Hala H. Mosli

Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective

Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight & prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-β (ER-β) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone–induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-β/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation.

A new gender-specific model for skin autofluorescence risk stratification.

Advanced glycation endproducts (AGEs) are believed to play a significant role in the pathophysiology of a variety of diseases including diabetes and cardiovascular diseases. Non-invasive skin autofluorescence (SAF) measurement serves as a proxy for tissue accumulation of AGEs. We assessed reference SAF and skin reflectance (SR) values in a Saudi population (n = 1,999) and evaluated the existing risk stratification scale. The mean SAF of the study cohort was 2.06 (SD = 0.57) arbitrary units (AU), which is considerably higher than the values reported for other populations. We show a previously unreported and significant difference in SAF values between men and women, with median (range) values of 1.77 AU (0.79–4.84 AU) and 2.20 AU (0.75–4.59 AU) respectively (p-value « 0.01). Age, presence of diabetes and BMI were the most influential variables in determining SAF values in men, whilst in female participants, SR was also highly correlated with SAF. Diabetes, hypertension and obesity all showed strong association with SAF, particularly when gender differences were taken into account. We propose an adjusted, gender-specific disease risk stratification scheme for Middle Eastern populations. SAF is a potentially valuable clinical screening tool for cardiovascular risk assessment but risk scores should take gender and ethnicity into consideration for accurate diagnosis.

Kidney stone composition in overweight and obese patients: a preliminary report

Objective To report preliminary information on urinary stone composition in patients who are either overweight or obese with kidney stone disease. Methods A cohort of patients (n = 138) with nephrolithiasis were prospectively followed from January 2011 for 18 months. Of those, 64 (46%) were found to be overweight with body mass index ≥ 25 kg/m2 and 74 (54%) were obese with body mass index ≥ 30 kg/m2. Stone characteristics including size, location, and composition were studied in detail, and patients’ age, weight, height, and gender were all documented. The stone size and location were studied radiologically while semiquantitative stone analysis was carried out using the DiaSys method, which involves titrimetric determination of calcium, colorimetric determination/visual assessment of oxalate, phosphate, magnesium, ammonium, uric acid, and cystine, and qualitative determination of carbonate. Results Eighteen stones were collected from overweight and obese patients. Those obtained were either spontaneously passed (n = 2), fragments passed following shockwave lithotripsy (n = 11), extracted ureteroscopically (n = 2), or extracted by percutaneous nephrolithotomy (n = 3). About 95% of the stones contained calcium oxalate and more than half contained uric acid. Conclusion This report confirms that kidney stones are mainly composed of calcium oxalate and uric acid in overweight and obese patients with nephrolithiasis.

Severe Vitamin D Deficiency A Significant Predictor of Early Hypocalcemia after Total Thyroidectomy

Objective To assess the role of preoperative serum 25 hydroxyvitamin D as predictor of hypocalcemia after total thyroidectomy. Study Design Retrospective cohort study. Setting University teaching hospital. Subjects and Methods All consecutively performed total and completion thyroidectomies from February 2007 to December 2013 were reviewed through a hospital database and patient charts. The relationship between postthyroidectomy laboratory hypocalcemia (serum calcium ≤2 mmol/L), clinical hypocalcemia, and preoperative serum 25 hydroxyvitamin D level was evaluated. Results Two hundred thirteen patients were analyzed. The incidence of postoperative laboratory and clinical hypocalcemia was 19.7% and 17.8%, respectively. The incidence of laboratory and clinical hypocalcemia among severely deficient (<25 nmol/L), deficient (<50 nmol/L), insufficient (<75 nmol/L), and sufficient (≥75 nmol/L) serum 25 hydroxyvitamin D levels was 54% versus 33.9%, 10% versus 18%, 2.9% versus 11.6%, and 3.1% versus 0%, respectively. Multiple logistic regression analysis revealed preoperative severe vitamin D deficiency as a significant independent predictor of postoperative hypocalcemia (odds ratio [OR], 7.3; 95% confidence interval [CI], 2.3-22.9; P = .001). Parathyroid hormone level was also found to be an independent predictor of postoperative hypocalcemia (OR, 0.6; 95% CI, 0.5-0.8; P = .002). Conclusion Postoperative clinical and laboratory hypocalcemia is significantly associated with low levels of serum 25 hydroxyvitamin D. Our findings identify severe vitamin D deficiency (<25 nmol/L) as an independent predictor of postoperative laboratory hypocalcemia. Early identification and management of patients at risk may reduce morbidity and costs.

Increased body mass index is associated with larger renal calculi.

OBJECTIVE To examine the relationship between the body mass index and the size of renal stones in a group of patients with urolithiasis. METHODS One-hundred seventy-three patients with renal stones were enrolled. Body mass index was calculated on the basis of height and weight measurements, and stone size was either measured accurately (143 patients) or estimated by the radiologist or managing urologist (30 patients). Body mass index and stone size were then cross-tabulated and the results were analyzed. RESULTS Patients with a body mass index of ≥ 25 kg/m(2) (overweight or obese) were found to have 29 (16.8%) small, 84 (48.5%) medium, and 25 (14.5%) large stones, whereas patients in the underweight or normal body mass index categories had 7 (9.5%) small, 19 (10.9%) medium, and 9 (10.6%) large stones. Of the study group, 109/173 (63%) were found to be overweight or obese, of whom all had renal stones ≥ 1 cm, ie, medium or large, when measured at the greatest diameter, indicating a tendency to have larger stones with increasing body mass index that was statistically significant (P = .0001). CONCLUSION A clear relationship exists between increased body mass index and renal stone size, with overweight and obese patients having medium and large stones more frequently than patients with underweight or normal body mass index.

The effect of obesity and components of metabolic syndrome on urinary and sexual functions in Saudi men

Objective To establish a possible association between obesity, measured by waist circumference (WC) and body mass index (BMI), and voiding and sexual functions in a random cohort of Saudi men. Materials and methods An outpatient men’s health clinic was set up at King Abdulaziz University Hospital in Jeddah, Saudi Arabia and men were invited to discuss their sexual and urinary functions. The data collected included age, WC, weight, height, blood pressure, history of diabetes, hypertension, and smoking. The International Prostate Symptom Score (IPSS) and the International Inventory of Erectile Function (IIEF-5) questionnaire were used to assess urinary tract symptoms and sexual function, respectively. Serum testosterone, prostate-specific antigen and cholesterol levels were measured and documented. Data were analyzed using the Statistical Package for the Social Sciences. Results We recruited 113 participants. The mean WC and BMI of the men were 104 ± 14.599 cm and 29.706 kg/m2, respectively. Thirty-seven men (32.7%) had an IPSS ≥ 8 points. Sexual disorders were reported in 19 men; 16 men had erectile dysfunction, while three had premature ejaculation. Of the whole cohort, 37 men were diabetic, of which 15 (40.5%) had an IPSS ≥ 8 and 13 (35%) were either overweight or obese. Conclusion Increased WC and BMI were associated with diabetes mellitus and large percentages of voiding and sexual disorders.

Obesity and morbid obesity associated with higher odds of hypoalbuminemia in adults without liver disease or renal failure

Background and objective Studies are needed in order to inform recommendations for interpreting albumin levels among obese individuals without known medical conditions associated with hypoalbuminemia. The objective of this study was to examine the association of obese and morbidly obese status with hypoalbuminemia, while adjusting for age, sex, diabetes, prediabetes, diabetic nephropathy, and nephrotic syndrome. Patients and methods Retrospective data collection from adult patients presenting to the outpatient Endocrinology and Metabolism Clinic was performed between January 2015 and December 2015. An initial sample of 180 patients was selected. After excluding patients who were younger than 18 years, who had known cases of liver disease or renal failure, or who had missing data, a final sample of 122 subjects was identified. Serum albumin and objectively measured weight and height data were retrieved from hospital records. A board-certified endocrinologist reviewed patient records to identify the presence of renal and diabetic conditions. Descriptive statistics were used to examine sample characteristics. Multiple logistic regression analysis was used to examine the association of obesity and morbid obesity with hypoalbuminemia (serum albumin < 34 g/L) while adjusting for age, sex, diabetes, prediabetes, diabetic nephropathy, and nephrotic syndrome. Results Approximately 43% of the sample were categorized as obese and 13% were categorized as morbidly obese. The mean serum albumin level was 38.00 g/L (standard deviation [SD] = 4.26) among subjects who were neither overweight nor obese, 38.35 g/L (SD = 0.48) among overweight subjects, 34.57 g/L (SD = 4.71) among obese subjects, and 33.81 g/L (SD = 3.71) among morbidly obese subjects. Adjusting for age, sex, diabetes, prediabetes, nephrotic syndrome, and diabetic nephropathy, obese subjects had significantly higher odds of hypoalbuminemia (odds ratio [OR]: 4.10, 95% confidence interval [CI]: 1.50–11.27, P-value = 0.006), as did morbidly obese subjects (OR: 6.94, 95% CI: 1.91–25.23, P-value = 0.003). Conclusion The findings suggest that obesity and morbid obesity can be considered as independent predictors of hypoalbuminemia. The findings can be used to inform future studies aiming to better understand the association of obesity and morbid obesity with hypoalbuminemia and to help inform guidelines for clinicians on how to correctly interpret and utilize serum albumin data for obese individuals.

Maternal Gestational Diabetes Associated with Higher Child BMI Z-Score at Preschool and Lower Likelihood of Breastfeeding Initiation

Objectives : To examine the association of maternal GDM with 1) child BMI z-score at preschool; 2) breastfeeding initiation and duration, while adjusting for child birthweight in addition to potential confounders. Method : Sample included 53 children (3 - 5 years old) recruited from two preschools in Jeddah, Saudi Arabia. Mothers completed a self-administered questionnaire. Child anthropometry was completed using standardized procedures. BMI z-scores were calculated using the WHO standards/reference data. Linear regression models were tested to examine the association between maternal GDM and child BMI z-score, as well as breastfeeding duration. Logistic regression models were tested to examine the association between maternal GDM and breastfeeding initiation. Models were adjusted for child birthweight, maternal BMI, and maternal age at pregnancy. Results : Mean child BMI z-score was 1.10 (SD= 1.22). About one quarter (24.5%) of mothers reported being diagnosed with GDM. Mean birthweight of children whose mothers were diagnosed with GDM was 3.10 kg (SD= 0.74). Adjusting for covariates, we found that maternal GDM was associated with increased child BMI z-score (B= 1.04, 95% CI= 0.14 - 1.94, P-value= 0.02), and lower odds of breastfeeding initiation (OR= 0.10, 95% CI= 0.02 – 0.49, P-value= 0.005). Maternal GDM was not associated with breastfeeding duration (B= -4.75, 95% CI: -11.79 – 2.29, P-value= 0.18). Conclusion : Findings suggest that maternal GDM is associated with higher child BMI z-score at preschool and lower likelihood of breastfeeding initiation. Studies are needed in order to identify the underlying mechanisms of associations. Obesity prevention programs may target children whose mothers were diagnosed with GDM; prenatal breastfeeding counseling may be offered.

Corrigendum: A new gender-specific model for skin autofluorescence risk stratification

This corrects the article DOI: 10.1038/srep10198.

Ethnicity and skin autofluorescence-based risk-engines for cardiovascular disease and diabetes mellitus

Skin auto fluorescence (SAF) is used as a proxy for the accumulation of advanced glycation end products (AGEs) and has been proposed to stratify patients into cardiovascular disease (CVD) and diabetes mellitus (DM) risk groups. This study evaluates the effects of seven different ethnicities (Arab, Central-East African, Eastern Mediterranean, European, North African, South Asian and Southeast Asian) and gender on SAF as well as validating SAF assessment as a risk estimation tool for CVD and DM in an Arabian cohort. SAF data from self-reported healthy 2,780 individuals, collated from three independent studies, has been linear modelled using age and gender as a covariate. A cross-study harmonized effect size (Cohens’d) is provided for each ethnicity. Furthermore, new data has been collected from a clinically well-defined patient group of 235 individuals, to evaluate SAF as a clinical tool for DM and CVD-risk estimation in an Arab cohort. In an Arab population, SAF-based CVD and/or DM risk-estimation can be improved by referencing to ethnicity and gender-specific SAF values. Highest SAF values were observed for the North African population, followed by East Mediterranean, Arab, South Asian and European populations. The South Asian population had a slightly steeper slope in SAF values with age compared to other ethnic groups. All ethnic groups except Europeans showed a significant gender effect. When compared with a European group, effect size was highest for Eastern Mediterranean group and lowest for South Asian group. The Central-East African and Southeast Asian ethnicity matched closest to the Arab and Eastern Mediterranean ethnicities, respectively. Ethnic and gender-specific data improves performance in SAF-based CVD and DM risk estimation. The provided harmonized effect size allows a direct comparison of SAF in different ethnicities. For the first time, gender differences in SAF are described for North African and East Mediterranean populations.