A comparison of serum biochemical changes in two breeds of sheep (Red Masai and Dorper) experimentally infected with Fasciola gigantica.

Twelve Red Masai and 12 Dorper sheep aged between 6 and 9 months, were acquired from a fluke-free area and sheep of each breed divided into two equal groups of six. Each animal in one group of each breed was experimentally infected with 400 viable metacercariae of Fasciola gigantica. The other groups acted as uninfected controls. Blood samples were taken at weekly intervals for the determination of serum bilirubin, albumin, and gamma glutamyl transferase levels. Following the establishment of infection, albumin levels declined in both breeds of infected animals without any significant difference between the two breeds. However, serum bilirubin and gamma glutamyl transferase (GGT) in the infected animals were elevated significantly more in the Dorper than in the Red Masai sheep. Based on these findings, it would appear that Dorper sheep are more susceptible to the infection than Red Masai sheep.

[The functional interrelationships of blood glucose and immunoreactive insulin in the intravenous glucose tolerance test in coronary atherosclerosis patients]. / Funktsional'nye vzaimosviazi gliukozy krovi i immunoreaktivnogo insulina pri vnutrennom teste tolerantnosti k gliukoze u bol'nykh koronarnym aterosklerozom.

Measurements of blood glucose and immunoreactive insulin (IRI) during glucose tolerance test (GTT) in patients with coronary atherosclerosis and with hereditary predisposition to this condition were carried out. The results were processed using programs based on the least squares method, theoretically based on the main assumptions of the probability theory. A strong (virtually linear) correlation between glucose and IRI was detected in the studied groups. Shift of the glucose level by 1 unit in patients with coronary atherosclerosis leads to an almost twofold increase in IRI level, as against subjects with hereditary liability to coronary atherosclerosis. Nonlinear relationship between glucose and IRI in the GTT is described for the control group.

Mood effects of 24-hour tryptophan depletion in healthy first-degree relatives of patients with affective disorders.

BACKGROUND: Acute tryptophan (TRP) depletion was evaluated in healthy volunteers with or without a family history of major affective disorder (FH+ versus FH-). METHODS: Twenty-seven subjects (16 FH+, 11 FH-) received 100 g of an amino acid mixture with and without TRP according to a placebo-controlled, double-blind cross-over design and a diet devoid of TRP for the next 24 hours. RESULTS: The ratio TRP/large neutral amino acids declined to 22% of baseline values after 6 hours, and increased during the night reaching 85% of baseline after 24 hours. Overall, after 6 hours, TRP depletion lead to a lowering of mood, but after 24 hours, these changes were no longer detected. Mood changes and gastrointestinal side effects were significantly more evident in FH+ subjects than in FH- subjects. CONCLUSIONS: Our data support the hypothesis that subjects with a positive family history for depression are predisposed to increased vulnerability to the adverse consequences of serotonergic imbalance.

Lipid reactivity among men with a parental history of myocardial infarction.

In the current study, we examined lipid and cardiovascular responses to an acute stressor among men with and without a parental history of myocardial infarction. 37 men were selected from a large group who completed medical history questionnaires and interviews. Twenty-two men who denied parental history of heart disease (negative parental history) were compared with 15 men with one or both parents who had suffered a myocardial infarction (positive parental history). Total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, heart rate, and blood pressure were measured at rest and during a videotaped speech stressor. Positive parental history men had significantly higher low-density lipoprotein cholesterol levels and blood pressure at baseline, significantly lower high-density lipoprotein cholesterol levels at baseline, and significantly larger total cholesterol and low-density lipoprotein cholesterol reactivity, relative to negative parental history men. Because parental history is a risk factor for subsequent cardiovascular morbidity and mortality, these data suggest that lipid reactivity to stress may be biologically important.

Excessive paternal transmission in psoriatic arthritis.

OBJECTIVE: The differential expression of a disease according to the sex of the disease-transmitting parent has been demonstrated in several autoimmune disorders. The purpose of the present study was to determine whether there are differences in the transmission and expression of psoriatic arthritis (PsA) that are dependent on the sex of the affected parent. METHODS: All probands (patients with PsA) were identified from among the patients attending the University of Toronto Psoriatic Arthritis Clinic. A self-reported family history of psoriasis or PsA was noted for each proband. Differences in parental and offspring transmission with respect to the proband were evaluated. In addition, the expression of PsA according to the sex of the affected parent was assessed at the time of the proband's presentation to the clinic. RESULTS: Ninety-five probands had affected parents: 62 (65%) had an affected father, and 33 (35%) had an affected mother. Thus, the proportion of paternal transmission (0.65) was significantly greater than was expected (0.5) (P = 0.001). Twelve of 74 offspring from male probands (16.2%) were affected with psoriasis or PsA, as compared with 9 of 108 offspring from female probands (8.3%) (P = 0.10). Probands whose fathers were affected had a higher frequency of skin lesions prior to arthritis (P = 0.047), an erythrocyte sedimentation rate > 15 mm/hour (P = 0.044), and a lower incidence of rheumatoid factor (P = 0.044). No differences were noted with respect to age at the onset of psoriasis or PsA, the severity of the PsA, or the frequency of HLA antigens. CONCLUSION: There appears to be excessive paternal transmission in PsA. Further clinical confirmation and elucidation of its genetic basis is warranted.

[A hyperhomocysteinemia study in a population with a familial factor for acute myocardial infarct and sudden cardiac death at a young age]. / Studio dell'iperomocisteinemia in una popolazione con pesante familiarità per infarto miocardico acuto e morte improvvisa cardiaca in giovane età.

The alterations of the metabolism of methionine determining an accumulation of homocysteine in blood (hyperhomocysteinemia) recognize a multifactorial etiology, hereditary as well as acquired. To date several case-control studies have documented that the condition of hyperhomocysteinemia can be considered an independent risk factor of coronary disease and its noxious effects are dose-dependent. It exerts its effect by different mechanisms both prothrombotic and endothelial. In our study we started from an initial cohort of 2227 subjects (1210 males, 1017 females) aged between 45 and 64 years among which we selected 22 persons with at least 2 first-degree relatives below age 50 who had had either a major cardiovascular event (acute myocardial infarction or sudden death) or angiographically documented cardiac disease. We reconstructed the proper pedigrees obtaining 22 families in whom we identified four main subgroups to carry out analyses and comparisons: case-control, composed respectively of all the subjects who survived a major cardiovascular event or a coronary disease documented angiographically and clinically healthy subjects; affected line and non affected line, composed respectively of members belonging to the family line of the proband and members of collateral family line. Each of the subjects involved in the study underwent a complete history regarding job and sports activities, a standardized physical examination, 12-lead digital ECG according to the European Standard Communication Protocol. A blood sample was taken in fasting conditions to determine total cholesterol, HDL and LDL cholesterol, triglycerides, glycemia, fibrinogen, plasma homocysteine. The results indicate how among the cases there were more subjects with homocysteine higher than the 95 degrees percentile in males alone (p = 0.03), the estimated odds ratio calculated from Fisher's test was 8.34 (95% confidence interval 1.32-52.7). Despite the fact that mean age was significantly lower (p = 0.01) in males of the affected line compared to those of the non affected line, the results show much higher homocysteine values in the affected family line in both males and females: a difference quite evident in the distribution especially as regards the 95 degrees percentile. These results obtained in the subjects belonging to the same families emphasize that familial aggregation, which influences the sharing of the genetic patrimony, socio-cultural environment and food habits can induce a differential risk for homocysteinemia. The study of mutations of genes coding for the key enzymes of the metabolism of homocysteine, methylenetetrahydrofolate reductase and cystathionine beta-synthase, which we prepared, will enable use to evaluate the relative influence feeding habits and genetic factors have in the development of hyperhomocysteinemia.

Platelet aggregation in young men with contrasting predisposition to high blood pressure.

In essential hypertension, abnormal platelet function may induce vasospasm and predispose to thrombotic vascular occlusion. We studied in vitro aggregability in platelets from young men with contrasting predisposition to hypertension, defined by their own blood pressure and blood pressures of their parents. Among offspring of parents with low blood pressure, higher blood pressure was associated with impaired aggregation in response to epinephrine (2 x 10(-8) to 5 x 10(-6) mol/L), which was unaffected by endothelin-1 (10(-9) mol/L). By contrast, among offspring of parents with high blood pressure, higher blood pressure was associated with normal aggregation to epinephrine and potentiation of the primary phase of aggregation by endothelin-1. We conclude that enhanced platelet sensitivity to endothelin-1 appears to be a feature of the familial predisposition to hypertension, rather than a nonspecific consequence of high blood pressure.

Seizure-refractory period after a single stimulation and inhibition of seizures after repetitive stimulation in the gerbil: effects on blood cortisol levels.

PURPOSE: To determine the epileptic response of gerbils to external shock stimulus, assessing blood cortisol levels as a parameter to determine stress conditions. METHODS: Five sets of two-month-old Mongolian gerbils were stimulated to elicit seizures by the clapping of a sheaf of papers. Stimulation was done once a week over a 10-week period to obtain a stable situation and a similar response in all the animals. Four of the sets were killed to collect blood samples: those not manipulated; those stimulated twice a day for 5 days; those stimulated once to obtain samples immediately after seizure recovery; and those stimulated once to obtain samples 30 min after seizure recovery. Blood samples from the fifth set of animals were taken in vivo from the retro-orbital plexus. RESULTS: Eliciting seizures with this stimulus, twice a day in a repetitive way, prevented further induced seizures from the second day of stimulation on. Changes in the gerbils' behavior--from exploratory to escape mode--were also observed. The blood cortisol levels found in the sets of animals killed without induced seizures were similar to the others, regardless of whether the animals had been subjected to repetitive stimulation. Additionally, significant decreases in blood cortisol levels were detected in the animals killed immediately and 30 min after recovering from an induced epileptic episode. CONCLUSIONS: The normal refractory period in gerbils can be estimated at 1 h. The lack of correlation between cortisol levels and the inhibition of seizure-elicitation through repetitive stimulation supports the environmental and exploratory hypothesis of seizure generation rather than a stress hypothesis.

Venous thrombosis in older people: prevalence of the factor V gene mutation Q506.

OBJECTIVES: Old age is usually considered to be a risk factor for venous thromboembolism, in conjunction with other factors such as heart failure, major surgery, cancer, long-term immobilization, and antiphospholipid antibodies. Genetic risk factors, especially inherited deficiencies in coagulation inhibitors, also play a role in the pathogenesis of thrombosis, but these are usually diagnosed in thrombophilic patients before the age of 50. The factor V Q506 mutation, responsible for activated protein C resistance, was recently linked to thromboembolic disease. We therefore investigated the prevalence of biological risk factors in older hospital patients with venous thromboembolism. DESIGN: A 2-year study period. SETTING: Ivry sur Seine (Paris), France. PARTICIPANTS: Seventy-nine geriatric patients (60 women and 19 men, mean age 83+/-6.8 years, range 70-102 years) who had had at least one proven episode of venous thromboembolism were enrolled over a 2-year period. MEASUREMENTS: Lupus anticoagulant and antithrombin (AT), protein C (PC), and protein S (PS) levels were determined in plasma. The factor V Q506 mutation was detected on genomic DNA. RESULTS: Lupus anticoagulant was detected in two women, one of whom also had a high level of anticardiolipin IgG, leading to the diagnosis of an antiphospholipid syndrome. No hereditary deficiency in AT, PC, or PS was found, but one patient had an acquired AT deficiency. Interestingly, nine of the 79 patients (11.4%, six women and three men) were heterozygous for the factor V Q506 mutation, although none were homozygous. The only major risk factor for thrombosis identified in these patients was prolonged immobilization in four cases. Four of the nine patients who were heterozygous for the factor V Q506 mutation had recurrent thromboembolism, and two of these patients had been immobilized for long periods. CONCLUSIONS: This study confirms that hereditary deficiencies in coagulation inhibitors, and the lupus anticoagulant, are rarely involved in the pathogenesis of venous thromboembolism in older subjects. In contrast, the factor V Q506 mutation was frequently associated with thrombosis (11.4% of our patients) and should, therefore, be considered an important risk factor in the older people.

Apolipoprotein(a) phenotypes and their predictive value for coronary heart disease: identification of an operative cut-off of apolipoprotein(a) polymorphism.

BACKGROUND: Apolipoprotein(a) isoforms of low-molecular weight are associated with coronary heart disease. However, because of the high number of apolipoprotein(a) isoforms, it is difficult to assess the cardiovascular risk linked to the apolipoprotein(a) gene of a subject; indeed a cut-off of apolipoprotein(a) polymorphism has not been established. The aim of this investigation was to identify an 'operative' cut-off that discriminates apolipoprotein(a) isoforms associated with high genetic risk for coronary heart disease. METHODS: Two hundred and fifty-one patients with coronary heart disease and 284 controls were recruited. Apolipoprotein(a) isoforms were detected using a high-resolution phenotyping method. RESULTS: Twenty-seven apolipoprotein(a) isoforms with apparent molecular weight varying from 280 to 820 kDa were identified. Several cut-offs of apolipoprotein(a) polymorphism were used in order to compare the frequencies of apolipoprotein(a) isoforms of low and high molecular weight between patients and controls: the cut-off between 640 and 655 kDa had the highest chi 2 (130.40). Even when possible differences in apolipoprotein(a) phenotypes (subjects with at least one isoform of low molecular weight and subjects with only isoforms of high molecular weight) were assessed, the same cut-off showed the highest chi 2 (122.47). Multivariate analysis showed that apolipoprotein (a) isoforms had the greatest predictive value for coronary heart disease (F value = 107.0720), when the cut-off between 640 and 655 kDa was used. CONCLUSIONS: The cut-off between 640 and 655 kDa appears to be the most efficient in identifying subjects at high cardiovascular risk linked to apolipoprotein(a) gene, since this cut-off discriminates apolipoprotein(a) isoforms expressing a greater risk for coronary heart disease.

Overt behavior problems and serotonergic function in middle childhood among male and female offspring of alcoholic fathers.

A large body of literature indicates that the serotonergic system is involved in behavioral regulation, as evidenced by the inverse relationship between impulsive aggression and serotonergic function found in adult alcoholics and nonalcoholics. However, studies of this relationship among child and adolescent offspring of alcoholics (COAs) have not previously been done. This study examines the potentially parallel relationship between behavioral dysregulation and low serotonergic function in young COAs. The relationship is of potential interest as a phenotypic marker of biological vulnerability to aggressiveness, which itself has been hypothesized to be a risk factor for later antisocial alcoholism. The present work is part of an ongoing prospective study of the development of risk for alcohol abuse/dependence and other problematic outcomes in a sample of families subtyped by the fathers' alcoholism classification. We examined the relationship between overt behavior problems in middle childhood (mean age = 10.5 +/- 1.7 years) and whole blood serotonin (5-HT) in a subsample of the offspring (N = 32 boys and 12 girls). Using a Child Behavior Checklist (CBCL) index of behavioral undercontrol, we obtained results indicating that high total behavior problem (TBP) children had lower levels of whole blood 5-HT than did low-TBP children (p < 0.01). These results support the hypothesis that there is an inverse relationship between whole blood serotonin levels and behavior problems in young male and female COAs. A father's alcoholism status was not significantly related to his child's 5-HT level, i.e., the child's phenotypic expression of behavioral dysregulation was more reliably connected to serotonergic function than was paternal alcoholism.

[The significance of congenital inhibitor deficiency in acute pancreatitis]. / Znachenie na vrodenata inkhibitorna nedostatuchnost pri ostriia pankreatit.

In the past few years, genotype influence on the occurrence and developmental course of acute pancreatitis is ever more frequently accounted for. Forty-three patients presenting mild (2), medium-severe (33) and severe (6) form of the disease are covered by the study, undertaken with the purpose to assay the role played by some immunoglobulins and polymorphic plasma proteins in this particular disease. In evaluating plasma proteins a deficit of the protease inhibitor Alpha1 antitrypsin is found in twelve patients. However in two cases only Alpha1 antitrypsin deficit is associated with deficiency of the other protease inhibitor--the Alpha2 macroglobulin. In acute pancreatitis patients a genetically determined deficit of protease inhibitory activity is documented, considered a good reason to undertake conservative management using protease inhibitors in the initial phases of the condition.