Reduced placental size and increased apoptosis are associated with prenatal nicotine exposure in rats.

OBJECTIVE: Smoking during pregnancy has been linked to a variety of negative embryonic and neonatal consequences. Nicotine is the major constituent of tobacco smoke, which was associated with adverse impacts on histological and functional features of the placenta. This study aims to investigate the potential influence of nicotine exposure on the rat placenta and fetus. MATERIALS AND METHODS: Nicotine was administrated through the drinking water of female pregnant rats. The placental size, as well as the fetal body weight and size, were measured at E20. The mRNA expression of the Bax gene (pro-apoptotic), the Bcl-2 gene (anti-apoptotic) and the angiogenic genes VEGF, Flt-1, and HIF1 were measured in placental tissue. Furthermore, Immunohistochemistry (IHC) using Bax, caspase 9 and VEGF antibodies were performed on placental sections. RESULTS: The results of the current study showed a significant reduction in the size of the placenta along with fetal body weight in nicotine treated group compared to the control group. Apoptosis was observed to be boosted in the placentas of the nicotine-treated group. This was associated with upregulation of Bax expression combined with no change in the expression of Bcl-2 in the treated group. On the other hand, there was no difference in the expression of angiogenic factors VEGF, Flt-1, or HIF1 between tested groups. CONCLUSIONS: In utero nicotine exposure in pregnant rats showed deleterious impacts on fetus growth and weight, as well as placental size. These were accompanied by increased apoptosis within the placenta, as revealed by Bax gene upregulation.

Pharmacogenetic screening of A1555G and C1494T mitochondrial mutations and the use of ototoxic drugs among Jordanians.

OBJECTIVE: Hearing loss may impact an individual's psychosocial behaviors and lead to cognitive decline. The goals of this study were to describe the frequency of nonsyndromic hearing loss (NSHL) among Jordanian patients with regular exposure to ototoxic drugs, perform screening for A1555G and C1494T mitochondrial mutations (12S rRNA gene) and identify predictors of hearing loss. MATERIALS AND METHODS: A cross-sectional study was conducted in which medical records were reviewed to record the pattern of ototoxic drug use among participants. The pure tone audiometry (PTA) test was used to assess hearing performance. Direct sequencing was performed following PCR amplification to screen for mitochondrial mutations of interest. RESULTS: One hundred sixty-two patients reported regular use of ototoxic drug(s); sixty-five percent of them suffered from NSHL, mostly of mild-moderate severity. No A1555G or C1494T mutation was detected in any participant. Aspirin (82%) was the most commonly used ototoxic drug, followed by loop diuretics (77%) and aminoglycosides (57%). Advanced age, more comorbidities and more ototoxic drugs taken increased the likelihood of hearing loss (p<0.01). CONCLUSIONS: Hearing loss is prevalent among Jordanian patients treated with ototoxic drugs. Early intervention and management services for this population remain critical needs.

Nigella sativa oil and thymoquinone ameliorate albuminuria and renal extracellular matrix accumulation in the experimental diabetic rats.

OBJECTIVE: Increasing evidence suggests that Nigella sativa oil (NSO) and its principal bioactive constituents, thymoquinone (TQ), exhibit antioxidant, antihyperglycemic and renoprotective effects in streptozotocin (STZ)-induced diabetes in rats. However, the potential molecular mechanisms by which NSO and TQ may exert their actions in the diabetic kidney are still poorly characterized. This study was designed to investigate the effect of NSO and TQ treatment on the albuminuria, podocyte injury and the complex systems controlling the extracellular matrix proteins accumulation and angiogenesis in the STZ-induced model of diabetic nephropathy. MATERIALS AND METHODS: Adult female Wistar rats were divided into four experimental groups (control, untreated STZ-diabetic, and NSO or TQ treated STZ-diabetic rats). The treated rats received 2 mL/kg NSO or 50 mg/kg TQ via oral gavage once a day for 10 weeks. RESULTS: The results showed that the albuminuria and the kidney weight/body weight ratio were increased in the diabetic rats compared with the control animals and they were significantly ameliorated by the treatment with NSO or TQ. The real-time PCR showed that the NSO and TQ treatment prevented diabetes-induced downregulation of mRNA expression of the podocyte-specific marker (podocin) as well as the mRNA overexpressions of collagen IV, transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor-A (VEGF-A) in the diabetic kidney. These results were also confirmed by immunohistochemistry. CONCLUSIONS: NSO and TQ treatment decreased albuminuria in the experimental models of the diabetic nephropathy by the preservation of the podocyte function; along with the suppression of enhanced extracellular matrix gene expression through interfering with TGF-ß1 production and angiogenesis.

Cardiac autonomic dysfunction in young obese males is not associated with disturbances in pituitary-thyroid axis hormones.

OBJECTIVE: Obesity has been associated with hypothyroidism and cardiac autonomic dysfunction. The present study aimed to investigate whether cardiac autonomic dysfunction in young obese males might be related to an underlying thyroid disturbance. PATIENTS AND METHODS: On the basis of body mass index (BMI), 40 participants were grouped into normal weight group (NW; BMI = 18.5-25 kg/m(2); n = 15), over weight group (OW; BMI = 25-29.9 kg/m(2); n = 12) and obese group (OB; BMI ≥ 30 kg/m(2); n = 13). Electrocardiogram was recorded using PowerLab system and the time and frequency domain measures of heart rate variability (HRV) were calculated. Fasting blood samples were drawn for measurement of serum thyroid stimulating hormone (TSH), total thyroxin (TT4) and total triiodothyronine (TT3) concentrations. RESULTS: The levels of TSH, TT4 and TT3 were not significantly different between the groups. The frequency domain HRV parameter reflecting parasympathetic tone (high-frequency normalized units, HFnu) was significantly reduced in OB group. The parameters which reflect sympathetic activation (Heart rate, low-frequency normalized units; LFnu and the LF/HF ratio) were significantly increased in the OB group. HFnu was significantly and negatively correlated with BMI, waist hip ratio and body fat percentage, whereas LFnu and LF/HF ratio were significantly and positively correlated with the above mentioned parameters. No significant relationships were noted between the HRV parameters and the levels of TSH or thyroid hormones. CONCLUSIONS: Cardiac autonomic dysfunction in obese young adult males is not linked with underlying thyroid disturbance.

Anti-C1q antibodies and systemic lupus erythematosus in the Tunisian population.

OBJECTIVES: The presence of a wide variety of autoantibodies is a characteristic feature of systemic lupus erythematosus (SLE). Although non-specific, anti-complement C1q (anti-C1q) were shown to correlate with the occurrence of active nephritis. The present study aimed to investigate the prevalence of anti-C1q in Tunisian SLE patients and their association with clinical manifestations, especially renal involvement. PATIENTS AND METHODS: IgG anti-C1q antibodies were assessed by Elisa in 98 SLE patients, 55 patients with rheumatoid arthritis (RA) and 65 healthy individuals (HI). RESULTS: Anti-C1q were found in 53 (54.1%) patients with SLE, three (5%) patients with RA and six (9.3%) HI. Among the 65 patients with renal involvement, anti-C1q were present in 35 (53.8%) patients. There was no significant association between anti-C1q and renal or extrarenal manifestations. In addition, there was no correlation between anti-C1q titer and SLEDAI index. Anti-C1q were significantly associated with anti-nucleosome (P=0.001), anti-Sm (P=0.01) and a low C4 level (P=0.046). Concomitant presence of anti-C1q and anti-dsDNA antibodies was not associated with renal manifestations. CONCLUSION: Our study shows that prevalence of anti-C1q was comparable with that previously reported in Caucasian populations. These antibodies were associated with a low C4 level. However, there was no association between anti-C1q and renal involvement or severity of nephritis.

Activity of hepatic but not skeletal muscle carnitine palmitoyltransferase enzyme is depressed by intravenous glucose infusions in lactating dairy cows.

A positive energy balance in dairy cows pre-partum may decrease hepatic carnitine palmitoyltransferase (CPT) enzyme activity, which might contribute to disturbances of lipid metabolism post-partum. The purpose of this study was to investigate whether skeletal muscle CPT activity can also be downregulated during positive energy balance. Mid-lactating dairy cows were maintained on intravenous infusion of either saline (control) or glucose solutions that increased linearly over 24 days, remained at the 24-day level until day 28 and were suspended thereafter. Liver and skeletal muscle biopsies, as well as four diurnal blood samples, were taken on days 0, 8, 16, 24, and 32, representing infusion levels equivalent to 0%, 10%, 20%, 30% and 0% of the net energy for lactation (NE(L)) requirement respectively. Glucose infusion increased serum insulin concentrations on day 16 and 24 while plasma glucose levels were increased at only a single time point on day 24. Serum beta-hydroxybutyric acid concentrations decreased between day 8 and 24; whereas changes in non-esterified fatty acids were mostly insignificant. Total lipid contents of liver and skeletal muscle were not affected by treatment. Hepatic CPT activity decreased with glucose infusion (by 35% on day 24) and remained decreased on day 32. Hepatic expression levels of CPT-1A and CPT-2 mRNA were not significantly altered but tended to reflect the changes in enzyme activity. In contrast to the liver, no effect of glucose infusion was observed on skeletal muscle CPT activity. We conclude that suppression of CPT activity by positive energy balance appears to be specific for the liver in mid-lactating dairy cows.

Expression and activity of key hepatic gluconeogenesis enzymes in response to increasing intravenous infusions of glucose in dairy cows.

The present study aimed at investigating whether increasing concentrations of glucose supply have a depressive effect on the mRNA abundance and activity of key gluconeogenic enzymes in dairy cows. Twelve Holstein-Friesian dairy cows in mid-lactation were intravenously infused with saline (SI; n = 6) or a 40% glucose solution (GI; n = 6). For GI cows, the infusion dose increased by 1.25%/d relative to the initial NE(l) requirement until a maximum dose equating to surplus 30% NE(l) was reached on d 24. Cows receiving SI received an equivalent volume of 0.9% saline solution. Blood samples were taken every 2 d, and liver biopsies were collected every 8 d. A treatment x quadratic dose interaction (P < 0.01) was observed for the concentration of plasma glucose and serum insulin. The interactions were due to positive quadratic responses of the concentrations of glucose and insulin for GI cows, whereas the concentrations of glucose and insulin did not change over time for SI cows. The concentration of beta-hydroxybutyric acid (BHBA) and serum urea nitrogen (BUN) responded in a treatment x quadratic dose manner, such that greater decreases (P < 0.01) in BHBA and BUN concentrations were observed for cows receiving GI than SI as the dosage increased. Serum NEFA concentration tended to follow a similar pattern as serum BHBA and BUN; however, the interaction was not significant (P = 0.07). The mRNA abundance of gluconeogenesis enzymes followed a linear treatment x dose interaction (P < 0.05) for only pyruvate carboxylase (PC), which was paralleled by a trend for a linear treatment x dose interaction (P = 0.13) for PC enzyme activity. The least PC expression and activity were observed at the largest glucose dosage. The activity, but not mRNA abundance, of fructose 1,6-bisphosphatase (FBPase) showed treatment x quadratic dose interactions (P < 0.05) with decreasing activity at increasing glucose dose. Activities and expression of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase were not affected (P > 0.25) by treatment. In conclusion, hepatic gluconeogenic enzymes are only moderately affected by slowly increasing glucose supply, including a translational or posttranslational downregulation of FBPase activity and a decrease in the mRNA abundance of PC with possible consequences for PC enzyme activity.

Increasing intravenous infusions of glucose improve body condition but not lactation performance in midlactation dairy cows.

The present study was intended to test whether intravenously applied glucose would elicit dose effects on lactation performance similar to those observed after gastrointestinal glucose application. Six midlactation cows received intravenous glucose infusions (GI), increasing by 1.25% of the calculated net energy for lactation (NE(L)) requirement per day, whereas control cows received volume-equivalent saline infusions (SI). Measurements and samples were taken at surplus glucose dose levels of 0, 10, 20, and 30% of the NE(L) requirement, respectively. Body weight and backfat thickness increased linearly with increasing glucose dose for cows on GI compared with SI. No differences were observed in daily feed intake, milk energy output, and energy-corrected milk yield between treatments. However, milk protein percentage and yield increased linearly with the dose of glucose infused in the GI group. Although milk lactose was not affected by treatment during the infusion period, milk lactose percentage and yield decreased for GI, but not SI, once infusions ceased. Based on 5 diurnal blood samples, daily mean and maximum concentrations of plasma glucose and serum insulin showed linear increases with increasing GI, whereas their daily minimum concentrations were unaffected. At GI of 30% of the NE(L) requirement, marked hyperglycemia and hyperinsulinemia were observed at 1600 h (i.e., 1 h postprandially), coinciding with glucosuria. The revised quantitative insulin-sensitivity check index indicated linear development of insulin resistance for the GI treatment but no such change in SI cows. Glucose infusion decreased daily mean and maximum serum beta-hydroxybutyrate and daily minimum nonesterified fatty acid concentrations relative to SI, whereas serum urea nitrogen was only numerically decreased by GI. No changes were observed in the serum activities of gamma-glutamyl transferase and aspartate transaminase and in the serum concentrations of bilirubin and macrominerals. However, serum phosphorus concentration increased after withdrawal of GI, but not SI. Only in GI cows did glycogen content increase or tend to increase linearly in the liver and skeletal muscle. In conclusion, midlactation dairy cows on an energy-balanced diet directed intravenously infused glucose predominantly to body fat reserves rather than increasing lactation performance. This may suggest that the metabolic fate of glucose is modified by metabolic signals, hormonal signals, or both from the portal-drained viscera when absorbed from the intestine.