Apolipoprotein E 3/4 genotype as a cardiac risk marker

Atherosclerosis is a complex disease caused by both genetic and environmental factors. Apolipoprotein E polymorphism is believed to confer substantial susceptibility to coronary heart disease risk. This study was performed on sixty five males selected with normal serum glucose, kidney function, liver function and thyroid function tests. They were classified into: Group A: Apparently healthy individuals [40 subjects], with normal blood pressure and ECG. Group B: Patients with atherosclerotic coronary artery disease [CAD] diagnosed by coronary angiography [25 cases]. All the studied persons were subjected to: serum lipogram, apolipoprotems A-I, B and E concentration and apolipoprotein E genotyping. In CAD group, the mean values of serum total cholesterol triglycerides, LDL-c, TC / HDL-c ratio, LDL-c / HDL-c ratio, apolipoprotein B concentration and apo B /A-I showed significant elevation while HDL-c levels revealed significant reduction compared to apparently healthy group. In CAD group, apo E 3/3 represented 68% of cases, followed by apo E 3/4 genotype 24%, apo E 3/2 genotype 4% and the homozygous apo E 2/2 genotype 4%. In apparently healthy group, apo E 3/3 genotype represented 70%, apo E 3/4; 12.5% and apo E 3/2; 17.5% of the studied individuals. CAD patients carrying apo E 3/3 genotype, had elevations of serum triglycerides, total cholesterol, LDL-c apo B and apo B/A-I ratio in 6%, 47%. 71%, 35% and 12% of cases [respectively] while HDL-c was reduced in 65% of cases carrying this genotype compared to the levels in apparently healthy group. Average risk values of TC/HDL-c ratio were found in 65% of cases and moderate risk values in 35% of cases. High risk values of LDL-c/HDL-c ratio were found in 18% of cases and moderate values in 82% of cases. But carriers of apo E 3/4 genotype in CAD patients had elevated triglycerides, total cholesterol in 33%, 67% of cases respectively and in LDL-c, apo B and apo B/A-I ratio in 83% of cases while HDL-c and apo A-I were reduced in 83% and 67% of cases carrying this genotype respectively. High risk values of TC/HDL-c and LDL-c/HDL-c ratios were observed in 17% and 18% of cases respectively. Other genotype carriers [E3/2 and E2/2] showed no difference when compared to the levels in apparently healthy subjects. In apparently healthy group, apo E 3/4 genotype carriers had significant elevation of serum TC, TG, LDL-c, TC/HDL-c ratio, LDL-c/HDL-c ratio, apo B and apo B/A-I ratio and significant reduction of apo A-I and E concentration than apo E 3/3 genotype carriers. Carriers of E 3/4 genotype also had significant elevation of TC, LDL-c, apo B and apo B/A-I ratio and significant reduction of apo E concentration compared to those carrying apo E 3/2 genotype. 1-Apo E 3/3 is the most common genotype in both apparently healthy subjects and atherosclerotic CAD patients. If is followed by apo E 3/2, then apo E 3/4 genotypes in apparently healthy group, and followed by apo E 3/4, then apo E 3/2 and apo E 2/2 in CAD group. None of the studied individuals had either apo E 4/4 or apo E 2/4 genotypes. 2 -Apolipoprotein E 3/4 genotype carriers had elevated levels of serum total cholesterol triglycerides, LDL-c, apolipoprotein B A apo B/A-I ratio, and reduced levels of HDL-c and apo A-I.So, they are susceptible to more atherogenic lipid profile than other genotype carriers, which is considered a predisposing factor for atherosclerotic coronary artery disease. As regard TC/HDL-c and LDL-c/HDL-c ratios, most of the patients carrying apo E3/4 genotype had high and moderate risk values while patients carrying apo E 3/3 genotype had average and moderate risk values

Lipoprotein a and fibrinolytic parameters in normal and pre-eclamptic pregnancies

This study aimed to evaluate the LP-a and fibrinolytic parameters [plasminogen, fibrinogen and D-dimer] in normotensive and preeclamptic pregnant and non-pregnant women, as well as to assess any association with severity of the disease. The study was carried out in 52 women with age range 17-38 years, including 10 normotensive pregnant women, 31 preeclamptic women [13 with mild preeclampsia [MPE] and 19 with severe preeclampsia [SPE]] and 10 non-pregnant women, as control group. The mean gestational age for MPE, SPE and normotensive pregnant women were 35.5 +/- 3.1 and 36 +/- 1.4 weeks, respectively. In conclusion, LP[a] levels are elevated in preeclampsia and associated with severity of the disease. So, it may serve as a marker of the pathogenic process. Abnormalities in fibrinolytic parameters [fibrinogen and D-dimer] indicated activation of fibrinolysis in response to intravascular coagulation, which may be prevented from reaching its full potential. On the other hand, the absence of significant changes in plasminogen may not be mediated by tissue plasminogen activator [tPA], but by urokinase, whose interaction with PLG is not affected by Lp-a

Soluble as an apoptotic marker in myocardial infarction, the outcome and its relation to high risk, clinical features

This study was designed to detect the impact of apoptosis on prognosis and clinical outcome in patients with myocardial infarction [MI] and its relation to the other risk factors for coronary artery disease. Forty patients [22 males, 18 females] with mean age 53.88 +/- 1.39 years diagnosed as MI on the basis of electrocardiographic and enzymatic changes in addition to the clinical symptoms and signs. Twenty-two patients were smokers. Fifteen healthy volunteers were chosen as a control group. Patients group was classified according to infarct size [expensive MI 62.5%, localized MI 37.5%], presence or absence of heart failure [MI with HF 67.5%, MI without HF 32.5%], presence or absence of diabetes mellitus [DM] [MI with DM 46.5%, MI without DM 52.5%], presence or absence of hypertension [HTN] [MI with HTN 47.5%, MI without HTN 52.5%]. For every participant, history and clinical examination paying special attention to vital signs and cardiopulmonary examination, as well as resting electrocardiogram [ECG] looking for the changes of MI were done. In addition, the following laboratory investigations: Serum sugar, total cholesterol, triglycerides, soluble Apo-1/Fas, homocysteine and nitric oxide [NO] concentrations in serum were assessed. It was concluded that soluble Fas as a marker of myocardial apoptosis is strongly associated with and may be a major determinant of unfavorable early symptomatic post- infarction HF and is related to the size of MI. Homocysteine acts as an independent risk factor for atherosclerotic cardiovascular events and the decreased level of NO is associated with increased risk for development of atherosclerosis, HTN and symptomatic left ventricular [LV] dysfunction

Evaluation of bone turnover in seronegative spondyloarthrpathy [SSPA]: relationship to disease activity

Fifty-seven patients with SSPA were enrolled in this study [33 patients with ankylosing spondylitis [AS], 16 patients with psoriatic arthritis [PsA] and 8 patients with reactive arthritis [ReA]]. The healthy volunteers were served as control. Clinical and radiological status was assessed for each patient. Serum calcium, alkaline phosphatase [ALP] and bone-specific alkaline phosphatase [B-ALP], urinary calcium and free D-pyridinoline cross links [f-Dpyr] were assayed for patients and controls. Urinary excretion of f-Dpyr was significantly increased in AS and ReA, and in AS was correlated with inflammatory measures [ESR and CRP]. In PsA, patients with ESR >30 mm/hour had significantly higher levels of f-Dpyr, than those with ESR <30 mm/hour and those with CRP >6 mg/L than those with CRP <6 mg/L. No significant difference in urinary calcium excretion was observed in the patients groups compared with controls. As regard to bone formation in AS, serum calcium was significantly decreased and ALP, but not B-ALP, level was elevated compared with controls, positive correlation was also found between ALP and inflammatory measure [ESR and CRP]. In PsA patients, a significant increase in serum ALP and B- ALP, but not serum calcium was noted compared with controls. No variation was observed in patients with ReA. Finally, f-Dpyr excretion did not correlate with age, disease duration and no clear difference was observed between men and women. In conclusion, the urinary excretion of bone resorption markers [f-Dpyr] was increased in patients with SSpA, uncoupled by bone formation, particularly in AS, leading to bone loss in those patients and disease activity had a role in this bone turnover

Soluble fas as an apoptotic marker in myocardial infarction: the outcome and its relation to high risk clinical features

In myocardial infarction [MI], activation of soluble fas which is a widely expressed cell surface receptor can induce apoptosis in cardiac myocytes. Apoptosis contributes to myocardiocyte loss in cardiac disease and may be a major determinant for the development of early symptomatic heart failure [HF] but the precise role of apoptosis in the development of cardiac dysfunction need to be established. To detect the impact of apoptosis on prognosis and clinical outcome in patients with myocardial infarction and its relation to the other risk factors for coronary artery disease. Forty patients [22males, 18 females] with mean age 53.88"1.39 years diagnosed as MI on the bases of electrocardiographic and enzymatic changes in addition to the clinical symptoms and signs.Twenty two out of them were smoker. Fifteen healthy volunteers, age and sex matched with the patients as control group has been enrolled in this study. Patient group were classified according to: A- Infarct size [extensive MI 62.5%, localized MT 37.5%]. B- Presence or absence of heart failure [Ml with HF 67.5%, MI without HF 32.5%]. C- Presence or absence of DM [Ml with DM 47.5%, MI without DM 52.5%]. D- Presence or absence of hypertension [Ml with hypertension 47.5%, Ml without hypertension 52.5%]. For every participant, history and clinical examination paying especial attention to vital signs and cardiopulmonary examination, resting electrocardiogram [ECG] looking for the changes of MI and the following laboratory investigation: blood sugar, total choleserol, triglycerides, nitric oxide [NO], Apo-l/fas, and homocysteine concentrations in serum were measured. The serum levels of fas, nitric oxide [NO] and homocysteine are significantly higher in the patients than in the controls [p<0.001]. As regard serum levels of soluble fas in patients with MI, there were significantly higher values in patients with extensive lesion and in those associated with HF when compared to patients with localized lesion and patients not associated with HF respectively [p<0.001]. Serum level of NO was significantly higher in normotensive patients with MI than in hypertensive patients with MI [p<0.001]. Also the serum level of NO was significantly higher in patients with extensive MI than in patients with localizes MI [p<0.001] and significantly higher in patients with compensated heart than in patients with symptomatic HF [p<0.001]. Serum level of homocysteine is significantly higher in normotensive patients with MI and in non diabetic patients with MI when compared to MI patients associated with hypertension or diabetes mellitus [p<0.05, <0.001 respectively]

Soluble interleukin-2 receptor [sIL-2R], tumor necrosis factor alpha [TNF - alpha] and its receptor as prognostic markers in non-hodgkin's lymphoma

This study aimed at assessing whether pretreatment levels of interleukin-6 [IL-6], interleukin-10 [IL-10], tumor necrosis factor-alpha [TNF- alpha], soluble TNF type 1 receptor [p55-R-TNF] and soluble interleukin-2 receptor [sIL-2R] are related to known clinical and biological prognostic factors of lymphoma. Thirty-five patients diagnosed to have non-Hodgkin's lymphoma [NHL] were studied. Patients were treated by 6 cycles of multiagent chemotherapy regimen containing Cyclophosphamide, Adriamycin, Vincristine and Prednisolone [CHOP]. Serum cytokines levels were determined in their serum by an Enzyme Amplified Sensitivity Immunoassay [EASIA] and chemiluminescent enzyme immunometric assay. Statistically significant higher pretreatment levels of sIL-2R [p<0.0001], IL-6 [P<0.0001], IL-10 [p=0.01] and p55-R-TNF [P<0.0001] were observed in NHL patients as compared to controls. sIL- 2R and TNF- alpha levels correlated with tumor burden [P> 0.02 and> 0.01, respectively], while, significantly high levels of IL-6, TNF- alpha and p55-R-TNF were found in patients presented with beta symptoms [P = 0.01, 0.05 and 0.025 respectively]. Following treatment, cytokine levels progressively declined in responding patients. However, no single parameter was found to be of independent prognostic significance. Dramatic variations in sIL- 2 R and TNF- alpha levels between responder and non-responders suggested that combination of these markers might have a prognostic value in management of NHL. These markers could be used in monitoring disease activity and identification of high risk patients who need more aggressive therapy

Study of some aspects of the coagulation system in neonatal septicemia

To study some possible alterations in the coagulation system in neonatal septicemia, 70 newborn infants: 40 with documented septicemia [positive blood culture], 10 with suspected neonatal sepsis [negative blood culture] and 20 full-term healthy newborns were evaluated by clinical examination, blood platelet count, platelet aggregation, screening for coagulation: prothrombin time, thrombin time and partial thromboplastin time, B-thromboglobulin [B TG], Fibronectin [FN], platelet factor 4 [PF 4], protein C [PC], protein S [PS] and thrombin anti- thrombin complex [TAT]. Infants with neonatal septicemia and suspected neonatal sepsis showed significantly lower platelet number and higher platelet aggregation than controls. Patients with documented septicemia showed significantly higher plasma levels of B TG and PF 4 denoting platelet activation. Plasma levels of PC and PS were significantly lower in septicemic newborns than in either newborns with suspected sepsis or controls. Plasma levels of TAT were significantly higher in newborns with septicemia than in newborns with suspected sepsis and controls. FN plasma levels were significantly lower in newborns with septicemia than in both controls or newborns with suspected sepsis. In addition, newborns with suspected sepsis showed significantly lower plasma levels of FN than controls. Newborn with septicemia due to gram-negative organisms showed more significant marked alterations in hemostatic parameters than newborns with septicemia due to gram-positive organisms. Premature septicemic infants showed more significant severe alterations in hemostatic parameters than full-term cases. All bleeders in this study were premature septicemic cases and they showed significant severe alterations in the hemostatic parameters than non-bleeders. The present study suggested activation of the hemostatic system in septicemia especially in prematurely born cases and those with gram negative infections