase of PA, SA ,and LA levels when compared to TT genotype carriers (PA: 38.02?±?1.51 vs. 12.65%?±?1.54, P?<?0.001; SA: 32.96?±?1.87 vs. 1.38%?±?0.56, P?<?0.001; LA: 26.84?±?2.09 vs. 3.7%?±?1.54, P?<?0.001). Logistic regression analysis revealed that PGHS-2 306CC and 8473CC variants are significantly associated with obesity status (OR 6.25, CI (1.8–21.6), P?=?0.004; OR 3.01, CI (1.13–8.52), P?=?0.03, respectively). Haplotypes containing the C₃₀₆:T₈₄₇₃ (OR 2.91; P?=?0.01) and G_306:C₈₄₇₃ (OR 5.25; P?=?0.002) combinations were associated with an enhanced risk for obesity development in the studied population. In conclusion, our results highlight that PGHS-2 306G/C and 8473T/C variants could be useful indicators of obesity development, inflammation, and microvascular dysfunction among Tunisians.

     

A comparison of HMGB1 concentrations between cerebrospinal fluid and blood in patients with neurological disease

Aims: To determine whether a correlation exists between paired cerebrospinal fluid (CSF) and serum levels of a novel inflammatory biomarker, high-mobility group box 1 (HMGB1), in different neurological conditions.

Methods: HMGB1 was measured in the serum and CSF of 46 neurological patients (18 idiopathic intracranial hypertension [IIH], 18 neurological infection/inflammation [NII] and 10 Rasmussen’s encephalitis [RE]).

Results: Mean serum (±?SD) HMGB1 levels were 1.43?±?0.54, 25.28?±?27.9 and 1.89?±?1.49?ng/ml for the patients with IIH, NII and RE, respectively. Corresponding mean (±?SD) CSF levels were 0.35?±?0.22, 4.48?±?6.56 and 2.24?±?2.35?ng/ml. Both CSF and serum HMGB1 was elevated in NII. Elevated CSF HMGB1 was demonstrated in RE. There was no direct correlation between CSF and serum levels of HMGB1.

Conclusion: Serum HMGB1 cannot be used as a surrogate measure for CSF levels. CSF HMGB1 was elevated in NII and RE, its role as a prognostic/stratification biomarker needs further study.     

Relationships of Different Blood Pressure Categories to Indices of Inflammation and Platelet Activity in Sustained Hypertensive Patients with Uncontrolled Office Blood Pressure

Failure to decrease blood pressure (BP) normally during nighttime (non-dipping) in hypertension is associated with higher cardiovascular morbidity and mortality. In addition, non-dipping BP is associated with increased platelet activity and inflammatory response; however, there has been no study to evaluate the relationship of non-dipping BP to indices of platelet activity and inflammation in uncontrolled hypertensive patients. In the present study, hypertensive subjects with uncontrolled office BP were firstly divided into three groups: 84 subjects with white coat effect and 365 subjects with true uncontrolled hypertension. Then, true uncontrolled hypertensive patients were divided into two groups: 158 patients with dipping and 207 patients with non-dipping. Mean platelet volume (MPV), uric acid (UA), γ-glutamyltransferase (GGT), C-reactive protein (CRP), and high-sensitivity CRP (hs-CRP) levels were studied. The general characteristics and risk factors for coronary artery disease (CAD) of the study population were similar among the groups. MPV, UA, GGT, CRP, and hs-CRP levels were significantly higher in non-dipper group than both dipper and white coat effect groups, and were significantly higher in dipper group than in white coat effect group (MPV: 9.1?±?1.3, 8.7?±?1.1, and 8.0?±?0.9 fL; UA: 6.9?±?1.2, 5.9?±?1.4, and 4.1?±?0.8?mg/dL; GGT: 38.9?±?11.1, 33.6?±?14.9, and 25.2?±?9.2 U/L; CRP: 7.1?±?2.4, 6.2?±?1.9, and 3.9?±?0.8?mg/dL; hs-CRP: 3.8?±?1.5, 3.3?±?1.2, and 2.0?±?0.6, non-dipper, dipper, and white coat effect groups, respectively, all p values <0.01). All study parameters strongly correlated with each other. In conclusion, in hypertensive patients with uncontrolled office BP, presence of non-dipping BP is associated with increased platelet activity and inflammation, which can be one of the underlying plausible mechanisms of non-dipping BP status.     

Acute and delayed responses of C-reactive protein,malondialdehyde and antioxidant markers after resistance training session in elite weightlifters: Effect of time of day

The aim of this study was to investigate the effect of an Olympic-Weightlifting-session followed by 48-h recovery period on the oxidative and antioxidant parameters’ diurnal variation. Nine weightlifters (21?±?0.5 years) performed, in randomized order, three Olympic-Weightlifting-sessions at 08?h:00, 14?h:00 and 18?h:00. Blood samples were collected: at rest and 3?min and 48?h after each session. C-reactive protein (CRP), rate of lipid peroxidation and antioxidant activities were assessed. At rest, analysis of variance showed a significant time of day (TOD) effect (p?<?0.05) for uric acid, catalase and glutathione peroxidase with higher values at 14?h:00 and 18?h:00 compared with 08?h:00. However, no significant TOD effect for malondialdehyde, total bilirubin and CRP was observed. Given the profound changes (p?<?0.001) in the post-training session values, these diurnal variations have been altered immediately and even 48?h after the training sessions. Despite the significant decreases in the post-training values after the 48-h recovery period (p?<?0.05), levels of lipid peroxidation and enzymatic defense remained elevated (p?<?0.05) 48?h after the morning training session. However, after the afternoon and evening sessions, the same period was sufficient to return values to the baseline levels. In conclusion, the morning session seems to generate the most important acute and delayed lipid peroxidation responses. Therefore, weightlifting coaches should avoid scheduling their training sessions in the morning-hours.     

Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors

Background:?STEALTH^® liposomal CKD-602 (S-CKD602), a camptothecin analog, is eliminated by the reticuloendothelial system (RES), which consists of cells, including monocytes. We evaluated the relationship between monocyte and absolute neutrophil counts (ANCs) in the blood and pharmacokinetic disposition of S-CKD602 and nonliposomal CKD-602 (NL-CKD602) in patients.

Methods:?As part of a phase I study of S-CKD602 and phase I and II studies of NL-CKD602, the percent decreases in ANC and monocytes at their nadir were calculated. After S-CKD602, the amount of CKD-602 recovered in urine was measured.

Results:?For S-CKD602 in patients <60 years, the percent decrease in ANC and monocytes were 43?±?31 and 58?±?26%, respectively (P?=?0.001). For S-CKD602 in patients ≥60, the percent decrease in ANC and monocytes were 41?±?31 and 45?±?36%, respectively (P?=?0.50). For NL-CKD602 (n?=?42), the percent decrease in ANC and monocytes were similar (P?>?0.05). For S-CKD602, the relationship between the percent decrease in monocytes and CKD-602 recovered in urine was stronger in patients <60 (R²?=?0.82), compared with patients ≥60 (R²?=?0.30).

Conclusions:?Monocytes are more sensitive to S-CKD602, compared with neutrophils, and the increased sensitivity is related to the liposomal formulation, not CKD-602. These results suggest that monocytes engulf S-CKD602, which causes the release of CKD-602 from the liposome and toxicity to the monocytes, and that the effects are more prominent in patients <60.     

Life table of Gaeolaelaps aculeifer (Acari: Laelapidae) feeding on larvae of Lycoriella auripila (Diptera: Sciaridae) with stage-specific estimates of consumption

Gaeolaelaps aculeifer (Canestrini, 1883) is a soil-dwelling predatory mite with potential for use as a biological control agent of fungus gnats (Diptera: Sciaridae) in mushroom production. The life table, predation rate and population growth rate of G. aculeifer on a diet of larvae of the sciarid fly, Lycoriella auripila, at 23?±?1°C, 60?±?5% RH and a photoperiod of 0:24 (L:D)?h was investigated. The results revealed that the duration of egg, larva, protonymph, deutonymph, females and males of G. aculeifer were 3.8?±?0.1, 1.4?±?0.1, 3.9?±?0.1, 4.1?±?0.1, 67.7?±?2.8 and 60.3?±?3.1 days, respectively. Net reproductive rate (R₀) was 54.8?±?7.1 offspring, intrinsic rate of increase (r) was 0.12?±?0.01 offspring day^?1, finite rate of increase (λ) was 1.13?±?0.01 day^?1and mean generation time (T) was 32.3?±?0.6 days. The predator consumed a mean of 0.08?±?0.05, 1.73?±?0.18, 3.16?±?0.28 and 75.9?±?7.1 third instar L. auripila larvae during the larval (1.3?±?0.1 days), protonymph (3.9?±?0.1 days), deutonymph (4.1?±?0.1 days) and adult (52.6?±?2.2 days) stages. Population parameters and consumption rates suggest that G. aculeifer has good potential as a biological control agent of L. auripila in mushroom production.     

Postoperative peak serum C-reactive protein is a predictor of outcome following liver transplantation for hepatocellular carcinoma

Context: C-reactive protein (CRP), a biomarker of inflammation, may correlate with prognosis in several malignancies.

Objective: To investigate the prognostic impact of early postoperative peak serum levels of CRP on tumor-specific outcome in 106 liver transplant patients with hepatocellular carcinoma (HCC).

Methods and results: In multivariate Cox regression analysis, a posttransplant elevated peak CRP level (>versus?≤?3.5?mg/dl) was identified as an independent predictor of poor recurrence-free survival (p?=?0.01; HR?=?4.04; CI?=?1.399–11.640).

Conclusion: Early postoperative serum CRP may serve as a useful inflammation-based biomarker of outcome in liver transplant patients with HCC.     

Ischaemia-modified albumin in pulmonary hypertension

Background: Pulmonary hypertension (PH) may be associated with subendocardial ischaemia. We investigated whether ischaemia-modified albumin (IMA), an established marker of ischaemia, is elevated in stable patients with PH.

Methods: We studied 32 patients with PH and an equal number of age-matched normal volunteers. We assessed serum IMA levels with the albumin cobalt-binding test.

Results: Patients’ mean ± SD (range) pulmonary arterial pressure was 56?±?12 (33–73) mmHg and their exercise capacity was 394?±?145 (121–688) m in the 6-min walk test. IMA was 92?±?14 (69–115) U ml^?1 in the patient group and 93?±?9.4 (76–122) U ml^?1 in the control group with no significant difference between the two (p?=?0.85), although almost one-third of the patients had detectable troponin-I.

Conclusions: We conclude that IMA, a marker of ischaemia, does not differ in patients with advanced clinically stable PH compared with normal subjects.     

Methylated arginines and nitric oxide in end-stage renal disease: impact of inflammation,oxidative stress and haemodialysis

Abstract

Objectives: To determine whether inflammation (C-reactive protein, CRP), oxidative stress (malondialdehyde, MDA) or haemodialysis (HD) affect associations between asymmetric (ADMA), symmetric (SDMA) dimethylarginine, NG-monomethyl-L-arginine (L-NMMA) and nitrite/nitrate (NOx) in end-stage renal disease (ESRD).

Method: Metabolites were measured pre-HD, after 1 hour and end-HD in 40 ESRD patients (age 63?±?14 years).

Results: Positive associations between NOx and ADMA (p?=?0.04), SDMA (p?<?0.001) and L-NMMA (p?=?0.04) were observed pre-HD. Associations weakened during HD but were not significantly influenced by CRP or MDA.

Conclusions: HD, oxidative stress or inflammation did not significantly affect the positive associations between methylated arginines and NOx in ESRD.     

Quantification studies in human seminal plasma samples identify prolactin inducible protein as a plausible marker of azoospermia

Background: Prolactin inducible protein (PIP) is a ~17?kDa protein, which is known to play vital roles in immunoregulation, fertility, antimicrobial activity, apoptosis and tumour progression.

Objectives: This study reports quantification of PIP concentration in human seminal plasma (SP) samples.

Methodology: PIP was purified by immunoprecipitation and its concentration in human SP samples was quantified by ELISA method.

Results: Average concentration of PIP in normozoospermia, oligozoospermia and azoospermia was 290.3?±?71.5 µg/mL, 306.4?±?71.2 µg/mL and 60.5?±?23.6 µg/mL respectively.

Conclusion: There was no significant variation in PIP levels in normozoospermia and oligozoospermia while its expression was down-regulated in azoospermia, indicating that PIP may be a plausible marker of azoospermia.     

Role of diagnostic factors associated with antioxidative status and expression of matrix metalloproteinases (MMPs) in patients with cancer therapy induced ocular disorders

Background

Cancer patients when treated with different chemotherapeutic drugs often develop mild to severe sight threatening diseases during or after chemotherapy. The mechanism involved in the pathogenesis of ocular toxicities is poorly understood. Oxidative stress, inflammation and MMPs (angiogenic factor) are involved in the progression of chemotherapy related ocular disorders.

DNA adducts of ortho-toluidine in human bladder

Background: 4-Aminobiphenyl (4-ABP) and o-toluidine are known human bladder carcinogens, but only 4-ABP-releasing DNA adducts are known.

Methods: Determination of 4-ABP and o-toluidine-releasing DNA adducts in epithelial and submucosal bladder tissues of sudden death victims (SDV: n?=?46), and bladder tumours (n?=?12) by gas chromatography/mass spectrometry.

Results: Above background, 4 and 11 of 12 tumour samples contained adducts of 4-ABP (0.057?±?0.125?fmol/µg DNA) and o-toluidine (8.72?±?4.49?fmol/µg DNA), respectively. Lower adduct levels were present in both epithelial and submucosal bladder tissues of SDV (4-ABP: 0.011?±?0.022 and 0.019?±?0.047?fmol/µg DNA; o-toluidine: 0.24?±?0.63 and 0.27?±?0.70?fmol/µg DNA).

Conclusion: Detection of o-toluidine-releasing DNA adducts support the carcinogenicity of o-toluidine in the human bladder.     

Elevated exhalation of hydrogen peroxide in patients with non-small cell lung cancer is not affected by chemotherapy

Objectives: Reactive oxygen species, which are implicated in the process of carcinogenesis, are also responsible for cell death during chemotherapy (CHT). Therefore, the aim of the study was to evaluate exhaled H₂O₂ levels in non-small cell lung cancer (NSCLC) patients before and after CHT.

Methods: Thirty patients (age 61.3?±?9.3 years) with advanced NSCLC (stage IIIB–IV) and 15 age-matched healthy cigarette smokers were enrolled into the study. Patients received four cycles of cisplatin or carboplatin with vinorelbine every three weeks. Before and after the first, second, and fourth cycle, the concentration of H₂O₂ in exhaled breath condensate was measured with respect to treatment response.

Results: At the baseline, NSCLC patients exhaled 3.8 times more H₂O₂ than the control group (0.49?±?0.14 vs. 0.13?±?0.03?µmol/L, P?2O₂ levels independent of the treatment response (partial remission vs. progressive disease). Pre- and post-CHT cycles of H₂O₂ levels generally correlated positively.

Discussion: The study demonstrated the occurrence of oxidative stress in the airways of advanced NSCLC patients. Exhaled H₂O₂ level was not affected by CHT and independent of treatment results and changes in the number of circulating neutrophils.     

Comparison of β2-microglobulin serum level between Alzheimer’s patients,cognitive healthy and mild cognitive impaired individuals

Background: Several studies performed in the last years on the brain, showed that beta2-microglobulin (β2m) and MHC can act independently of their canonical immune function to regulate normal brain development, synaptic plasticity and behaviour. Increased systemic levels of soluble β2m have been implicated in cognitive impairments like that associated with chronic haemodialysis, or aortic valve replacement. Increased soluble β2m has also been detected in the cerebral spinal fluid (CSF) of patients with HIV-associated dementia and Alzheimer’s disease (AD).

Objective: To compare plasma β2m levels in healthy subjects and subjects with dementia or cognitive impairment.

Methods: We measured the concentration of β2m in a cohort of 245 individuals and compared sex matched, cognitive healthy individuals.

Results: We found higher levels of β2m in AD patients compared to non-AD MCI and healthy controls (2063?ng/mL ±852 versus 1613?±?503 and 1832?±?382?ng/mL, pp?>?0.05).

Conclusions: Our data confirm that β2m could play a role in AD. However, a replication study in an independent cohort would be necessary to confirm our preliminary results.     

Dim Light Melatonin Onset in Alcohol-Dependent Men and Women Compared with Healthy Controls

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean?±?SD age: 36.0?±?11.0 yrs of age, 10 women) who were 3–12 wks since their last drink (abstinence: 57.9?±?19.3 d) and 19 age- and sex-matched HCs (34.4?±?10.6 yrs, 5 women). Following a 23:00–06:00?h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00?h bedtime) during which salivary melatonin samples were collected every 30?min beginning at 19:30?h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02?±?00:41?h, than in HC, 20:44?±?00:21?h (t?=??2.4, p?=?.02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18?min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats. (Author correspondence: daconroy@med.umich.edu)     

Increase of reactive oxygen species in different tissues during lipopolysaccharide-induced fever and antipyresis: an electron paramagnetic resonance study

Abstract

Fever is a regulated increase in body temperature and a component of the acute-phase response, triggered mainly after the invasion of pathogens in the body. Reactive oxygen species (ROS) are generated during the physiological and pathological processes, and can act as both signalling molecules as well as promoters of oxidative stress. Male Wistar rats, pretreated with oral doses of acetaminophen, celecoxib, dipyrone, or ibuprofen 30?min before an intravenous lipopolysaccharide (LPS) or sterile saline injection, showed a reduced febrile response in all animals tested. The formation of ROS in the fresh blood, liver, brown adipose tissue (BAT), and hypothalamus of febrile and antipyretic-treated animals was assessed by electron paramagnetic resonance using the spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH). While the CM^? concentrations remained unaltered in the blood samples examined 5?h after the induction of fever, we found increased CM^? levels in the liver (in µM, saline: 290?±?42; LPS: 512?±?34), BAT (in µM, saline: 509?±?79, LPS: 855?±?79), and hypothalamus (in µM, saline: 292?±?35; LPS: 467?±?8) at the same time point. Importantly, none of the antipyretics were seen to alter the CM^? accumulation profile. Data from this study suggest that there is an increased formation of ROS in the different tissues during fever, which may cause oxidative stress, and that the antipyretics tested do not interfere with ROS production.     

Gonadal response after a single-dose stimulation test with recombinant human chorionic gonadotropin (rhCG) in patients with isolated prepubertal cryptorchidism

Background

The evaluation of prepubertal gonadal Leydig cells secretion requires gonadotropin stimulation. Urinary hCG (human chorionic gonadotropin) is currently unavailable in many countries, however, recombinant hCG (rhCG) can be used. Our aim was to evaluate rhCG-stimulated testicular hormones in a group of patients with cryptorchidism.

Methods

We evaluated 31 prepubertal boys (age range, 0.75–9.0 years) presenting with unilateral (n?=?24) or bilateral (n?=?7) cryptorchidism. Patients with other genital abnormalities, previous use of hCG or testosterone or previous surgeries were excluded. Blood samples were obtained at baseline and 7 days after a single subcutaneous dose of rhCG (Ovidrel® 250 mcg) to measure the testosterone, DHT (dihydrotestosterone), AMH (anti-Mullerian hormone), and inhibin B levels.

Results

rhCG stimulation significantly increased testosterone levels from 10 ng/dl to 247.8?±?135.8 ng/dl, increased DHT levels from 4.6?±?0.8 to 32.3?±?18.0 ng/dl, and increased the T/DHT ratio from 2.2?±?0.4 to 8.0?±?3.5. There was also a significant increase in inhibin B (from 105.8?±?65.2 to 132.4?±?56.1 pg/ml; p?<?0.05) and AMH levels (from 109.4?±?52.6 to 152.9?±?65.2 ng/ml; p?<?0.01) after the rhCG stimulation.

Conclusions

In this cohort, hormonal responses can be elicited after the rhCG stimulation test, suggesting that rhCG is a promising stimulation test to replace the urinary hCG test during the evaluation of gonadal Leydig cells function. The clinical applicability and adequate performance of rhCG testing must be investigated in future studies.