Subunit structure and activity of glyceraldehyde-3-phosphate dehydrogenase from spinach chloroplasts.

Glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate : NADP+ oxidoreductase (phosphorylating), EC 1.2.1.13) from spinach chloroplasts is a polymeric protein of approx. 600,000 daltons and sodium dodecyl sulphate gel electrophoresis shows that it consists of two subunits of molecular weight 43,000 and 37,000. Comparison of amino acid analyses and tryptic peptide maps indicates that the two subunits have a different primary structure. The native enzyme contains 0.5 mol of NADP+ and 0.5 mol of NAD+ per protomer of 80,000 daltons, no reduced pyridine nucleotides have been detected. Almost complete inactivation is obtained by reaction of two cysteinyl residues per 80,000 daltons with tetrathionate or iodo[14C2]acetic acid; since the same amount of radioactivity is incorporated in the two subunits it is likely that they are both essential for the catalytic activity. Charcoal stripping of native glyceraldehyde-phosphate dehydrogenase produces an apoprotein which still retains most of the enzymatic activity but, unlike the holoenzyme, is gradually inactivated by storage at 4 degrees C and does not react with iodoacetate under the same conditions in which the holoenzyme is completely inactivated.

Cardiac and carotid structure in patients with established hypertension and white-coat hypertension.

AIM: The introduction of ambulatory blood pressure monitoring in the clinical practice has defined a new subgroup of hypertensive patients called white-coat hypertensives. It has been reported that white-coat hypertensives have less cardiac involvement than established hypertensive patients. This study was designed to examine the extent of cardiac and vascular involvement in patients with white-coat hypertension and established hypertension. PATIENTS AND METHODS: We studied 82 patients with mild essential hypertension, never previously treated, using 24-h ambulatory blood pressure monitoring and an echocardiographic and vascular ultrasonographic study. Left ventricular dimensions and mass were obtained according to the Penn convention. The intima-media thickness of the posterior wall of both common carotid arteries was measured 5, 10 and 20 mm caudally to the flow-divider and the average value was used for analysis. RESULTS: Of the 82 patients, 31 (mean +/- SD age 35 +/- 10 years) had average 24-h systolic/diastolic blood pressure values of below 132/85 mmHg (white-coat hypertensives) and 51 (aged 42 +/- 2 years) had a consistently elevated diastolic blood pressure. Both groups had similar body surface area (1.82 +/- 0.22 versus 1.81 +/- 0.22 m2), sex distribution (20 males and 11 females versus 32 males and 19 females), duration of hypertension, metabolic parameters and smoking habit. The 24-h ambulatory blood pressure monitoring values were, by definition, significantly higher in established hypertensives than in white-coat hypertensives (142 +/- 10/94 +/- 6 versus 127 +/- 6/79 +/- 4 mmHg, P<0.001). The left ventricular mass index and intima-media thickness were significantly higher in the established hypertensives (112 +/- 17 g/m2, 0.67 +/- 0.11 mm, respectively) than in the white-coat hypertensives (98 +/- 18 g/m2, 0.58 +/- 0.09 mm; P<0.001 for both). CONCLUSIONS: The prevalence of left ventricular hypertrophy and cardiac remodeling was significantly more frequent in established hypertensives (51%) compared to white-coat hypertensives (19%). These confirm that structural changes in the left ventricle in white-coat hypertensives are more limited than in established hypertensives and show that in white-coat hypertensives there is significantly less involvement of the conductance vessels than in established hypertensives.

Effect of verapamil on atherosclerosis.

Whether antihypertensive agents exert an antiatherosclerotic effect by blood pressure reduction or independently of their antihypertensive effect is clinically relevant. Animal studies have generally shown that the calcium antagonist verapamil has a preventive rather than a therapeutic antiatherosclerotic effect, which is independent of its antihypertensive effect. However, doses used in animal studies were much higher than those administered to humans and, in animals, the time of administration of verapamil coincided with the application of atherogenic stimulus. Human studies have given controversial results. Verapamil appears to effectively reduce the restenosis rate after coronary angioplasty. However, in patients with coronary stenosis who were undergoing bypass surgery, results were conflicting: a retrospective study provided positive results, while a prospective study gave negative results. An ongoing study investigating the effect of verapamil on the carotid arteries of hypertensive patients could help clarify the relationship between blood pressure reduction and the progression, regression or development of carotid lesions.

Evaluating quality of life in hypertensive patients.

The treatment of arterial hypertension is symptomatic in 90-95% of patients, and therefore it must be administered throughout life. At the beginning of pharmacologic treatment when only patients with severe or malignant hypertension are treated, the goal is almost exclusively limited to blood pressure reduction. Thereafter, when the treatment is extended to patients with mild and moderate hypertension, other aims in addition to blood pressure reduction, are evaluated and among these is the impact of pharmacologic blood pressure lowering on the quality of life. The quality of life is recognized as a multi-factorial variable and can be subdivided into six domains. The methodology used to evaluate the quality of life should use valid, repeatable, and sensitive tools. A metaanalysis of well selected and comparable trials has shown that antihypertensive treatment, as a whole, has a small but positive impact on many domains of the quality of life. Furthermore, it appears that converting-enzyme inhibitors, beta-blockers, calcium antagonists, and diuretics cause a statistically significant improvement of quality of life, while centrally acting alpha 1-agonists and direct vasodilators show only a positive trend. Although the comparison among two or more drugs with regard to quality of life is more difficult, it appears from a personal review that converting-enzyme inhibitors and calcium antagonists cause a greater improvement. These two classes of antihypertensive agents have been shown to improve the quality of life in elderly hypertensive patients, together with significant blood pressure reduction. Finally, the incidence of drop-outs and side effects cannot be considered a valid means of evaluation of the quality of life.

[Acute myocardial infarction in young age and drug dependence. Review of the literature and personal experience]. / Infarto miocardico acuto in età giovanile e tossicodipendenze. Revisione della letteratura ed esperienza personale.

UNLABELLED: The authors' personal experience in drug abuse-related acute myocardial infarction (AMI) is reported. STUDY POPULATION: Between January 1991 and May 1994, 6 drug-addict (5 occasional) male patients (pts.) aged 37 +/-3 yrs (Group A) were admitted to our CCU for AMI. Just before hospital admission 4 pts. had inhaled cocaine and 1 had assumed ¿ecstasy¿ tablets; one patient had been heroine-dependent for 5 years and was in an attack of abstinence. The clinical features were compared to those of 17 not drug-addict pts. (Group B) aged <45 years (15 males). DEMOGRAPHIC DATA: In Group A 3/6 pts. were graduated (vs 29.4% in Group B pts.), and nobody belonged to the working class (vs 29.4%); 5/6 pts. (83.3%) were admitted during the week-end (vs 29.4%, p<0.03) and presented a longer time delay between symptoms' onset and hospital admission (7.1 +/- 6.9 hrs in Group A pts. vs 4.7 +/- 4.2 hrs. in Group B pts.). RISK FACTORS: All Group A pts. were smokers (37 +/- 12 cigarettes/day vs 21 +/- 14, p<0.02); 4/6 were heavy alcohol drinkers (vs 29.4%); 1/6 had a family history of ischemic heart disease (vs 35%); nobody was hypertensive(vs 29.4%) or diabetic (vs 5.8%). CLINICAL AND INSTRUMENTAL FINDINGS: On admission, Group A pts. (83.3%) were in Killip class I (vs 82.3%) infarct location was anterior in 3/6 pts. (vs 47%); all pts. were given thrombolitic agents. No significant coronary artery stenosis was found in 3/5 (60%) Group A pts. (vs 23.5% in Group B pts.), where 1 had one-vessel disease (vs 64%%) and 1 had two-vessel disease (vs 11.8%). Ejection fraction was similar in the two groups. No death was observed during follow-up (mean 14.4 +/- 9.6 months, range 3-39 months), 1 patient (Group A) had post AMI angina and reinfarction during coronary angioplasty and 2 pts. continued drug abuse. CONCLUSIONS: AMI in drug addict subjects has to be taken into consideration in particular when the patient is young, male, alcohol consumer, heavy cigarette smoker, and is admitted during the week-end. Further study are warranted to better define therapeutic guidelines.

Outpatient intermittent dobutamine therapy in congestive heart failure.

BACKGROUND: Patients with severe heart failure often progress to the condition where oral agents alone are inadequate to maintain a clinically compensated state. The use of outpatient intravenous inotropic therapy is contentious because it may hasten the progression of the underlying disease or aggravate existing ventricular dysrhythmia. We describe the clinical outcome of 40 pts with severe congestive heart failure (CHF) treated with outpatient dobutamine (D) Therapy. METHODS: Outpatient inotropic therapy with D was started in 40 pts (36 males, 4 females, mean age 56.3±9 years) with chronic CHF and persistence of severe symptoms despite maximal oral therapy. All the pts had required hospitalization with need for i.v. inotropic therapy during the previous 6 months (mean hospital stay 41±28 days).At baseline 35 pts were in NYHA class IV, 5 in class III, mean echo LVEF was 23±5%, cardiac index 1.8±0.4l/min/m(2), pulmonary capillary wedge pressure 22±9.4 mmHg. 18 pts were listed for heart transplantation (HTx). D was infused with portable pumps via permanent i.v. catheters and the mean dose was 3.0±0.83µg/kg/min (range 2-5). The duration of home infusion period was 60±30h/week (range 24-168). RESULTS: During follow-up (mean 393±482 days, range 10-2182) NYHA class improved (III=32-=8). There were 19 hospitalizations in 14 pts (mean hospital stay 12.7±4 days). All the listed pts underwent HTx with 1 intrahospital death, 1 late death (1591 days for lung cancer) and 16 long-term survivors (mean post-operation follow-up 936±215 days). Fourteen not listed pts died after prolonged support (580±252 days - 13 for irreversible HF, accounting for the majority of rehospitalizations and 1 suddenly while not on D infusion). One pt developed non-fatal SVT during D infusion. There were no mechanical or infectious complications related to the device. CONCLUSIONS: Low-dose outpatient D therapy improved NYHA class and decreased hospitalization in pts with refractory CHF without major deleterious effects that may impact adversely on survival on the waiting list.