Hepatoprotective effects of diethylcarbamazine in acute liver damage induced by carbon tetrachloride in rats

This research was carried out to determine a potential role of leukotrienes in the acute hepatotoxicity induced by CC14 in rats. An inhibitor of leukotrienes biosynthesis, diethylcarbamazine (DEC, 25 and 50 mg ·kg-1 ip) exerted hepatoprotective effects, decreasing the activity of alanine aminotransfer-ase in serum and the concentration of liver triglycerides. DEC reduced histological damage of liver evidenced by electron microscopy. The hepatoprotective effects of DEC were dose-dependent. The results favor the role of leukotrienes in CC14 hepatotoxicity.     

D-dimer relates positively with increased blood pressure in black South Africans: The SABPA study

Introduction

Hypertension is highly prevalent in black South Africans in which morbidity and mortality from stroke are on the increase. Elevated blood pressure and haemostatic markers can induce changes in blood rheology and endothelial function which could result in a procoagulant state that increases the risk for cerebrovascular disease. Information about the coagulation and fibrinolytic systems of people from African descent are limited. We therefore, investigated the haemostatic profile and its relationships with blood pressure in black South Africans.

Materials and methods

We measured ambulatory blood pressure and haemostatic markers of 201 black and 208 white school teachers. The haemostatic markers included measurements representing coagulation and fibrinolysis (von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1, fibrin D-dimer and clot lysis time).

Results

Black participants displayed significantly higher blood pressure, von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1 and D-dimer levels and longer clot lysis times (p ≤ 0.001). Single, partial and multiple regression analyses showed that systolic (p ≤ 0.011) and diastolic blood pressure (p = 0.010) correlated positively with D-dimer in black participants, while systolic (p ≤ 0.001) and daytime diastolic blood pressure (p = 0.011) correlated negatively with clot lysis time in white participants.

Conclusion

The black population had a more prothrombotic profile, with higher levels of coagulation markers and inhibited fibrinolysis, than the white study participants. The positive association between blood pressure and elevated D-dimer in the blacks may contribute to the high prevalence of hypertension and related increased cardiovascular and cerebrovascular risk in this group.     

Glycation of fibrinogen in uncontrolled diabetic patients and the effects of glycaemic control on fibrinogen glycation

INTRODUCTION: Evidence exists for a relationship between glycaemic control and macrovascular disease. Non-enzymatic glycation of proteins may explain this relationship in part. We investigated the effect of blood glucose control, under out-patient conditions, on fibrinogen glycation as well as the relationship between glycated fibrinogen and glycaemic control using a new sensitive method for the measurement of glycated fibrinogen. MATERIALS AND METHODS: Blood samples were taken from twenty subjects with uncontrolled Type 2 diabetes (HbA1c>7%) to determine the levels of glycation. The subjects were then treated with insulin in order to control blood glucose. Twenty age and BMI matched non-diabetic subjects were included as a reference group. RESULTS: The subjects with diabetes had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects (7.84 vs 3.89 mol glucose/mol fibrinogen; p<0.001). After control of blood glucose, fibrinogen glycation was reduced significantly in the subjects with diabetes (7.84 to 5.24 mol glucose/mol fibrinogen; p<0.0002). The change in glycation during the intervention correlated significantly with the change in capillary glucose in the diabetic group (r=0.6, p=0.005). Fibrinogen glycation was comparable to HbA1c in predicting glycaemic control (p=0.54). Fibrinogen glycation correlated best with the average fasting capillary glucose of the preceding 5-8 days (r=0.54, p=0.014). CONCLUSION: We conclude that glucose control under out-patient conditions decreases fibrinogen glycation in subjects with Type 2 diabetes and that glycated fibrinogen compares well with HbA1c in its relation to glycaemic control.     

The effect of superior semicircular canal dehiscence on intracochlear sound pressures

Semicircular canal dehiscence (SCD) is a pathological opening in the bony wall of the inner ear that can result in conductive hearing loss. The hearing loss is variable across patients, and the precise mechanism and source of variability are not fully understood. Simultaneous measurements of basal intracochlear sound pressures in scala vestibuli (SV) and scala tympani (ST) enable quantification of the differential pressure across the cochlear partition, the stimulus that excites the cochlear partition. We used intracochlear sound pressure measurements in cadaveric preparations to study the effects of SCD size. Sound-induced pressures in SV and ST, as well as stapes velocity and ear canal pressure were measured simultaneously for various sizes of SCD followed by SCD patching. Our results showed that at low frequencies (<600 Hz), SCD decreased the pressure in both SV and ST, as well as differential pressure, and these effects became more pronounced as dehiscence size was increased. Near 100 Hz, SV decreased by about 10 dB for a 0.5-mm dehiscence and by 20 dB for a 2-mm dehiscence, while ST decreased by about 8 dB for a 0.5-mm dehiscence and by 18 dB for a 2-mm dehiscence. Differential pressure decreased by about 10 dB for a 0.5-mm dehiscence and by about 20 dB for a 2-mm dehiscence at 100 Hz. In some ears, for frequencies above 1 kHz, the smallest pinpoint dehiscence had bigger effects on the differential pressure (10-dB decrease) than larger dehiscences (less than 10-dB decrease), suggesting larger hearing losses in this frequency range. These effects due to SCD were reversible by patching the dehiscence. We also showed that under certain circumstances such as SCD, stapes velocity is not related to how the ear can transduce sound across the cochlear partition because it is not directly related to the differential pressure, emphasizing that certain pathologies cannot be fully assessed by measurements such as stapes velocity.     

The effect of glycaemic control on fibrin network structure of type 2 diabetic subjects

Diabetic subjects have been shown to have altered fibrin network structures. One possible cause may be fibrinogen glycation resulting in altered structure/function properties. We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes. Blood samples were taken from twenty uncontrolled diabetic subjects at baseline to determine the levels of fibrinogen glycation and fibrin network structures. The subjects were then treated with insulin until blood glucose control was achieved before end blood samples were taken. Twenty age- and BMI-matched non-diabetic subjects were included as a reference group. The diabetic subjects had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects (7.84 vs. 3.89 mol glucose / mol fibrinogen; p < 0.001). This was significantly reduced during the intervention (7.84 to 5.24 mol glucose / mol fibrinogen; p < 0.0002) in the diabetic group. Both groups had high mean fibrinogen concentrations (4.25 and 4.02 g/l, diabetic and non-diabetic subjects respectively). There was no difference in fibrinogen concentration, porosity, compaction and kinetics of clot formation between the diabetic subjects and non-diabetic subjects at baseline, nor were there any changes during the intervention despite the reduced fibrinogen glycation. Fibrin network characteristics correlated well with fibrinogen but not with any markers of glycaemic control. Improved glycaemic control resulted in decreased fibrinogen glycation but not fibrinogen concentration. It seems as though porosity, compaction and kinetics of clot formation are more related to fibrinogen concentration than fibrinogen glycation in this model.     

The additional cancer yield of clinical breast examination in screening of women at hereditary increased risk of breast cancer: a systematic review

Women at hereditary increased risk of breast cancer are subjected to frequent clinical breast examination (CBE) and radiological evaluation of the breasts. This review appraises the additional cancer yield by CBE in screening of women at increased risk of breast cancer who are also subjected to frequent radiological evaluation. A literature search was conducted to identify all prospective studies on the additional value of CBE in screening of women at increased risk of breast cancer. Quality appraisal of included studies was performed using the QUADAS-2 tool. A total of 514 citations were identified. Relevant literature was scarce and highly heterogeneous. Seven prospective studies were included for review of which two studies reported additional cancer yield of CBE (3 and 5 % of total cancer cases). These two studies reported lower screen detection (77 and 80 %) compared to the studies in which no additional cases were detected by CBE (screen detection ≥94 %). Current literature on CBE in screening of women at increased risk of breast cancer is insufficient. However, it suggests that the additional cancer yield by performing CBE is minimal or absent. Reconsideration of the role of CBE in intensified screening might be warranted.     

Genetic polymorphisms influencing total and γ′ fibrinogen levels and fibrin clot properties in Africans

Inter‐ethnic variation in fibrinogen levels is hypothesized to be the result of differences in genetic background. No information is available regarding the contribution of genetics to fibrinogen γ′ in Africans. Only limited information is available regarding the interaction between genotypes and total and γ′ fibrinogen concentration in determining fibrin clot properties. Our aim was to investigate the effect of polymorphisms in the fibrinogen and Factor XIII genes on total and γ′ fibrinogen and clot properties (turbidimetry) in 2010 black Africans as well as to determine their interactions. Significant associations were observed between rs1049636 (FGG gene), with total fibrinogen levels and between rs2070011 (FGA promoter area) and fibrinogen γ′ levels. Significant associations were observed between single nucleotide polymorphisms (SNPs) in the FGA (rs2070011), FGB (rs1800787) and FGG (rs1049636) genes and fibre size. Significant interactions were found between total and/or γ′ fibrinogen levels and SNPs in the FGA (rs2070011), FGB (rs2227385, rs1800787, rs1800788, rs4220) and F13A1 genes (rs5985) in determining clot properties. The different SNPs influenced the relationships between total and γ′ fibrinogen levels with clot properties in opposing directions. Genetic influences may be ethnic‐specific and should not only focus on fibrinogen concentration, but also on functionality in determining its role in CVD.