Papillary atrophy of the tongue and nutritional status of hospitalized alcoholics

BACKGROUND: Atrophy of the papillae, mucosa, and dorsum of the tongue are considered classical signs of nutritional deficiencies. OBJECTIVE: To assess the nutritional status of hospitalized alcoholics with or without papillary atrophy of the tongue. METHODS: This study was performed with 21 hospitalized alcoholics divided into Atrophic Glossitis Group (n=13) and Normal Tongue Group (n=8). Healthy, non-alcoholic volunteers composed the Control Group (n=8). Anthropometry and bioelectric impedance were performed, and serum vitamins A, E, and B12 were determined. RESULTS: There were no statistical differences in relation to age (46.7±8.7 vs. 46.8±15.8 years) or gender (92.3% vs. 87.5% male), respectively. Control Group volunteers were also paired in relation to age (47.5±3.1 years) and male predominance (62.5%). In relation to hospitalized alcoholics without atrophic lesions of the tongue and Control Group, patients with papillary atrophy showed lower BMI (18.6 ± 2,5 vs 23.8 ± 3.5 vs 26.7 ± 3,6 kg/m² ) and body fat content 7.6 ± 3.5 vs 13.3 ± 6.5 vs 19.5 ± 4,9 kg). When compared with the Control Group, alcoholic patients with or without papillary atrophy of the tongue showed lower values of red blood cells (10.8 ± 2.2 vs 11.8 ± 2.2 vs 14.5 ± 1,6g/dL) and albumin (3.6 ± 0.9 vs 3.6 ± 0.8 vs 4.4 ± 0.2g/dL). The seric levels of vitamins A, E, and B12 were similar amongst the groups. CONCLUSION: Hospitalized alcoholics with papillary atrophy of the tongue had lower BMI and fat body stores than controls, without associated hypovitaminosis.

Leucine and HMB differentially modulate proteasome system in skeletal muscle under different sarcopenic conditions

In the present study we have compared the effects of leucine supplementation and its metabolite β-hydroxy-β-methyl butyrate (HMB) on the ubiquitin-proteasome system and the PI3K/Akt pathway during two distinct atrophic conditions, hindlimb immobilization and dexamethasone treatment. Leucine supplementation was able to minimize the reduction in rat soleus mass driven by immobilization. On the other hand, leucine supplementation was unable to provide protection against soleus mass loss in dexamethasone treated rats. Interestingly, HMB supplementation was unable to provide protection against mass loss in all treatments. While solely fiber type I cross sectional area (CSA) was protected in immobilized soleus of leucine-supplemented rats, none of the fiber types were protected by leucine supplementation in rats under dexamethasone treatment. In addition and in line with muscle mass results, HMB treatment did not attenuate CSA decrease in all fiber types against either immobilization or dexamethasone treatment. While leucine supplementation was able to minimize increased expression of both Mafbx/Atrogin and MuRF1 in immobilized rats, leucine was only able to minimize Mafbx/Atrogin in dexamethasone treated rats. In contrast, HMB was unable to restrain the increase in those atrogenes in immobilized rats, but in dexamethasone treated rats, HMB minimized increased expression of Mafbx/Atrogin. The amount of ubiquitinated proteins, as expected, was increased in immobilized and dexamethasone treated rats and only leucine was able to block this increase in immobilized rats but not in dexamethasone treated rats. Leucine supplementation maintained soleus tetanic peak force in immobilized rats at normal level. On the other hand, HMB treatment failed to maintain tetanic peak force regardless of treatment. The present data suggested that the anti-atrophic effects of leucine are not mediated by its metabolite HMB.

Exercise and caloric restriction alter the immune system of mice submitted to a high-fat diet

As the size of adipocytes increases during obesity, the establishment of resident immune cells in adipose tissue becomes an important source of proinflammatory mediators. Exercise and caloric restriction are two important, nonpharmacological tools against body mass increase. To date, their effects on the immune cells of adipose tissue in obese organisms, specifically when a high-fat diet is consumed, have been poorly investigated. Thus, after consuming a high-fat diet, mice were submitted to chronic swimming training or a 30% caloric restriction in order to investigate the effects of both interventions on resident immune cells in adipose tissue. These strategies were able to reduce body mass and resulted in changes in the number of resident immune cells in the adipose tissue and levels of cytokines/chemokines in serum. While exercise increased the number of NK cells in adipose tissue and serum levels of IL-6 and RANTES, caloric restriction increased the CD4+/CD8+ cell ratio and MCP-1 levels. Together, these data demonstrated that exercise and caloric restriction modulate resident immune cells in adipose tissues differently in spite of an equivalent body weight reduction. Additionally, the results also reinforce the idea that a combination of both strategies is better than either individually for combating obesity

Correlation between insulin resistance and treatment-resistant acne

Physiologically during puberty and adolescence, when juvenile acne usually appears, the response to a glucose load is increased if compared to the one observed in adult and at pre-pubertal age, while insulin sensitivity is reduced. Insulin is a hormone that acts at different levels along the axis which controls the sex hormones. It increases the release of LH and FSH by pituitary gland, stimulates the synthesis of androgens in the gonads and stimulates the synthesis of androgenic precursors in adrenal glands. Finally, it acts in the liver by inhibiting the synthesis of Sex Hormone Binding Globulin (SHBG). Insulin is also able to act directly on the production of sebum and amplify the effects of Iinsulin Growth Factor-1 in the skin, inhibiting the synthesis of its binding protein (IGF Binding Protein-1). In female subjects with acne and Polycystic Ovary Syndrome (PCOS) insulin resistance is a well known pathogenetic factor, while the relationship between acne and insulin resistance has been poorly investigated in males so far. The purpose of this study is to investigate the correlation between insulin resistance and acne in young males who do not respond to common therapies. Clinical and biochemical parameters of glucose, lipid metabolism, androgens and IGF-1 were evaluated. Insulin resistance was estimated by Homeostasis Model assessment (HOMA-IR) and Oral Glucose Tolerance Test was also performed. We found that subjects with acne had higher Sistolic and Diastolic Blood Pressure, Waist/Hip Ratio, Waist Circumference, 120' OGTT serum insulin and serum IGF-1 and lower HDL-cholesterol than subjects of comparable age and gender without acne. The results thus obtained confirmed what other authors have recently reported about a metabolic imbalance in young males with acne. Furthermore, these results support the hypothesis that insulin resistance might play an important role in the pathogenesis of treatment-resistant acne in males.

Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis

Energy-dependent intestinal calcium absorption is important for the maintenance of calcium and bone homeostasis, especially when dietary calcium supply is restricted. The active form of vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], is a crucial regulator of this process and increases the expression of the transient receptor potential vanilloid 6 (Trpv6) calcium channel that mediates calcium transfer across the intestinal apical membrane. Genetic inactivation of Trpv6 in mice (Trpv6(-/-)) showed, however, that TRPV6 is redundant for intestinal calcium absorption when dietary calcium content is normal/high and passive diffusion likely contributes to maintain normal serum calcium levels. On the other hand, Trpv6 inactivation impaired the increase in intestinal calcium transport following calcium restriction, however without resulting in hypocalcemia. A possible explanation is that normocalcemia is maintained at the expense of bone homeostasis, a hypothesis investigated in this study. In this study, we thoroughly analyzed the bone phenotype of Trpv6(-/-) mice receiving a normal (approximately 1%) or low (approximately 0.02%) calcium diet from weaning onwards using micro-computed tomography, histomorphometry and serum parameters. When dietary supply of calcium is normal, Trpv6 inactivation did not affect growth plate morphology, bone mass and remodeling parameters in young adult or aging mice. Restricting dietary calcium had no effect on serum calcium levels and resulted in a comparable reduction in bone mass accrual in Trpv6(+/+) and Trpv6(-/-) mice (-35% and 45% respectively). This decrease in bone mass was associated with a similar increase in bone resorption, whereas serum osteocalcin levels and the amount of unmineralized bone matrix were only significantly increased in Trpv6(-/-) mice. Taken together, our findings indicate that TRPV6 contributes to intestinal calcium transport when dietary calcium supply is limited and in this condition indirectly regulates bone formation and/or mineralization.

Impact of differential P450c17 phosphorylation by cAMP stimulation and by starvation conditions on enzyme activities and androgen production in NCI-H295R cells

CYP17A1 plays a pivotal role in the biosynthesis of androgens in the adrenals and the gonads. Although this enzyme catalyzes two different reactions on one single active site, its specific activities are regulated independently. Although the 17alpha-hydroxylase activity is rather constant and regulated by gene expression, the 17,20-lyase activity varies significantly with the amount of cofactors or by protein phosphorylation. cAMP increases CYP17A1 expression, P450c17 phosphorylation, and androgen production. However, the exact mechanism(s) and the specific regulators of CYP17A1 remain unknown. Therefore, we studied the regulation of adrenal androgen biosynthesis in human adrenal H295R cells focusing on CYP17A1. We analyzed androgen production and P450c17 activities in H295R cells grown under normal and serum-free conditions and/or after stimulation with 8-bromoadenosine-cAMP. H295R cells grown in starvation medium produced more androgens and had decreased HSD3B2 expression and activity but increased P450c17-17,20-lyase activity and serine phosphorylation. Although starvation increased serine phosphorylation of P450c17 specifically, cAMP stimulation enhanced threonine phosphorylation exclusively. Time-course experiments revealed that a short cAMP stimulation augmented threonine phosphorylation of P450c17 but did not increase 17,20-lyase activity. By contrast, long cAMP stimulation increased androgen production through increased P450c17 activities by enhancing CYP17A1 gene expression. We conclude that serum withdrawal shifts steroidogenesis of H295R cells towards androgen production, providing a suitable model for detailed studies of androgen regulation. In addition, our study shows that starvation and cAMP stimulation regulate P450c17 phosphorylation differentially and that an increase in P450c17 phosphorylation does not necessarily lead to enhanced enzyme activity and androgen production.

Saliva/pathogen biomarker signatures and periodontal disease progression

The purpose of this study was to determine the role of saliva-derived biomarkers and periodontal pathogens during periodontal disease progression (PDP). One hundred human participants were recruited into a 12-month investigation. They were seen bi-monthly for saliva and clinical measures and bi-annually for subtraction radiography, serum and plaque biofilm assessments. Saliva and serum were analyzed with protein arrays for 14 pro-inflammatory and bone turnover markers, while qPCR was used for detection of biofilm. A hierarchical clustering algorithm was used to group study participants based on clinical, microbiological, salivary/serum biomarkers, and PDP. Eighty-three individuals completed the six-month monitoring phase, with 39 [corrected] exhibiting PDP, while 44 [corrected] demonstrated stability. Participants assembled into three clusters based on periodontal pathogens, serum and salivary biomarkers. Cluster 1 members displayed high salivary biomarkers and biofilm; 71% [corrected] of these individuals were undergoing PDP. Cluster 2 members displayed low biofilm and biomarker levels; 76% [corrected] of these individuals were stable. Cluster 3 members were not discriminated by PDP status; however, cluster stratification followed groups 1 and 2 based on thresholds of salivary biomarkers and biofilm pathogens. The association of cluster membership to PDP was highly significant (p < 0.0007). [corrected] The use of salivary and biofilm biomarkers offers potential for the identification of PDP or stability (ClinicalTrials.gov number, CT00277745).

Massive Systemic Fat Embolism Detected by Postmortem Imaging and Biopsy

Postmortem computed tomography (pmCT) and pmCT angiography (pmCTA) provide a minimally invasive method to determine the cause of death. Postmortem image-guided biopsy allows for precise sampling of histological specimens. This case study describes the findings of lethal systemic fat embolism (FE) on whole-body unenhanced pmCT, pmCTA, and image-guided biopsy, with autopsy and histopathologic correlation. Unenhanced pmCT revealed a distinct fat level on top of sedimented layers of corpuscular blood particles and serum in the arterial system and pulmonary trunk. Subsequent pmCTA showed reproducible results, and image-guided biopsy confirmed fatal FE. pm CT/pmCTA combined with image-guided biopsy established the cause of death as right heart failure as a result of systemic fatal FE prior to autopsy. All imaging findings were consistent with traditional autopsy and histological specimens. This unique case demonstrates new imaging findings in massive, fatal FE and highlights that postmortem imaging, supplemented by image-guided biopsy, may detect the cause of death prior to traditional autopsy.

Pentraxins and atherosclerosis: the role of PTX3

Pentraxins are a family of evolutionarily conserved multifunctional pattern-recognition proteins characterized by a cyclic multimeric structure. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the liver in response to IL-6, while PTX3 is produced by a variety of tissues and cells and in particular by innate immunity cells in response to proinflammatory signals and Toll-like receptor (TLR) engagement. PTX3 interacts with several ligands, including growth factors, extracellular matrix components and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes, acting as a predecessor of antibodies. In addition, PTX3 is essential in female fertility by acting as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Here we will concisely review the general properties of PTX3 in the context of the pentraxin superfamily and discuss recent data suggesting that PTX3 plays a cardiovascular protective effect. PTX3 may represent a new marker in vascular pathology which correlates with the risk of developing vascular events.

Lipid profiles and outcome in patients treated by intravenous thrombolysis for cerebral ischemia

OBJECTIVE:To determine whether low low-density lipoprotein cholesterol (LDL-C) but not high-density lipoprotein cholesterol (HDL-C) and triglyceride concentrations are associated with worse outcome in a large cohort of ischemic stroke patients treated with IV thrombolysis. METHODS:Observational multicenter post hoc analysis of prospectively collected data in stroke thrombolysis registries. Because of collinearity between total cholesterol (TC) and LDL-C, we used 2 different models with TC (model 1) and with LDL-C (model 2). RESULTS:Of the 2,485 consecutive patients, 1,847 (74%) had detailed lipid profiles available. Independent predictors of 3-month mortality were lower serum HDL-C (adjusted odds ratio [(adj)OR] 0.531, 95% confidence interval [CI] 0.321-0.877 in model 1; (adj)OR 0.570, 95% CI 0.348-0.933 in model 2), lower serum triglyceride levels ((adj)OR 0.549, 95% CI 0.341-0.883 in model 1; (adj)OR 0.560, 95% CI 0.353-0.888 in model 2), symptomatic ICH, and increasing NIH Stroke Scale score, age, C-reactive protein, and serum creatinine. TC, LDL-C, HDL-C, and triglycerides were not independently associated with symptomatic ICH. Increased HDL-C was associated with an excellent outcome (modified Rankin Scale score 0-1) in model 1 ((adj)OR 1.390, 95% CI 1.040-1.860). CONCLUSION:Lower HDL-C and triglycerides were independently associated with mortality. These findings were not due to an association of lipid concentrations with symptomatic ICH and may reflect differences in baseline comorbidities, nutritional state, or a protective effect of triglycerides and HDL-C on mortality following acute ischemic stroke.

Adipocytokines, hepatic and inflammatory biomarkers and incidence of type 2 diabetes. the CoLaus study

Context There is contradictory information regarding the prognostic importance of adipocytokines, hepatic and inflammatory biomarkers on the incidence of type 2 diabetes. The objective was to assess the prognostic relevance of adipocytokine and inflammatory markers (C-reactive protein – CRP; interleukin-1beta – IL-1β; interleukin-6– IL-6; tumour necrosis factor-α – TNF-α; leptin and adiponectin) and gamma-glutamyl transpeptidase (γGT) on the incidence of type 2 diabetes. Methods Prospective, population-based study including 3,842 non-diabetic participants (43.3% men, age range 35 to 75 years), followed for an average of 5.5 years (2003–2008). The endpoint was the occurrence of type 2 diabetes. Results 208 participants (5.4%, 66 women) developed type 2 diabetes during follow-up. On univariate analysis, participants who developed type 2 diabetes had significantly higher baseline levels of IL-6, CRP, leptin and γGT, and lower levels of adiponectin than participants who remained free of type 2 diabetes. After adjusting for a validated type 2 diabetes risk score, only the associations with adiponectin: Odds Ratio and (95% confidence interval): 0.97 (0.64–1.47), 0.84 (0.55–1.30) and 0.64 (0.40–1.03) for the second, third and forth gender-specific quartiles respectively, remained significant (P-value for trend = 0.05). Adding each marker to a validated type 2 diabetes risk score (including age, family history of type 2 diabetes, height, waist circumference, resting heart rate, presence of hypertension, HDL cholesterol, triglycerides, fasting glucose and serum uric acid) did not improve the area under the ROC or the net reclassification index; similar findings were obtained when the markers were combined, when the markers were used as continuous (log-transformed) variables or when gender-specific quartiles were used. Conclusion Decreased adiponectin levels are associated with an increased risk for incident type 2 diabetes, but they seem to add little information regarding the risk of developing type 2 diabetes to a validated risk score.

Suppression of transforming growth factor beta signalling aborts caerulein induced pancreatitis and eliminates restricted stimulation at high caerulein concentrations

BACKGROUND: Transforming growth factors betas (TGF-betas) are implicated in pancreatic tissue repair but their role in acute pancreatitis is not known. To determine whether endogenous TGF-betas modulate the course of caerulein induced acute pancreatitis, caerulein was administered to wild-type (FVB-/-) and transgenic mice that are heterozygous (FVB+/-) for expression of a dominant negative type II TGF-beta receptor. METHODS: After 7 hourly supramaximal injections of caerulein, the pancreas was evaluated histologically and serum was assayed for amylase and lipase levels. Next, the effects of caerulein on amylase secretion were determined in mouse pancreatic acini, and cholecystokinin (CCK) receptor expression was assessed. RESULTS: The normal mouse pancreas was devoid of inflammatory cells whereas the pancreas from transgenic mice contained lymphocytic infiltrates. Caerulein injection in wild-type mice resulted in 6- and 36-fold increases in serum amylase and lipase levels, respectively, increased serum trypsinogen activation peptide (TAP) levels, gross oedema and a marked inflammatory response in the pancreas that consisted mainly of neutrophils and macrophages. By contrast, FVB+/- mice exhibited minimal alterations in response to caerulein with attenuated neutrophil-macrophage infiltrates. Moreover, acini from FVB+/- mice did not exhibit restricted stimulation at high caerulein concentrations, even though CCK receptor mRNA levels were not decreased. CONCLUSION: Our findings indicate that a functional TGF-beta signalling pathway may be required for caerulein to induce acute pancreatitis and for the CCK receptor to induce acinar cell damage at high ligand concentrations. Our results also support the concept that restricted stimulation at high caerulein concentrations contributes to the ability of caerulein to induce acute pancreatitis.

Factor XIII activation peptide is released into plasma upon cleavage by thrombin and shows a different structure compared to its bound form

The first step of coagulation factor XIII (FXIII) activation involves cleavage of the FXIII activation peptide (FXIII-AP) by thrombin. However, it is not known whether the FXIII-AP is released into plasma upon cleavage or remains attached to activated FXIII. The aim of the present work was to study the structure of free FXIII-AP, develop an assay for FXIII-AP determination in human plasma, and to answer the question whether FXIII-AP is released into plasma. We used ab-initio modeling and molecular dynamics simulations to study the structure of free FXIII-AP. We raised monoclonal and polyclonal antibodies against FXIII-AP and developed a highly sensitive and specific ELISA method for direct detection of FXIII-AP in human plasma. Structural analysis showed a putative different conformation of the free FXIII-AP compared to FXIII-AP bound to the FXIII protein. We concluded that it might be feasible to develop specific antibodies against the free FXIII-AP. Using our new FXIII-AP ELISA, we found high levels of FXIII-AP in in-vitro activated plasma samples and serum. We showed for the first time that FXIIIAP is detached from activated FXIII and is released into plasma, where it can be directly measured. Our findings may be of major clinical interest in regard to a possible new marker in thrombotic disease.

Correlates of periodontal decline and biologic markers in older adults

BACKGROUND: There is limited information on infectious and host responses distinguishing older people with or without active periodontitis. This study measured bacterial and serum cytokine and high-sensitivity C-reactive protein (hsCRP) levels in older persons. METHODS: Elders (mean age: 67 years), whose periodontal status had declined most or least (20% worst or 20% best) over 5 years, were enrolled. Two years later, they were classified as periodontally declining (active periodontitis [AP]), if they had at least five teeth with probing depth (PD) > or =5 mm, or stable (stable periodontally [SP]), if they did not. Groups were compared with respect to demographics, PD, clinical loss of attachment, subgingival bacteria, serum hsCRP, interleukin (IL)-1beta and -6, and chronic diseases. RESULTS: Ten AP and 24 SP subjects were identified; 13% of women and 44% of men from the original sample were in the AP group (P <0.05). Most Asians were SP; most whites and all African Americans were classified as having AP (P <0.01). More AP elders had osteoporosis (P <0.01), but the AP and SP groups did not differ with respect to IL-1beta and -6 or hsCRP. Bacterial counts were higher in the AP group for Parvimonas micra (previously Peptostreptococcus micros or Micromonas micros) (7.7 x 10(5) cells versus 3.8 x 10(5) cells; P <0.05), Prevotella intermedia (25.7 x 10(5) cells versus 9.8 x 10(5) cells; P <0.01), Tannerella forsythia (previously T. forsythensis) (16.2 x 10(5) cells versus 8.0 x 10(5) cells; P <0.05), and Streptococcus mutans (6.2 x 10(5) cells versus 2.0 x 10(5) cells; P <0.01). Three risk factors were most predictive of periodontal decline: PD, osteoporosis, and being white or African American. CONCLUSION: Periodontal decline was associated with osteoporosis, ethnicity, PD, gender, serum hsCRP, and levels of four bacterial species.

Sphingosine kinase 1 is pivotal for Fc epsilon RI-mediated mast cell signaling and functional responses in vitro and in vivo

Mast cell degranulation is pivotal to allergic diseases; investigating novel pathways triggering mast cell degranulation would undoubtedly have important therapeutic potential. FcepsilonRI-mediated degranulation has contradictorily been shown to require SphK1 or SphK2, depending on the reports. We investigated the in vitro and in vivo specific role(s) of SphK1 and SphK2 in FcepsilonRI-mediated responses, using specific small interfering RNA-gene silencing. The small interfering RNA-knockdown of SphK1 in mast cells inhibited several signaling mechanisms and effector functions, triggered by FcepsilonRI stimulation including: Ca(2+) signals, NFkappaB activation, degranulation, cytokine/chemokine, and eicosanoid production, whereas silencing SphK2 had no effect at all. Moreover, silencing SPHK1 in vivo, in different strains of mice, strongly inhibited mast cell-mediated anaphylaxis, including inhibition of vascular permeability, tissue mast cell degranulation, changes in temperature, and serum histamine and cytokine levels, whereas silencing SPHK2 had no effect and the mice developed anaphylaxis. Our data differ from a recent report using SPHK1(-/-) and SPHK2(-/-) mice, which showed that SphK2 was required for FcepsilonRI-mediated mast cell responses. We performed experiments in mast cells derived from SPHK1(-/-) and SPHK2(-/-) mice and show that the calcium response and degranulation, triggered by FcepsilonRI-cross-linking, is not different from that triggered in wild-type cells. Moreover, IgE-mediated anaphylaxis in the knockout mice showed similar levels in temperature changes and serum histamine to that from wild-type mice, indicating that there was no protection from anaphylaxis for either knockout mice. Thus, our data strongly suggest a previously unrecognized compensatory mechanism in the knockout mice, and establishes a role for SphK1 in IgE-mediated mast cell responses.