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.

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.

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.

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.

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.

Assessment of Pharmacokinetics, Toxicity, and Biodistribution of a High Dose of Titanate Nanotubes Following Intravenous Injection in Mice: A Promising Nanosystem of Medical Interest.

Titanate nanotubes (TiNTs) produced by the static hydrothermal process present a promising nanosystem for nanomedicine. However, the behavior of these nanotubes in vivo is not yet clarified. In this work, for the first time, we investigated the toxicity of these materials, their pharmacokinetic profile, and their biodistribution in mice. A high dose of TiNTs (45 mg/kg) was intravenously injected in mice and monitored from 6 h to 45 days. The histological examination of organs and the analysis of liver and kidney function markers and then the inflammatory response were in agreement with a long-term innocuity of these nanomaterials. The parameters of pharmacokinetics revealed the rapid clarification of TiNTs from the bloodstream after 6 h of the intravenous injection which then mainly accumulated in the liver and spleen, and their degradation and clearance in these tissues were relatively slow (>4 weeks). Interestingly, an important property of these materials is their slow dissolution under the lysosome acid environment, rendering them biodegradable. It is noteworthy that TiNTs were directly eliminated in urine and bile ducts without obvious toxicity in mice. Altogether, all these typical in vivo tests studying the TiNT pharmacokinetics, toxicity, and biodistribution are supporting the use of these biocompatible nanomaterials in the biomedical field, especially as a nanocarrier-based drug delivery system.

Influence of orthodontic appliance type on salivary parameters during treatment.

OBJECTIVES: To evaluate the effect of orthodontic appliances on physicochemical, biochemical, and oxidative stress changes in salivary parameters during treatment. MATERIALS AND METHODS: A cohort study was conducted with 112 healthy patients. Salivary samples were taken at baseline, 1 month, and 9 months after placement of the orthodontic appliances used in treatment. RESULTS: A statistically significant difference was observed in certain examined salivary parameters, including enzymes, electrolytes, and oxidative stress markers. CONCLUSIONS: The use of aligners had a lower prevalence of disturbing salivary parameters. Orthodontist must consider these changes to prevent the occurrence of white spot lesions.

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.

Reduced peripheral availability of tryptophan and increased activation of the kynurenine pathway and cortisol correlate with major depression and suicide.

Objectives: Patients affected by major depression (MDD) are at high risk of suicide. The metabolism of tryptophan (Trp) along the serotonin (5-HT) and kynurenine (Kyn) pathways was found dysfunctional in MDD and in suicide. However, a clear biological framework linking dysfunctions in Trp metabolism via 5-HT and Kyn, cortisol, and the activities of tryptophan and indoleamino 2,3-dioxygenase (TDO, IDO) enzymes has not been yet clarified in MDD with or without suicidal behaviours.Methods: We analysed peripheral markers of Trp via 5-HT and Kyn pathways, Kyn/Trp ratio as a measure of TDO/IDO activities, cortisol, and psychopathology in 73 non-suicidal and 56 suicidal MDD patients, and in 40 healthy controls.Results: Plasma Trp levels were lower and the ratio Kyn/Trp higher in suicidal MDD than in non-suicidal MDD patients and controls. Trp levels and the ratio Kyn/Trp correlated with suicidal ideation, and cortisol with the Kyn/Trp ratio. Finally, Trp levels discriminated controls from non-suicidal and suicidal MDD patients, and also non-suicidal from suicidal MDD patients.Conclusions: Reduced availability of Trp for 5-HT synthesis and increased activation of the Kyn pathway and cortisol correlate with depression and suicide. Low plasma Trp levels may be a biomarker of MDD and suicide in MDD.

Protective potential of Opuntia microdasys flower decoction on fructose-alloxan-induced diabetic rats on kidney and pancreas: chemical and immunohistochemical analyses.

Diabetes is a serious condition that is linked to the development of oxidative stress causing among many other effects, kidney failure and pancreatic disorders. However, traditional plant-based remedies can be considered an alternative to diabetes healing. In this context, this study was oriented towards evaluating the protective effect of the flowers of Opuntia microdasys Lehm. collected in Tunisia at a biochemical and histological level on kidneys and pancreas of a type 2 diabetic rats. Renal and pancreatic toxicities were induced in diabetic male Wistar rats by fructose alloxan. Diabetic rats were treated with an extract obtained from flowers collected at post-flowering stage (OFP) (100 and 200 mg kg-1 bw) and metformin (100 mg kg-1 bw) for 28 days. Oral administration of OFP at 200 mg kg-1 bw showed significant reduction of the uric acid, urea, creatinine, amylase, lipase, and glycated hemoglobin (HbAlc). The levels of SOD, CAT, and GPx were increased, while protein carbonyls and lipid peroxidation TBARS levels were reduced in the kidney and pancreas. The altered kidney and pancreas histology were restored in rats treated with OFP. Thus, the present study demonstrated that OFP has antihyperglycemic activity in fructose-alloxan-induced diabetic rats.

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.

[Clinical and biological study of the 31 cases of gallstones]. / Étude clinique et biologique de 31 cas de lithiase biliaire.

This study reports the clinical and biological signs, as well as the morphological aspect and the chemical composition of the calculus during the biliary stones. The study population consisted of 31 patients with an average age of 49 years (30 women and one man) with biliary lithiasis and who had cholecystectomy. Hepatic colic and epigastralgia were the most evocative clinical signs. The calculus were pigmentary (n=6), cholesterolic and mostly single (n=18), and mixed (n=6) and one infectious multiple lithiasis. Cholesterol was found in 22 calculi (70.96%). We have found a significant increase in liver enzymes and total bilirubin, which is more pronounced in pigmentary lithiasis. Our results showed that most gallstones were composed of cholesterol. These results indicate the influence of diet and chronic hemolysis in calculus formation. More investigation should allow knowing the nutritional and environmental factors influencing gallstones formation in Tunisia, in order to prevent this disease.

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.

Hepatoprotective effect of Opuntia microdasys (Lehm.) Pfeiff flowers against diabetes type II induced in rats.

Opuntia sp. has long been used as a folk medicine to treat hepatitis and diabetes in Sicile (Italy). To extract the polyphenols from the flower of Opuntia microdasys Lehm. at post flowring stage and evaluate the antidiabetic activity in vitro and in vivo. The hepatoprotective activity of Opuntia microdasys aqueous flowers extract at post flowering stage (OFP) has been tested for their antidiabetic activity. On fructose-alloxan induced diabete in rat model, evaluating the inhibitory effects of OFP on some carbohydrate metabolizing enzymes, pancreatic α-amylase and intestinal α-glucosidase activities in vitro. The OFP extract showed inhibitory activity against α-glucosidase (IC50=0.17±0.012mg/ml) and α-amylase (IC50=2.55±0.41mg/ml). The inhibitory potential of OFP extract on these enzymes suggests a positive and probable role of this extract in the management and treatment of diabetes mellitus, particularly, for type 2. Oral administration of the OFP at 200mg/kg to diabetic male rats for 28days demonstrated a significant protective effect by lowering the levels of glucose (123.21±1.38mg/dL) and hepatic marker enzymes (AST, ALT, LDH, γ-GT, BT, PAL, TC, LDL-C, HDL-C and TG). OFP attenuated oxidative stress by decreasing the SOD, CAT, GPX activity and the levels of PC and MDA in the liver and restored the histological architecture of the rat liver. OFP has protective effects on the protection of liver, thereby reducing some of the causes of diabetes in experimental animals.

Dichloroacetic acid-induced testicular toxicity in male rats and the protective effect of date fruit extract.

BACKGROUND: The present study was designed to investigate the protective effect of aqueous date extract (ADE) against the dichloroacetic acid (DCA)-induced testicular injury in rats. METHODS: Forty-eight male Wistar rats were randomly divided into six groups of eight: group I served as the control; group II was given ADE (4 ml/kg) by gavage; groups III and IV received DCA at 0.5 and 2 g/L drinking water, respectively; and groups V and VI received DCA at 0.5 and 2 g/L drinking water, respectively, before ADE administration. The experiment was performed for two months. RESULTS: Results showed that the absolute weights of testes and epididymis were decreased following the DCA administration. The testosterone, FSH and LH levels were also decreased. Severe histopathological changes in testes were observed including degeneration of seminiferous tubules and depletion of germ cells. These changes were associated with alterations of oxidative stress markers. Levels of lipid peroxidation and SOD and CAT activities were increased, while activity of GPx and GSH levels were decreased. Pretreatment with ADE has effectively alleviated the oxidative stress induced by DCA thereby restoring these parameters to normal values. CONCLUSIONS: These results suggest that ADE has a protective effect over DCA-induced oxidative damage in rat testes.

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.

Paraoxonase 1 polymorphisms (L55M and Q192R) as a genetic marker of diabetic nephropathy in youth with type 1 diabetes.

INTRODUCTION: Paraoxonase 1 (PON1) polymorphisms have been largely involved in diabetes complications. The aim of the study is to evaluate the effects of PON1 polymorphisms (L55M and Q192R) on diabetic nephropathy (DN). MATERIAL AND METHODS: The study involved 116 children and adolescents with type 1 diabetes (T1D) and 91 healthy subjects. Albumin excretion rate (AER) was determined by immunoturbidimetry. PON1 activity was measured by a spectrophotometric method, and genotyping of PON1 gene was assessed by multiplex PCR followed by RFLP. RESULTS: PON1 activity was inversely correlated to AER (r = -0.245, p = 0.008). A significant decrease (p = 0.037) in PON1 activity was shown between patients with nephropathy and those without (162 [57-618] vs. 316 [37-788] IU/L, respectively). The distribution of AER was, for L55M polymorphism MM > LM > LL (p = 0.002), and for Q192R polymorphism QQ > QR > RR (p < 0.001). The opposite distribution was noted for PON 1 activity (p < 0.001). LMQQ and MMQQ haplotypes seem to increase AER (p = 0.004, p = 0.003, respectively) and to reduce PON1 activity (p = 0.011, p = 0.052, respectively) in youths with T1D. However, LLRR haplotype seems to have the opposite effect. CONCLUSIONS: This study demonstrated that PON1 polymorphisms L55M and Q192R seem to be genetic markers involved in the development of DN in T1D. (Endokrynol Pol 2017; 68 (1): 35-41).

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.