Salivary biochemical parameters in people living with HIV on ART and dental caries: a cross-sectional study in Monastir, Tunisia.

BACKGROUND: Studies regarding salivary biochemical parameters and dental caries in adult people living with HIV/AIDS (PLWHA) are scanty. AIM: To investigate salivary biochemical parameters and dental caries in adult PLWHA who are on antiretroviral therapy (ART) and compare the findings with people negative for HIV infection. METHODS: The study included 50 HIV positive individuals as a test group (TG) and 50 HIV negative individuals as a control group (CG). Dental examination was performed according to WHO guidelines to assess DMFT. Digital panoramic radiographs were taken to detect additional infectious foci. Non-stimulated saliva was collected between 9 and 12 a. m for 5 min to evaluate 18 biochemical parameters and salivary flow rate (SFR). Parametric and non parametric tests were used according to data distribution. The level of significance was set at p < 0.05%. RESULTS: Patients' mean ages and M/F sex ratios for TG and CG were 38.80 ± 9.69 y/o. vs. 37.98 ± 13.47 y/o. and 3.54 vs. 2.33, respectively. Higher means of decayed teeth were recorded in TG, 4.47 ± 3.00 vs. 3.88 ± 2.81 in CG with no significant difference (p = 0.41). Means of filled teeth were significantly lower in TG 2.38 ± 2.16 vs. 4.16 ± 3.35 in CG (p = 0.01), respectively. No statistical significant difference was noted in DMFT indices between the 2 groups (8.04 ± 6.90 vs. 8.52 ± 6.24, p = 0.71). The following salivary parameters were significantly lower in TG compared to CG, respectively: mean SFR 0.44 ± 0.18 ml/min vs. 0.61 ± 0.26 ml/min; median levels of sodium and chlorides, 4 mmol/L and 13.5 mmol/L vs. 9 mmol/L and 19 mmol/L (p < 0.001) and uric acid, 103.50 mmol/L vs. 163 (p = 0.009). However, higher median levels were recorded with calcium, 1.09 mmol/L vs. 0.54 (p < 0.001) and sIgA 23 mg/dl vs. 5 mg/dl (p < 0.001). In TG, a positive correlation was found between DC, potassium, urea, and chlorides (p < 0.05). Salivary renal and hepatic biomarkers were comparable between the two groups. CONCLUSIONS: PLWHA have shown an alteration in some salivary parameters, more decayed teeth and less filled teeth. Preventive measures should be implemented to lower dental caries and enhance accessibility to oral care services. In addition, saliva can be utilized to monitor oral and general health status among PLWHA on ART.

Postnatal exposure to Bisphenol S induces liver injury in mice: Possible implication of PPARγ receptor.

There is considerable evidence that Bisphenol S (BPS) induces various toxicological effects and is an industrial health issue. However, little data are available on the in vivo effects of BPS on the liver, a major target of drug toxicity. In this study, we evaluated the potential harmfulness of low levels of BPS in the liver of male mice. Also, we investigated the interaction between BPS and peroxisome proliferator-activated receptor-gamma (PPARγ) by computational docking approach. PPARγ is a member of the superfamily of nuclear hormone receptors. It acts as a transcription factor and regulates the genes involved in lipid and glucose metabolism and in inflammation and necrosis. Mice were exposed to BPS, in drinking water at 25, 50, and 100 µg/kg for 10 weeks. The protocol was started after weaning. At the time of sacrifice, blood samples were collected for a biochemical analysis, followed by liver tissue collection for histopathological study. Results showed that BPS-induced hypertriglyceridemia, increased liver injury markers, and initiated histopathological changes, including inflammatory cell infiltration, hepatocellular necrosis, and steatosis. BPS did not affect glycated hemoglobin (HbA1C). Interestingly, data showed that BPS could interact with the PPARγ ligand-binding pocket by hydrogen bonds with Asn 219, Cys 276, Ser 280, and Thr 283. We suggest that PPARγ is among the targets of BPS and could play a key role in the cascade reaction of BPS-induced liver disruption. These findings support the hypothesis that the post-weaning period is sensitive to low-dose BPS exposure that can lead to dyslipidemia signature later in life.

Novel association between apoptotic sperm biomarkers with seminal biochemical parameters and acetylcholinesterase activity in patients with teratozoospermia.

OBJECTIVE: We aimed to determine whether the dysfunction of physiological apoptosis and specific seminal biochemical parameters could be associated with male infertility and sperm morphological defects. STUDY DESIGN: Ejaculated sperm samples from sixty patients with isolated teratozoospermia and thirty fertile donors were analyzed. The proportion of both viable and dead spermatozoa expressing activated caspases was detected by fluorescence microscopy through the use of different specific carboxyfluorescein-labeled caspase inhibitors FLICA. The different stages of apoptosis in human were qualitatively and quantitatively determined by using the AO/EB fluorescent staining method. The levels of the seminal biochemical parameters (acetylcholinesterase (AChE), lactate dehydrogenase (LDH), creatine phosphokinase (CK), iron (Fe), calcium (Ca), and phosphorus (P)) were evaluated spectrophotometrically. RESULTS: Patients with teratozoospermia showed significantly higher proportions of dead and live spermatozoa with activated caspases and spermatozoa in the late stage of apoptosis when compared to controls. Among the different studied biochemical seminal parameters, the rates of acetylcholinesterase activity, creatine phosphokinase, iron, and calcium were significantly increased in the patient group. However, the rate of phosphorus was significantly decreased. Interestingly, significant relationships were found between the studied biochemical and apoptotic biomarkers and the rates of atypical sperm forms with the incidences of head, mid-piece, and tail abnormalities. Furthermore, positive correlations were found between P, AChE, Fe, CK, and LDH with apoptotic markers. CONCLUSIONS: These results emphasize the impact of apoptosis in the pathophysiology of teratozoospermia and suggest that seminal biochemical disturbance may arise such damage.

Metal-Organic Frameworks as Efficient Oral Detoxifying Agents.

Poisoning and accidental oral intoxication are major health problems worldwide. Considering the insufficient efficacy of the currently available detoxification treatments, a pioneering oral detoxifying adsorbent agent based on a single biocompatible metal-organic framework (MOF) is here proposed for the efficient decontamination of drugs commonly implicated in accidental or voluntary poisoning. Furthermore, the in vivo toxicity and biodistribution of a MOF via oral administration have been investigated for the first time. Orally administered upon a salicylate overdose, this MOF is able to reduce the salicylate gastrointestinal absorption and toxicity more than 40-fold (avoiding histological damage) while exhibiting exceptional gastrointestinal stability (<9% degradation), poor intestinal permeation, and safety.

Resistin polymorphims, plasma resistin levels and obesity in Tunisian volunteers.

BACKGROUND: Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Resistin (RETN); it's an adipocytes-secreted cytokine and has been proposed as a link between obesity and diabetes. Many resistin gene polymorphisms were described and their implication in obesity was controversial. This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in RETN gene 420C/G; 44G/A; 62G/A; 394C/G and 299 G/A and their association with Resistin level and obesity in Tunisian volunteers. METHODS: We recruited 169 nonobese (mean age=42.16-14.26 years; mean body mass index [BMI]=24.51-3.69 kg/m2 ) and 160 obese (mean age=47.86-11.17 years; mean BMI=36-4.78 kg/m2 ). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. Anthropometric parameters, lipid levels, Glycemia and insulinemia were measured, BMI was calculated and insulinresistance was evaluated with the homeostasis model assessment insulin resistance (HOMA-IR) and resistin level was measured by ELISA. Statistical analyses were performed by SPSS19.0. RESULTS: After adjustment for confounding parameters; the Odds Ratio (OR) of obesity associated with mutated genotypes at 420C/G compared with normal genotype was as: OR=2.17; 95% CI [1.28-3.68], P=.004. The serum Resistin levels present no significant association with all RETN polymorphisms and it was significantly associated with BMI (P=.047). In our haplotype analysis, one haplotype seems to be protective and one other seems to be the highest risk to obesity. CONCLUSION: The 420 C/G Polymorphism were associated with obesity and Leptin concentration in our population.

Osteoprotegerin as a marker of cardiovascular risk in children and adolescents with type 1 diabetes.

BACKGROUND: Elevated osteoprotegerin (OPG) levels have been reported in patients with diabetes complications. We investigated whether plasma OPG levels can be used as a marker of cardiovascular risk in children and adolescents with type 1 diabetes (T1D). METHODS: Plasma blood samples were obtained from 243 subjects (143 children and adolescents with T1D and 100 healthy controls). OPG concentrations were measured by enzyme-linked immunosorbent assay (ELISA) method. All data were analyzed by using PASW statistics 18. RESULTS: A significant higher plasma OPG level was found in children with T1D compared to controls (p < 0.001). A significant increase of OPG levels has been related to the glucose level ≥ 7 mmol/L (2.44 [0.01-6.22] vs. 2.16 [0.13-6.22] pmol/L, p = 0.019), microalbuminuria ≥ 30 mg/24 h (3.71 [0.160-6.03] vs. 2.26 [0.01-6.22] pmol/L, p < 0.001), and cystatin-C ≥ 0.789 mg/L (2.64 [0.37-6.22] vs. 2.11 [0.01-5.82] pmol/L, p < 0.001). We noted a significant higher frequency of children with increased cystatin-C levels in the group with elevated plasma level of OPG compared with those with normal levels (49 vs. 18%, respectively) with an odds ratio (OR) = 4.42 [1.41-13.84] (p = 0.006). We showed a significant increase of OPG levels when the number of cardiovascular risk factors exceeds 3 (p = 0.001). CONCLUSION: OPG may be a potential biomarker of cardiovascular risk in T1D. Implementation of OPG determination in the clinical laboratory setting would be useful in order to better stratify patients and to assess the most adequate treatment.

Genetic Variation in the Renin-Angiotensin System and Diabetic Nephropathy in the Tunisian Population.

BACKGROUND: The aim of this study was to evaluate the association of ACE, angiotensinogen (AGT) and angiotensin II receptor type I (AGTR1) polymorphisms with diabetic nephropathy (DN) in Tunisians. METHODS: The study population comprised 236 type 2 diabetic patients: with nephropathy (DN = 47) and without nephropathy (DM = 189). Genotyping of ACE-I/D-rs1799752, ACE-rs4343G>A, AGT-rs5050A>C, AGT-rs 4762C>T, AGT-rs699A>G, and AGTR1-rs5186A>C was performed by PCR-RFLP. Haplotype and statistical analysis were realized using SNP Analyzer2.0 and SPSS20, respectively. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for potential confounding factors (age, gender, diabetes duration, hypertension…), an increased risk for DN was associated with mutated alleles of rs4762 (OR = 10.25, p = 0.001), rs699 (OR = 22.21, p < 0.001), and rs5186 (OR = 11.25, p < 0.001). However, mutated alleles of rs1799752 seemed to be protector (OR = 0.41, p = 0.011). Adjusted ORs of DN associated with the ACE haplotype (DA) was (OR = 9.56, p = 0.047) and with the ACE-AGT haplotype (ATADAA) was (OR = 5.38, p = 0.032). CONCLUSIONS: This study indicates that common variants in ACE, AGT, and AGTR1 seem to play a role in genetic susceptibility to DN in Tunisian population and provides evidence for a disease haplotype: ATADAA.

Correction: Unlocking the power of synergy: High-intensity functional training and early time-restricted eating for transformative changes in body composition and cardiometabolic health in inactive women with obesity.

[This corrects the article DOI: 10.1371/journal.pone.0301369.].

Unlocking the power of synergy: High-intensity functional training and early time-restricted eating for transformative changes in body composition and cardiometabolic health in inactive women with obesity.

OBJECTIVE: The purpose of this study was to examine the long-term effects of time-restricted eating (TRE), with or without high intensity functional training (HIFT), on body composition and cardiometabolic biomarkers among inactive women with obesity. METHODS: Sixty-four women (BMI = 35.03 ± 3.8 kg/m2; age = 32.1 ± 10 years) were randomly allocated to either: (1) TRE (≤8-h daily eating window, with ad libitum energy intake) group; (2) HIFT (3 sessions/week) group; or (3) TRE combined with HIFT (TRE-HIFT) group. The interventions lasted 12 weeks with a pre-post measurement design. A HIFT session consists of 8 sets of multiple functional exercises with self-selected intensity (20 or 30s work/10s rest). RESULTS: TRE-HIFT showed a greater decrease of waist and hip circumferences and fat mass compared to TRE (p = 0.02, p = 0.02 and p<0.01; respectively) and HIFT (p = 0.012, p = 0.028 and p<0.001; respectively). Weight and BMI decreased in TRE-HIFT compared to HIFT group (p<0.001; for both). Fat-free mass was lower in TRE compared to both HIFT and TRE-HIFT groups (p<0.01 and p<0.001; respectively). Total cholesterol, triglyceride, insulin, and HOMA-IR decreased in TRE-HIFT compared to both TRE (p<0.001, p<0.01, p = 0.015 and p<0.01; respectively) and HIFT (p<0.001, p = 0.02, p<0.01 and p<0.001; respectively) groups. Glucose level decreased in TRE-HIFT compared to HIFT (p<0.01). Systolic blood pressure decreased significantly in both TRE-HIFT and HIFT groups compared to TRE group (p = 0.04 and p = 0.02; respectively). CONCLUSION: In inactive women with obesity, combining TRE with HIFT can be a good strategy to induce superior effects on body composition, lipid profile and glucose regulation compared with either diet or exercise intervention alone. TRIAL REGISTRATION: Clinical Trials Number: PACTR202301674821174.

Fenugreek seeds, a hepatoprotector forage crop against chronic AlCl3 toxicity.

BACKGROUND: Having considered how bioavailable aluminium (Al) may affect ecological systems and animals living there, especially cattle, and in search for a preventive dietary treatment against Al toxicity, we aimed to test the protective role of fenugreek seeds against chronic liver injury induced by aluminum chloride (AlCl3) in Wistar rats. RESULTS: Five months of AlCl3 oral exposure (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) caused liver atrophy, an inhibition of aspartate transaminase (AST), alanine transaminase (ALT) and glutamyl transpeptidase (GGT), an enhancement of both lipid peroxidation and lactate dehydrogenase (LDH) activity and an increase of total protein level in liver. Moreover, histopathological and histochemical examinations revealed moderate alterations in the hepatic parenchyma in addition to a disrupted iron metabolism. Co-administration of fenugreek seed powder (FSP) at 5% in pellet diet during two months succeeded to antagonize the harmful effects of AlCl3 by restoring all tested parameters. CONCLUSION: This study highlighted the hepatotoxicity of AlCl3 through biochemical and histological parameters in one hand and the hepatoprotective role of fenugreek seeds on the other hand. Thus this work could be a pilot study which will encourage farmers to use fenugreek seeds as a detoxifying diet supplement for domestic animals.

In vitro effects of three antidepressant drugs on plasma paraoxonase activity.

BACKGROUND: Paraoxonase 1 (PON1) is important in organophosphates and xenobiotic metabolism and as an antioxidant bio-scavenger. PON1 activity was shown to significantly decrease in depressed patients after antidepressant treatment instauration. Our aim was to investigate the in vitro inhibitory effects of three antidepressants (imipramine, amitriptyline and fluoxetine) on PON1 activity. METHODS: Plasma from healthy volunteers was spiked with antidepressant drugs. The working solutions were then diluted with plasma to obtain concentrations that covered the therapeutic margin. PON1 was tested by a kinetic method in triplicate after incubation at 37°C for 2 h. RESULTS: Tricyclic antidepressants significantly inhibited PON1. Fluoxetine had no effect. The inhibition percentage for imipramine was 15.6% at 100 µg/L after incubation for 1 h (131±1 vs. 155±2 IU/L; p<0.01). At 350 µg/L, the inhibition percentage for imipramine 19.2% after 1 h and 20.2% after 2 h. Amitriptyline was a stronger inhibitor: 26% after 30 min at 125 µg/L. At 250 µg/L, the inhibition percentage for amitriptyline was 36.5% after 30 min (100±4 vs. 159±2 IU/L; p<0.01). CONCLUSIONS: The tested tricyclic antidepressants significantly inhibit PON1 activity in a concentration-dependent manner. Amitriptyline had a higher inhibition potency than imipramine.

[Pseudocholinesterase activity in type 1 bipolar patients]. / Étude de l'activité pseudocholinestérasique chez des patients bipolaires de type 1.

This study aims to investigate the variation of pseudocholinesterase activity (BuChE) in bipolar patients and to explore its relation to the clinical and therapeutic characteristics of this disease. Our study included 105 patients with bipolar disorder and 100 control subjects aged 38.7 ±â€Š12.2 and 36.4 ±â€Š15.7 y, respectively. BuChE was determined by kinetic methods on Cobas Integra 400 plus™. Compared with controls, patients had a significantly higher pseudocholinesterase activity. Moreover, this increase was significantly associated (p = 0.001) with bipolar disorder with sensibility of 58% and specificity of 62% at threshold of 7392 IU/L. There was no significant change in pseudocholinesterase activity in relation to illness episodes and treatment, whereas the lowest values of this activity were seen in euthymic patients and those taking psychotics. Therefore, this activity is a real interest in the biological monitoring of patients as a risk factor for neurodegenerative diseases associated with bipolar disorder. But it would be most useful to evaluate their interest as a predictor of bipolar disorder in patients at risk.

[Evaluation of the renal function in type 2 diabetes: clearance calculation or cystatin C?]. / Évaluation de la fonction rénale chez le diabétique de type 2 : calcul des clairances ou cystatine C ?

Screening for diabetic nephropathy is usually done by albuminuria/24h and the use of creatinine clearance. The objective of this study was to evaluate the renal function in Type 2 diabetes by using different formulas of creatinine clearance and to assess the contribution of cystatin C; 83 adults with type 2 diabetes (23 men and 60 women) and 83 adult controls (40 men and 43 women) were studied. Biochemical parameters were determinated on Coba 6000™ (Roche diagnostics). Diabetics showed a significant increase in blood glucose, cholesterol, triglycerides, LDLc, the ApoB, Lp(a), urea, uric acid, creatinine and cystatin C and lower HDLc. Cystatin was increased in patients with degenerative complications and in hypertensive patients. We found strong correlations of cystatin C with creatinine (r = 0.9454), urea (r = 0.8999) and uric acid (r = 0.8325). We found a significant exponentially increase of creatinine and cystatin C from one stage to another. Cystatin C has a strong association with MDRD (r = 0.8086) and CG (r = 0.7915) and a low one with creatinine clearance (r = 0.1044). In conclusion, the use of cystatin C for screening and early treatment of incipient diabetic nephropathy appears to be adequate. CG and MDRD formulas still hold their place, in regards to the classical determination of creatinine clearance, to monitor patients.

[Risk of hyperthyroidism in a Tunisian population of smokers]. / Risque d'hyperthyroïdie dans une population de fumeurs tunisiens.

OBJECTIVES: This study aimed to examine the effect of cigarette smoking on thyroid function especially TSH and FT4 levels and to determine the correlation between these parameters and the biological tobacco markers: plasma thiocyanate and cotininuria. METHODS: The initial study was conducted on 300 voluntary subjects, 162 current smokers, 27 former smokers and 111 nonsmokers aged respectively 35.4±16.1, 31.6±1.8 and 38.0±14.6 years. TSH and FT4 levels were determined using electrochemiluminescence, cotinine by homogenous enzymes immunoassay and thiocyanate by selective electrode. RESULTS: Before and after adjustment for potentials confounder factors, we found a significant decrease of TSH and a significant increase of FT4 levels according to smoking status. In current and former smokers, we found significant decrease in TSH and increase in FT4 levels compared to nonsmokers. Moreover, we noted a significant decrease of TSH levels in subjects smoking more than 40 cigarettes/day compared to those smoking less than 20 cigarettes/day. Additionally, TSH levels were significantly reduced in subjects smoking more than 5 years compared to those who smoked < 5 years. In smokers, cotininuria and plasma thiocyanates presented a negative correlation with TSH and a positive correlation with FT4 levels. CONCLUSION: cigarette smoking is associated to perturbations in FT4 and TSH levels, these perturbations were strongly correlated with smoking status parameters. The associations with smoking cessation suggest that smoking may have reversible effects on thyroid function. Therefore, it is recommended to stop or reduce smoking and to introduce testing of thyroid estimation as a routine test, especially in subjects at risk.

Effect of cigarette smoking on paraoxonase 1 activity according to PON1 L55M and PON1 Q192R gene polymorphisms.

OBJECTIVE: This study aims to investigate the effect of cigarette smoking on paraoxonase 1 (PON1) activity according to PON1 L55M and PON1 Q192R gene polymorphisms. MATERIALS AND METHODS: Our sample included 300 voluntary subjects: 138 nonsmokers and 162 current smokers aged 38.47 ± 21.91 and 35.55 ± 16.03 years, respectively. PON1 activity was determined by kinetic methods. L55M and Q192R gene polymorphisms of PON1 were determined by multiplex polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). RESULTS: We found in smokers a significant decrease of PON1 activity before and after adjustment. We noted a significant association between smoking status and lower PON1 activity [odds ratio (OR) = 3.03, confidence interval 95% = 1.5-5.9, p = 0.001]. In smokers, there was significant association between PON1 activity and PON1 L55M polymorphisms (p = 0.01). Also, the 55MM genotype presented the lowest paraoxonase activity, while the 55LL genotype showed the highest one. After adjustment for confounding variables, smokers with PON1 L55M polymorphism had the highest risk for lower PON1 activity; however, PON1 Q192R genotype might protect smokers from decrease in PON1 activity. We found significant interaction between the effect of cigarette smoking and both PON1 L55M and PON1 Q192R polymorphisms on lower PON1 activity. CONCLUSIONS: Cigarette smoking was significantly associated with decrease in PON1 activity. Moreover, PON1 L55M polymorphism predisposes smokers to decreased PON1 activity in contrast to PON1 Q192R genotype.

Allergie aux protéines du lait de vache chez un nourrisson sous allaitement maternel exclusif.

INTRODUCTION: L'allergie aux protéines du lait de vache (APLV) est l'allergie alimentaire la plus fréquente au cours des premières années de vie. Elle est souvent associée à l'introduction des préparations à base de lait de vache et constitue une maladie rare chez les nourrissons allaités. OBJECTIF: Rapporter le cas d'une APLV chez un nourrisson sous allaitement maternel exclusif. Observation médicale. Un nourrisson âgé de 3 mois a été reçu avec une histoire de diarrhée chronique. La mère nie toute introduction de lait artificiel et le nourrisson est exclusivement nourri au sein. La concentration d'anticorps IgE spécifiques du lait de vache était en faveur de l'APLV. En interrogeant à nouveau la mère, elle souligne la notion de consommation d'une grande quantité de produits laitiers. Leur éviction était associée à un développement normal du nourrisson sans problèmes intestinaux. CONCLUSION: L'APLV peut se développer chez les nourrissons exclusivement allaités au sein. Exclure le lait de vache de l'alimentation de la mère est le seul remède quand elle veut encore allaiter.

Acromegaly: an endocrine pathology with serious consequences / L'acromégalie : une pathologie endocrinienne à lourdes conséquences

Acromegaly is a rare endocrine disorder leading to an acquired physical disfigurement and multisystem damage. It is caused in over 95% of cases by a secreting pituitary adenoma. Latency period between disease onset and diagnosis is mainly 10 years due to progressive chronic evolution and exposure to high levels of GH and IGF-1. Here we present a case of acromegaly with over 25 years of diagnostic delay in 69-years-old male with typical features and recurrent urolithiasis. Biochemical diagnosis was confirmed by high levels of IGF-1and lack of suppression of GH during an oral glucose load. Imaging and histological study revealed a co-secreting GH/ prolactine macroadenoma. After three months of complete transphenoidal surgical resection, biochemical remission was not obtained and the patient was treated by a somatostatin receptor ligand. Based on this severe case with atypical manifestations, the diagnosis of acromegaly should be always considered.

L'acromégalie est une maladie endocrinienne rare caractérisée par un syndrome dysmorphique acquis et des atteintes multi-systémiques invalidantes en rapport, dans 95 % des cas, avec un macroadénome hypophysaire. La lente progression et l'exposition chronique aux fortes concentrations de l'hormone de croissance (Growth Hormone : GH) et de l'Insuline Growth Factor-1 (IGF-1) expliquent le retard du diagnostic de 10 ans en moyenne. Nous rapportons le cas d'une acromégalie chez un sujet âgé de 69 ans diagnostiqué après plus de 25 ans d'installation du syndrome dysmorphique et de lithiases urinaires récidivantes. Le diagnostic a été confirmé biologiquement par des concentrations très élevées et non freinables de GH et par la présence d'un macroadénome hypophysaire exprimant doublement la GH et la prolactine. Après résection chirurgicale complète, l'évaluation biologique n'a pas objectivé de rémission, d'où le recours à un traitement adjuvant par un analogue de la somatostatine. En présence de multiples atteintes atypiques et sévères comme chez ce patient, le diagnostic d'acromégalie doit toujours être évoqué.

Investigation of the Relationship among Cortisol, Pro-inflammatory Cytokines, and the Degradation of Tryptophan into Kynurenine in Patients with Major Depression and Suicidal Behavior.

BACKGROUND: The increased degradation of tryptophan (Trp) along the kynurenine (Kyn) pathway due to inflammation and/or activation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported among the biological factors involved in the pathophysiology of major depressive disorder (MDD) and suicide. However, the interaction among these multiple factors is not yet completely clarified. METHODS: We studied plasma levels of Trp, Kyn, cortisol and proinflammatory cytokines (IL-1, IL- 6, IL-12, IL-20) and calculated the ratio Kyn/Trp as an index of the breakdown of Trp into Kyn in 31 suicidal MDD patients and 67 non-suicidal MDD patients. RESULT: We confirmed that suicidal MDD patients have reduced plasma Trp, higher Kyn and Kyn/Trp ratio, and no difference in cortisol levels than non-suicidal MDD patients. IL-1 and IL-12 levels were significantly higher in suicidal MDD than in non-suicidal MDD (p=0.034 and p=0.023, respectively), whereas Il-6 and IL-20 levels were equal in the two groups. The Kyn/Trp ratio was positively correlated with a pro-inflammatory cytokines index (r=0.309, p=0.002) and cortisol (r=0.368, p=0.001). Notably, the variance in the Kyn/Trp ratio explained by the model including both cortisol and inflammatory parameters as dependent variables, substantially improved compared with the models in which the two parameters were considered separately. CONCLUSION: These findings show that both cortisol and proinflammatory cytokines are involved in the enhanced breakdown of Trp into Kyn occurring in suicidal MDD patients, thus adding new knowledge on the biological mechanisms leading to the activation of the Kyn pathway in MDD and suicide.

Effect of cigarette smoking on plasma homocysteine concentrations.

BACKGROUND: Cigarette smoking has been recognized as a major risk factor for cardiovascular disease, while the role of homocysteine is still not clear. This study investigated the effects of smoking on plasma homocysteine concentration and determined the correlation between this parameter and biological markers of tobacco use, such as plasma thiocyanate and urine cotinine. METHODS: Folate, vitamin B12 and homocysteine were measured in 300 subjects: 138 non-smokers and 162 smokers using immunoassay methods. Cotinine was measured using an enzymatic colorimetric method and thiocyanate by a selective electrode. RESULTS: In smokers, we found a significant increase in homocysteine and a decrease in folate and vitamin B12 levels compared to non-smokers. Homocysteine was strongly correlated with the duration of use and the number of cigarettes consumed. Folate and vitamin B12 were significantly reduced in subjects smoking for more than 20 years compared to those who smoked less than 5 years. Among smokers, we noted a positive correlation between homocysteine and both plasma thiocyanates and cotininuria, and a negative-correlation between cotininuria and plasma folate. CONCLUSIONS: Cigarette smoking increases homocysteine, which is strongly correlated with cotininuria and plasma thiocyanates. Moreover, smokers had tendency to develop hypofolatemia and hypovitamin B12, particularly when the duration of consumption exceeded 20 years.

Hyperhomocysteinemia in Tunisian bipolar I patients.

AIMS: The aim of the present study was to investigate hyperhomocysteinemia in Tunisian bipolar I patients according to 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. METHODS: The subjects consisted of 92 patients with bipolar I disorder diagnosed according to DSM-IV, and 170 controls. Plasma total homocysteine, folate and vitamin B12 were measured. MTHFR C677T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Compared with controls, patients had a significantly higher homocysteine level (16.4 ± 9.8 vs 9.6 ± 4.5 µmol/L; P < 0.001) and a significantly lower folate level (3.2 ± 0.9 vs 6.5 ± 3.2 µg/L; P < 0.001). C677T MTHFR polymorphism genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for MTHFR C677T genotypes, hypofolatemia, hypovitamin B12 and for potential confounding factors, the odds ratio (OR) of hyperhomocysteinemia associated with bipolar disorder remained significant (OR, 5.53; 95% confidence interval: 1.92-15.86; P = 0.001). In patients, there was no significant change in hyperhomocysteinemia, hypofolatemia and hypovitamin B12 with regard to the clinical and therapeutic characteristics, whereas the highest prevalence of hyperhomocysteinemia was found in depressive patients and when illness duration was >12 years. Hypofolatemia was seen in all patients on lithium and in the majority of patients on carbamazepine, and the highest prevalence of hypovitamin B12 was noted in patients taking carbamazepine. CONCLUSION: Hyperhomocysteinemia was more frequent in bipolar I patients independent of C677T polymorphism. Patients had reduced levels of folate, which modulates homocysteine metabolism. Indeed, this finding indicates that folate supplementation may be appropriate for bipolar patients with hyperhomocysteinemia.