Serum and urinary activities of two acid glycohydrolases, beta-n-acetyl-glucosaminidase and beta-glucuronidase, were significantly higher in a group of diabetic patients when compared to a control group. No significant differences were found between patients without vascular complications and those with retinopathy and/or large vessel disease, while the highest enzyme levels were present in diabetics in poor metabolic control. In diabetics with nephropathy, urinary excretion of both enzymes was further increased, so that the serum/urine activity ratio (greater than 1 in normal subjects and in diabetics without nephropathy) was inverted (less than 1). These data seem to show that the high activity of these enzymes, commonly observed in diabetes mellitus, is related to the illness rather than to its vascular complications, being higher in patients in poor metabolic control. Furthermore serum/urine activity ratio may be a useful indicator in the monitoring of diabetic nephropathy.

Acetylglucosaminidase↗

PubMedDate not supplied

Serum activity of beta-N-acetylglucosaminidase in obese hyperinsulinemic subjects.

We have measured serum activity of beta-N-acetylglucosaminidase (NAG, fluorimetric method) in some groups of obese subjects with similar degrees of overweight but with different insulin secretion and glucose tolerance (GT) during OGTT. In the control group (35 normal subjects, mean body weight 102% of ideal body weight, normal GT) NAG was 282 +/- 77 nmol S/h/ml; in group I (11 subjects, body weight 149%, normal GT and insulin levels) NAG was 304 +/- 55; in group II (19 subjects, body weight 142%, normal GT and high insulin levels) NAG was 453 +/- 90 (p less than 0.001 vs group I and controls); in group III (14 subjects, body weight 154%, impaired GT and high insulin levels) NAG was 481 +/- 108 (p less than 0.005 vs group I and controls); in group IV (16 subjects, body weight 153%, diabetic GT and high insulin levels) NAG was 657 +/- 109 (p less than 0.001 vs other groups). Moreover in the whole series NAG levels and insulin areas, but not NAG levels and degree of overweight, were significantly correlated (r=0.46, p less than 0.001). These data show that hyperinsulinism (especially when there is also pathological glucose tolerance) can positively affect NAG levels, probably through altered glycoprotein turnover, of which NAG serum levels are a sensitive indicator.

Adolescent↗

PubMedDate not supplied

Correlation between urinary activity of N-acetyl-beta-D-glucosaminidase (NAG) and albumin excretion rate in type II (non-insulin-dependent) diabetic subjects.

Different kidney diseases are often associated with high urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme involved in the breakdown of glycoproteins, whose activity is also increased in diabetic patients with poor metabolic control or vascular complications. In order to evaluate the relationship between renal function and urinary NAG levels in diabetes mellitus, 30 type II diabetic patients without evidence of kidney disease and 18 control subjects were studied. In each subject 24-h urinary excretion rates of NAG (fluorimetric method), albumin and beta 2-microglobulin (radioimmunoassay), together with 51Cr-EDTA clearance were performed. In diabetic patients urinary levels of NAG (356 +/- 25 vs 162 +/- 9.2 nmol/h/mg creatinine, p less than 0.0001) and albumin (21 +/- 2.5 vs 4.3 +/- 0.5 mg/24h, p less than 0.0001) were significantly higher than in the controls, while beta 2-microglobulin levels and 51Cr-EDTA clearance did not differ in the two groups. Moreover in diabetic patients NAG and albumin levels were positively and significantly correlated (r = 0.63, p less than 0.001). These results suggest that urinary NAG excretion rate may be altered early in diabetic patients with apparently normal renal function; its diagnostic value seems to be similar to that of the albumin excretion rate.

Acetylglucosaminidase↗

PubMedDate not supplied

Protective effects of BAY U 3405, a thromboxane A2 receptor antagonist, in endotoxin shock.

The present study was designed to investigate the effects of BAY U 3405, a new thromboxane A2 (TxA2) receptor antagonist, in endotoxin shock. Endotoxin shock (ES) was induced in male rats by an i.v. injection of Salmonella enteritidis lipopolysaccharide (LPS; 20 mg kg-1). LPS administration caused animal death (survival = 0%, 48 h after endotoxin challenge), systemic hypotension, depressed phagocytosis and increased blood levels of TNF-alpha, TxB2 and 6-keto-PGF1 alpha, reduced white blood cell (WBC) count (ES = 5.9 +/- 1 x 10(3) mm-3; CTRL = 13.4 +/- 5 x 10(3) mm-3) and enhanced myeloperoxidase (MPO) activity, studied as a quantitative means for assessing leukocyte accumulation, in the ileum (ES = 0.24 +/- 0.7 U g-1 fresh tissue; CTRL = 0.13 +/- 0.04 U g-1 fresh tissue), in the heart (ES = 0.41 +/- 0.1 U g-1 fresh tissue; CTRL = 0.16 +/- 0.08 U g-1 fresh tissue) and in the lung (ES = 0.68 +/- 0.11 U g-1 fresh tissue; CTRL = 0.19 +/- 0.05 U g-1 fresh tissue). Furthermore, endotoxin administration produced characteristic damage of the gastric mucosa consisting of haemmorrhagic infiltrates. BAY U 3405 (30 mg kg-1 i.v., 30 min before endotoxin challenge) increased survival rate (45% survival rate 48 h after endotoxin challenge), reduced hypotension, decreased TNF-alpha levels in serum, enhanced phagocytic activity (ES = 25.6 +/- 1.9%, BAY U 3405 = 45.9 +/- 0.4%, P < 0.001) and lowered MPO activity in the ileum (0.14 +/- 0.05 U g-1 fresh tissue), in the heart (0.18 +/- 0.08 U g-1 fresh tissue) and in the lung (0.44 +/- 0.09 U g-1 fresh tissue). Finally, the gastric alterations were significantly reduced in rats pretreated with BAY U 3405. These data suggest that this thromboxane receptor antagonist might be a useful drug in shock conditions.

Analysis of Variance↗

PubMedDate not supplied

Effects of gallopamil on epinephrine and norepinephrine plasmatic levels and on TxB2 and beta-tg release in patients with coronary artery disease during adrenergic stimulus with cold pressor test.

We investigated the effect of gallopamil administration during a cold pressor test (CPT) in 18 patients suffering from chronic angina (CA) and in 21 healthy subjects. CA patients showed increased basal levels of beta-thromboglobulin and thromboxane B2 compared to control patients and normal plasma levels of catecholamines. CPT caused plasma catecholamines, beta-thromboglobulin and TxB2 levels to rise. This rise was greater in CA patients than in control patients. Administration of gallopamil (50 mg kg-1 three times a day for 30 days) reduced plasma levels of catecholamines, beta-thromboglobulin and TxB2 blood concentrations either under basal conditions or after CPT. Our data suggest that gallopamil is able to modulate the response induced by adrenergic stress.

Adult↗

PubMedDate not supplied

Soluble E-selectin levels in acute human myocardial infarction.

It has been suggested that leukocyte adhesion mechanisms play a key role in experimental myocardial infarction. We have recently shown that E-selectin, an adhesion molecule belonging to the selectin family, is involved in the pathogenesis of experimental myocardial ischemia. We investigated the circulating levels of E-selectin, studied as a marker of endothelial dysfunction, in acute myocardial infarction. Our study was carried out in 60 patients, 20 hospitalized for acute myocardial infarction, 20 suffered from angina pectoris and 20 healthy control subjects. Patients with acute myocardial infarction had increased serum levels of soluble E-selectin (sE-selectin = 255 +/- 12 ng/ml) compared to both patients with angina pectoris (sE-selectin = 51 +/- 14 ng/ml). Thrombolytic therapy with urokinase (1,000,000 IU as an intravenous bolus in 5 min, followed by producing reperfusion and reduced the serum levels of sE-selectin (71 +/- 19 ng/ml). Our results confirm previous experimental data and indicate that adhesion mechanisms supporting leukocyte-endothelium interaction may also be operative in human acute myocardial infarction.

Adult↗

PubMedDate not supplied

Recombinant human erythropoietin inhibits the cutaneous vasodilatation induced by acetylcholine.

We investigated by means of telethermography the contractile response of cutaneous vessels to recombinant erythropoietin (rHuEPO) and the effects of this hormone on the vasodilatation induced by either acetylcholine, which is endothelium-dependent, and nitroprusside, which is endothelium-independent. Experiments were carried out in 12 healthy volunteers. Graded doses of rHuEPO (25, 50, 500 U/min), acetylcholine (7.5 and 15 micrograms/min), sodium nitroprusside (3 and 10 micrograms/min), and saline solution (sodium chloride 0.9%) were infused in the dorsal pedal artery of the lower limb. rHuEPO reduced the cutaneous temperature in a dose-dependent manner compared to the saline solution, thus suggesting that the hormone causes vasoconstriction. In contrast graded doses of acetylcholine and nitroprusside provoked vasodilatation: in fact both increased the cutaneous temperature compared to controls in a dose-dependent manner. The infusion of vasoconstrictive doses of rHuEPO in association with acetylcholine (15 micrograms/min) reverted the increase in the cutaneous temperature induced by the endothelium-dependent vasodilator. In contrast rHuEPO administered in combination with nitroprusside failed to block the vasodilatation induced by the endothelium-independent vasodilator. Therefore our data suggest that rHuEPO exerts an indirect vasoconstrictive effect and that acetylcholine-induced vasodilatation, which is endothelium-dependent, is blunted by the vasoconstrictive activity of rHuEPO, thus demonstrating that the hormone may impair the synthesis of endothelial nitric oxide.

Acetylcholine↗

PubMedDate not supplied

Recombinant human granulocyte colony-stimulating factor reverts vascular dysfunction.

The aim of our study was to investigate the vascular effects of recombinant human granulocyte colony-stimulating factor (rh G-CSF) in a rat model of irreversible vascular failure. Male anesthetized rats were subjected to the clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock) characterized by high mortality rate (0% survival, 120 min following the release of clamps), a profound hypotension and vascular dysfunction consisting of a marked hyporeactivity to phenylephrine (PE 1 nM-10 microM) of aortic rings. Administration of recombinant human granulocyte colony-stimulating factor (20 micrograms/kg i.v. 5 min after the release of occlusion) increased survival rate (90% 4 h after the release of occlusion), blunted the profound hypotension and reverted the marked vascular dysfunction. Finally, rh G-CSF inhibited the activity of inducible nitric oxide synthase in peritoneal macrophages activated with endotoxin. Our data suggest that rh G-CSF may influence vascular function when low-flow states occur.

Acute Disease↗

PubMedDate not supplied

Occult HBV infection and suppression of HCV replication in the early phase of combination therapy for chronic hepatitis C.

BACKGROUND: Occult HBV infection in subjects with chronic hepatitis C is related to more severe disease outcome. It has been suggested that it might reduce sensitivity to antiviral treatment. AIMS: To assess in HBsAg negative subjects with chronic hepatitis C any effect of the presence of HBV genomes in the liver on the early kinetics of HCV-RNA under PEG-IFN plus ribavirin. PATIENTS AND METHODS: Twenty-two anti-HCV and HCV-RNA positive subjects, with biopsy-proven chronic hepatitis C (M/F 15/7; 50 +/- 8.6 years, 16 genotype 1b) were given PEG-IFN alpha 2b 1.0 microg qw plus ribavirin (800 to 1,200 mg daily according to body weight) for an intended 52 week period. Early virological response was assessed over the first 4 weeks of therapy by quantifying HCV-RNA. Occult HBV infection was assessed by testing for HBV-DNA in the liver before therapy. RESULTS: HBV genomes were found in the liver of 7 of 22 (31.4%) patients, unrelated to anti-HBc status. Kinetics of HCV-RNA during the first 4 weeks of antiviral treatment was unaffected by occult HBV infection, both in terms of absolute reduction of viral load and of number of cases with a reduction of > or = 2 log10 on treatment. CONCLUSIONS: Occult HBV infection does not affect the early phase of response to combination therapy. Further follow-up of patients into the maintenance phase of antiviral treatment and after stopping it will clarify if and when occult HBV has a role in reducing sustained virological response.

Adult↗

PubMedDate not supplied

The late complications of diabetes mellitus.

Late complications of diabetes mellitus include a variety of clinical pictures, mainly related to the involvement of the arterial wall both of large vessels (macroangiopathy) and small vessels (microangiopathy), and of the peripheral nervous system (neuropathy). Their presence in almost all types of diabetes indicates that there is a common pathogenetic mechanism, which can be substantially identified in high blood glucose levels and related alterations. Hyperglycemia, in fact, leads to some metabolic abnormalities, i.e. non-enzymatic glycosylation of proteins and polyol pathway activity; moreover it can negatively affect the pattern of some hormones, especially GH and sex steroids, and normal rheological and clotting properties of blood. These abnormalities, confirmed by experimental models, play a key role in the development of late diabetic complications. However some evidence indicates that a genetic background may predispose to their development or protect from their onset. The two main forms of diabetic retinopathy, non-proliferative and proliferative, show an incidence which increases with age and duration of diabetes, reaching 100% when diabetes lasts for more than 20 years. The risk of blindness, which is very high for the proliferative form, has been dramatically reduced by laser-photocoagulation. Diabetic nephropathy affects a lesser number of diabetics but, after a silent or preclinical stage, leads to renal failure and subsequent replacement therapy. Strict metabolic control in the silent stage and later rigid anti-hypertensive treatment can prevent or retard the evolution of this complication. A close association has been observed between diabetes and hypertension, which can directly affect the onset and evolution of diabetic nephropathy, probably through a common genetic mechanism. Diabetic neuropathy has a wide variety of clinical manifestations, at somatic, autonomic and central levels and can greatly modify the quality and expectancy of life. However, the major cause of death in diabetic subjects is large vessel disease or macroangiopathy, which is similar to non-diabetic atherosclerosis regarding the main histopathological and clinical manifestations but has a much higher prevalence and severity. Finally, a specific cardiomyopathy has also been described in diabetes mellitus and can account for the high rate of heart failure observed in these patients.

Aged↗

PubMedDate not supplied

[Role of protirelin tartrate (TRH-T) in the recovery of post-stroke patients].

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Cerebrovascular Disorders↗

PubMedDate not supplied

Prognostic value of serum thymidine kinase and beta 2 microglobulin in subjects affected by multiple myeloma.

The authors, using a radio-enzymatic and a radio-immunological method, investigated the serum levels of Thymidine Kinase (TK) and Beta 2 Microglobulin (Beta 2M) in 24 subjects affected by Multiple Myeloma (MM) and in 10 controls. The data obtained confirm the good prognostical significance already reported for TK and Beta 2M in subjects with MM. First of all, the results indicate higher levels of TK compared to the controls (9.31 U/l vs 2.9 U/l - p less than 0.005). Similarly, also the levels of Beta 2M indicate a significant increase compared to the healthy subjects. Both TK and Beta 2M levels increased with the progression of the stage of the disease (6.69 mg/ml vs 1.67 mg/ml - p less than 0.005). After therapy there was a significant decrease of TK and Beta 2M levels in responders. Finally, TK demonstrated to be able to detect during the follow-up a possible relapse of the disease.

Adult↗

PubMedDate not supplied

Different daily blood glucose control and free insulin levels during treatment with mixtures of soluble and lente or soluble and NPH semisynthetic human insulins.

To compare daily blood glucose and free-insulin profiles after the administration of two different mixtures of semisynthetic human insulins (soluble + lente or soluble + NPH), 8 well-controlled insulin-dependent diabetic patients with identical basal blood glucose levels were studied. At the beginning of the first daily period of study, each subject was connected to an Artificial Pancreas to achieve a standard blood glucose (100 mg/dl); after at least 4 hours of normoglycemia, feed-back control was interrupted and the insulin mixture injected, at 8 p.m. and 8 a.m., at the dose previously optimised but always in the ratio 1:2 (1/3 rapid-acting + 2/3 intermediate-acting insulin). Blood glucose and free-insulin were then monitored for a 24-hour period, starting from 8 p.m. The same observation was repeated for each patient a few days later, only changing the intermediate-acting insulin. After dinner (8.30 p.m.) and after breakfast (8.30 a.m.) mean blood glucose was lower with soluble + NPH mixture, while early in the morning and in the late afternoon better glycaemic control was achieved with soluble + lente. F-IRI showed an almost specular behaviour: lower values soon after mixture injection and higher levels 8-12 hours later were observed with soluble + lente than with soluble + NPH. These data indicate that, at the ratio 1:2, the mixture of short-acting with lente HM insulin differs from the one with NPH not only for a lower activity of soluble insulin but also for a stronger and more prolonged effect of the intermediate preparation. This difference should be carefully taken into account in clinical practice.

Adult↗