Curcumin and nano-curcumin mitigate copper neurotoxicity by modulating oxidative stress, inflammation, and akt/gsk-3β signaling

Copper (Cu) is essential for multiple biochemical processes, and copper sulphate (CuSO4) is a pesticide used for repelling pests. Accidental or intentional intoxication can induce multiorgan toxicity and could be fatal. Curcumin (CUR) is a potent antioxidant, but its poor systemic bioavailability is the main drawback in its therapeutic uses. This study investigated the protective effect of CUR and N-CUR on CuSO4-induced cerebral oxidative stress, inflammation, and apoptosis in rats, pointing to the possible involvement of Akt/GSK-3β. Rats received 100 mg/kg CuSO4 and were concurrently treated with CUR or N-CUR for 7 days. Cu-administered rats exhibited a remarkable increase in cerebral malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 associated with decreased GSH, SOD, and catalase. Cu provoked DNA fragmentation, upregulated BAX, caspase-3, and p53, and decreased BCL-2 in the brain of rats. N-CUR and CUR ameliorated MDA, NF-κB p65, and pro-inflammatory cytokines, downregulated pro-apoptotic genes, upregulated BCL-2, and enhanced antioxidants and DNA integrity. In addition, both N-CUR and CUR increased AKT Ser473 and GSK-3β Ser9 phosphorylation in the brain of Cu-administered rats. In conclusion, N-CUR and CUR prevent Cu neurotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis and upregulating AKT/GSK-3β signaling. The neuroprotective effect of N-CUR was more potent than CUR

Prevention of Vitamin D deficiency in infancy: daily 400 IU vitamin D is sufficient

<p>Summary</p> <p>Aim-objective</p> <p>Vitamin D deficiency and rickets in developing countries continues to be a major health problem. Additionally, the increase of cases of rickets in children of some ethnic groups in the United States and European countries has provided this issue to be updated. Obviously, powerful strategies are necessary to prevent vitamin D deficiency nation-wide. In 2005, a nationwide prevention program for vitamin D deficiency was initiated, recommending 400 IU vitamin D per a day.</p> <p>This study was designed to evaluate the efficacy of the prevention program.</p> <p>Methods</p> <p>Eighty-five infants who were recalled as part of the national screening program for congenital hypothyroidism between February 2010 and August 2010 at Kocaeli University Children's Hospital were evaluated in terms of their vitamin D status as well. All babies had been provided with free vitamin D (Cholecalciferol) solution and recommended to receive 400 IU (3 drops) daily. Information regarding the age at start of supplementation, the dosage and compliance were obtained from the mothers with face-to-face interview. Serum 25-hydroxy vitamin D (25-OH-D), alkaline phosphatase (AP), parathormone (PTH) levels were measured.</p> <p>Results</p> <p>The mean age at which Vitamin D3 supplementation began was 16.5 ± 20.7 (3-120) days. Ninety percent of cases (n:76) were receiving 3 drops (400 IU) vitamin D3 per day as recommended; 70% of cases (n:59) were given vitamin D3 regularly, the remainder had imperfect compliance. Among those children who are older than 12 months, only 20% continued vitamin D supplementation. No subject had clinical signs of rickets. The mean 25-OH-D level was 42,5 ± 25,8 (median: 38.3) ng/ml. Ten subjects (12%) had their serum 25-OH-D levels lower than 20 ng/ml (6 between 15-20 ng/ml, 3 between 5-15 ng/ml and only one < 5 ng/ml).</p> <p>Conclusions</p> <p>400 U/day vitamin D seems adequate to prevent vitamin D deficiency. However, we believe that the program for preventing vitamin D deficiency in Turkey, needs to be reinforced to start immediately after birth, and to continue beyond 1 year of age at 400U regular daily dosage.</p

Parents' knowledge and behaviour concerning sunning their babies; a cross-sectional, descriptive study

BACKGROUND: For centuries, sunlight has been used for therapeutic purposes. Parents still sun their infants to treat neonatal jaundice, nappy rash or mostly to supply vitamin D for bone development as a consequence of health beliefs. In this study we aimed to assess knowledge and behaviour of parents about benefits of sunlight and sun protection. METHODS: In this study, parents attending to governmental primary healthcare units for their children's routine vaccinations, upon their informed consent, were consecutively enrolled during one month. Data were collected by a semi-structured questionnaire. RESULTS: The mean age of 118 enrolled parents and their babies were 27.9 ± 6.5 years and 8.3 ± 5.8 months, respectively. Most of the participants were mothers (93.2%), housewives (81.4%) with an educational level of ≥6 years (71.2%). Sunlight was considered beneficial for bone development (86.4%), diaper rash (5.9%) and neonatal jaundice (12.7%). In case of neonatal jaundice 72.0% of the participants reported that they would consult a physician. Most of the participants (82.2%) were sunning their babies outdoors. Nearly half (49.7%) of them got this information from medical staff. Fifty two percent of the parents were sunning their babies before 10–11 a.m. and/or after 3 p.m. Only 13.6% of parents reported using sunscreen for their babies, and the majority of them were using sun protecting factor ≥ 15. One forth of the sunscreen users was using sunscreen according to their physicians' advice. CONCLUSION: Most of the participants were aware of the benefits of sunlight; especially for bone development. However they were displaying inappropriate behaviour while sunning their babies for health reasons. More education should be given to parents about the danger of sunlight at primary health care units while advising to sun their babies, if any

Turner syndrome and associated problems in turkish children: A multicenter study

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosi) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto’s thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan. © Journal of Clinical Research in Pediatric Endocrinology

Adolescents with Type 1 diabetes mellitus experience psychosensorial symptoms during hypoglycaemia

AimTo describe mood and psychosensorial symptoms of hypoglycaemia in adolescents with Type 1 diabetes mellitus in two countries with different cultures, Turkey and the USA.MethodsWe developed a 68-item questionnaire assessing physical, behavioural, mood and psychosensorial symptom frequency and ratings [‘good’, ‘bad’, or ‘both’ (sometimes good, sometimes bad)]. Adolescents with Type 1 diabetes were recruited from paediatric diabetes clinics at the University of North Carolina at Chapel Hill in the USA and Kocaeli University in Turkey. The percentages of participants at each clinic who endorsed individual symptoms, symptom categories and symptom ratings were calculated and compared.ResultsCronbach’s α values were > 0.7 for each real symptom category. No symptom items were excluded from the questionnaire analysis based on item-total correlation results which were all > 0.2. Data were collected from 132 participants (69 from University of North Carolina, 63 from Kocaeli University, 54% male). The mean (sd) age of the participants was 14.9 (1.9) years, HbA1c level was 8.7 (1.8) % and duration of Type 1 diabetes was 5.8 (3.7) years. On average, each physical symptom was experienced by 65.2% of participants, each behavioural symptom by 46.5%, each mood symptom by 42.8%, and each psychosensorial symptom by 48.9%. On average, each physical, behavioral, mood and psychosensorial symptom was rated as ‘good’ or ‘both’ by 23.0, 29.1, 36.9 and 37.2% of participants, respectively. There were no symptom differences between the groups in each country.ConclusionsIn addition to the classic physical symptoms experienced during hypoglycaemia, adolescents with Type 1 diabetes report psychosensorial, mood and behavioral symptoms, and some describe them as positive experiences. Symptom experiences were similar in these two countries with different cultures

Severe vitamin D deficiency in 6 Canadian First Nation formula-fed infants

Background. Rickets was first described in the 17th century and vitamin D deficiency was recognized as the underlying cause in the early 1900s. Despite this long history, vitamin D deficiency remains a significant health concern. Currently, vitamin D supplementation is recommended in Canada for breast fed infants. There are no recommendations for supplementation in formula-fed infants. Objective. The objective of this report is to bring attention to the risk of severe vitamin D deficiency in high risk, formula fed infants. Design. A retrospective chart review was used to create this clinical case series. Results. Severe vitamin D deficiency was diagnosed in six formula-fed infants over a two-and-a-half year period. All six infants presented with seizures and they resided in First Nation communities located at latitude 54 in the province of Manitoba. While these infants had several risk factors for vitamin D deficiency, they were all receiving cow&#x0027;s milk based formula supplemented with 400 IU/L of vitamin D. Conclusion. This report suggests that current practice with regards to vitamin D supplementation may be inadequate, especially for high-risk infants. Health care professionals providing service to infants in a similar situation should be aware of this preventable condition. Hopefully this would contribute to its prevention, diagnosis and management

Laser Vaporization of Mouth Lesions, an Overview

Lasers are utilized in dentistry as a therapeutic tool or as an auxiliary tool. The major purpose of employing lasers in dentistry is to overcome the difficulties that are currently observed in traditional dental treatment treatments. The laser is used in hard tissue applications such as caries prevention, bleaching, restorative removal and curing, cavity preparation, dentinal hypersensitivity, growth modulation, and diagnostics, whereas soft tissue applications include wound healing, removal of hyperplastic tissue to uncover impacted or partially erupted teeth, photodynamic therapy for malignancies, and photo-stimulation of herpetic lesions. Lasers' capacity to perform minimally invasive operations with minimum patient discomfort has proven effective in the patient delivery system in dentistry practice. The availability of lasers with various wavelengths has produced a surgical panacea, and laser technology has replaced traditional surgical techniques in many oral surgical operations

Physiologically-based pharmacokinetic modeling for single and multiple dosing regimens of ceftriaxone in healthy and chronic kidney disease populations: a tool for model-informed precision dosing

Introduction: Ceftriaxone is one of commonly prescribed beta-lactam antibiotics with several label and off-label clinical indications. A high fraction of administered dose of ceftriaxone is excreted renally in an unchanged form, and it may accumulate significantly in patients with impaired renal functions, which may lead to toxicity.Methods: In this study, we employed a physiologically-based pharmacokinetic (PBPK) modeling, as a tool for precision dosing, to predict the biological exposure of ceftriaxone in a virtually-constructed healthy and chronic kidney disease patient populations, with subsequent dosing optimizations. We started developing the model by integrating the physicochemical properties of the drug with biological system information in a PBPK software platform. A PBPK model in an adult healthy population was developed and evaluated visually and numerically with respect to experimental pharmacokinetic data. The model performance was evaluated based on the fold error criteria of the predicted and reported values for different pharmacokinetic parameters. Then, the model was applied to predict drug exposure in CKD patient populations with various degrees of severity.Results: The developed PBPK model was able to precisely describe the pharmacokinetic behavior of ceftriaxone in adult healthy population and in mild, moderate, and severe CKD patient populations. Decreasing the dose by approximately 25% in mild and 50% in moderate to severe renal disease provided a comparable exposure to the healthy population. Based on the simulation of multiple dosing regimens in severe CKD population, it has been found that accumulation of 2 g every 24 h is lower than the accumulation of 1 g every 12 h dosing regimen.Discussion: In this study, the observed concentration time profiles and pharmacokinetic parameters for ceftriaxone were successfully reproduced by the developed PBPK model and it has been shown that PBPK modeling can be used as a tool for precision dosing to suggest treatment regimens in population with renal impairment

The impact of clothing style on bone mineral density among post menopausal women in Morocco: a case-control study

BACKGROUND: The clothing style is an important factor that influences vitamin D production and thus bone mineral density. We performed a case-control study in order to evaluate the effect of veil wearing (concealing clothing) on bone mineral density in Moroccan post menopausal women. METHODS: The cases were osteoporotic women whose disease was assessed by bone mineral density measurement. Each patient was matched with a non osteoporotic woman for age, and body mass index. All our patients were without secondary causes or medications that might affect bone density. The veil was defined as a concealing clothing which covered most of the body including the arms, the legs and the head. This definition is this of the usual Moroccan traditional clothing style. RESULTS: 178 post menopausal osteoporotic patients and 178 controls were studied. The mean age of the cases and the controls was 63.2 years (SD 7) and the mean body mass index was 32.1 (SD 8). The results of crude Odds Ratios analyses indicated that wearing a veil was associated with a high risk of osteoporosis: OR 2.29 (95% CI, 1.38–3.82). Multiparity or a history of familial peripheral osteoporotic fractures had also a significant effect on increasing the osteoporosis risk (ORs: 1.87 (95% CI, 1.05–3.49) and 2.01 (95% CI, 1.20–3.38)). After a multiple regression analysis, wearing the veil and a history of familial osteoporotic fractures remained the both independent factors that increased the osteoporosis risk (ORs: 2.20 (95% CI, 1.22–3.9) and 2.19 (95% CI, 1.12–4.29) respectively). CONCLUSION: our study suggested that in Moroccan post menopausal women, wearing a traditional concealing clothing covering arms, legs and head increased the risk of osteoporosis. Further studies are required to evaluate the clinical impact of the above findings and to clarify the status of vitamin D among veiled women in Morocco

Nano-curcumin prevents copper reproductive toxicity by attenuating oxidative stress and inflammation and improving Nrf2/HO-1 signaling and pituitary-gonadal axis in male rats

Copper is essential for several cellular processes and is an important catalytic factor for many proteins. However, excess copper can provoke oxidative stress and reproductive toxicity. This study evaluated the effect of liposomal nano-curcumin (N-CUR) and CUR on testicular oxidative injury, inflammation, and apoptosis, and altered steroidogenesis and Nrf2/HO-1 signaling induced by copper sulfate (CuSO4). Rats received CuSO4 and N-CUR or CUR via oral gavage for 7 days. CuSO4 induced histopathological changes and altered pituitary-gonadal axis manifested by decreased serum gonadotropins and testosterone. Testicular steroidogenesis genes (StAR, 3β-HSD, CYP17A1, and 17β-HSD) and androgen receptor (AR) were downregulated in rats that received CuSO4. N-CUR and CUR prevented testicular tissue injury, increased circulating FSH, LH, and testosterone, and upregulated testicular steroidogenesis genes and AR. Additionally, N-CUR and CUR decreased testicular MDA, NO, NF-κB, iNOS, TNF-α, Bax, and caspase-3 while enhanced Bcl-2, Nrf2, and the antioxidants GSH, HO-1, SOD, and catalase. In conclusion, N-CUR and CUR prevented CuSO4-induced reproductive toxicity in male rats by suppressing oxidative injury and inflammatory response and boosting steroidogenesis, sex hormones, and Nrf2/HO-1 signaling. N-CUR was more effective in ameliorating tissue injury, oxidative stress, inflammation, and apoptosis and enhancing steroidogenesis and Nrf2/HO-1 than the native form