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Biomedical subjects

G Ghirlanda

Publications and source records attributed to G Ghirlanda.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effect of intensive treatment on diabetic nephropathy in patients with type I diabetes.

We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.

Adult↗
PubMed1995

Daily energy metabolism in patients with type 1 diabetes mellitus.

OBJECTIVE: We evaluated the daily energy balance and main substrate utilization in Type 1 insulin dependent diabetic patients and healthy volunteers. METHODS: Ten patients with Type 1 diabetes mellitus and eight healthy volunteers were studied. Diabetic patients were well controlled under intensive insulin treatment (0.6 UI/kg body weight, HbA1c = 5.5 +/- 0.7%). During the 30 hours each subject spent in the respiration chamber VO2, VCO2, respiratory quotient, daily energy intake, 24-hour, day-time, night-time and basal energy expenditure as well as energy expenditure during exercise (at 40% maximal exercise capacity), main substrate oxidation (carbohydrates, lipids and proteins) and overall diet-induced thermogenesis, were measured. The results were corrected for 24-hour urinary nitrogen loss. RESULTS: Diet-induced thermogenesis, expressed as percent of energy intake, was found to be significantly lower in diabetic patients than in control subjects (6.69 +/- 1.29% vs 11.8 +/- 4.71% of energy intake, p < 0.05). A negative correlation was found between diet-induced thermogenesis and daily average glycemia for diabetic patients (r = -0.65, p < 0.01). Energy expenditure during exercise, calculated in terms of net work efficiency, was not different between the two groups. CONCLUSIONS: In conclusion, since diet-induced thermogenesis is highly correlated with the theoretical cost of glucose storage and since no difference was found in carbohydrate oxidation, glucose storage in diabetic patients is probably reduced when hyperglycemia occurs. Diabetic patients in good metabolic control are able to perform mild exercise with a work efficiency very similar to that of control subjects.

Adult↗
PubMed1995

Lactate dehydrogenase activity of platelets in diabetes mellitus.

Lactate dehydrogenase (L-lactate : NAD+ oxidoreductase, EC 1.1.1.27) activity has been measured on the subpopulations of platelets obtained from blood of diabetic patients. Small, but not large platelets show a lactate dehydrogenase activity higher than that of controls. Moreover, a positive statistically significant correlation was found between the activity of small platelets and the percent of glycated haemoglobin, while no correlation was obtained in the case of large platelets. Since we previously demonstrated that lactate dehydrogenase activity of small platelets is exceedingly high in some clinical and experimental conditions, our results not only confirm the involvement of platelets in diabetes but provide more evidence in support of our previous hypothesis of a relationship between lactate dehydrogenase and in-vivo platelet activation.

Adult↗
PubMed1994

Presence and further development of retinal dysfunction after 3-year follow up in IDDM patients without angiographically documented vasculopathy.

Abnormalities in neuroretinal function may play a role in the development of diabetic retinopathy. The natural course of diabetic retinal dysfunction in a group of subjects with insulin-dependent diabetes mellitus and with no apparent microvascular alterations in the retina was followed-up with fluorescein angiography and a sensitive electrophysiological technique, i.e., steady-state focal electroretinogram at the macula, for 3 years. Before the beginning and throughout our study, strict glycaemic control was maintained by three or four daily insulin injections under careful monitoring. Analysis of macular electroretinogram provided information from different neural layers. At the first examination, functional activities of postreceptoral neurons were significantly decreased with respect to those of age-matched control subjects. Diabetic patients showed a functional loss of both ganglion cell (0.53 +/- 0.09 vs 0.42 +/- 0.11 microV; t = 5; p = 0.0001) and preganglion cell (0.51 +/- 0.13 vs 0.42 +/- 0.14 microV; t = 2.8; p = 0.007) layers. Diabetes did not alter photoreceptor activity. After 3 years, dysfunction was significantly greater in the preganglion cell layer (0.28 +/- 0.11 microV; t = 6.3; p = 0.0001). Although in some patients further impairment of ganglion cell function was shown, no significant difference was found in 3 years. Photoreceptor function remained unaltered. No vascular abnormalities in the retina were noted after 3 years in this group of patients. Metabolic control was not correlated to functional changes. Our findings suggest that the middle retinal layer is the most sensitive physiological locus of progressive diabetes-induced dysfunction in the absence of angiographically documented abnormalities.

Adolescent↗
PubMed1994

Evaluation of a rapidly rotating shift system for tolerance of nurses to nightwork.

Fifteen female nurses, aged between 21 and 29 years and employed in an intensive care unit, were examined with the aim of evaluating their psychophysical adaptation to one of the most commonly used, rapidly rotating shift systems, the "metropolitan rota" (2-2-2-2), with the length of the shifts modified according to the work load (including night shifts of 10h) and with the start of the morning shift delayed (to 7 a.m.). Subjective evaluations of work load and psycho-physical conditions as well as performance measures (reaction time, search and memory test), blood pressure and heart rate were recorded at the start, middle and end of the work shifts on the last 4 days of the shift cycle, comprising one morning, one afternoon and two consecutive nights. During the shifts, plasma cortisol and urinary excretion rate of 6-sulphatoxymelatonin, adrenaline and noradrenaline were also recorded, as well as oral temperature and activity-sleep logs. The results showed that this rapidly rotating shift system including two consecutive night shifts does not significantly alter the normal circadian rhythms of the body, particularly as concerns performance levels, body temperature and hormone excretion. Moreover, the lengthening of the night shift to 10h can be considered acceptable in terms of work efficiency, provided that work load is reduced and there are sufficient rest pauses available to compensate for tiredness and sleepiness. On the other hand, the shortening of the day shifts to 7h and the delayed start of the morning shift to 7 a.m. appeared convenient in relation to both work load and sleep duration.

Adult↗
PubMed1994

Early selective neuroretinal disorder in prepubertal type 1 (insulin-dependent) diabetic children without microvascular abnormalities.

The duration of diabetes before puberty is not considered relevant to the future development of complications. To evaluate the effects of diabetes on the neural retina, we analysed macular function by steady-state focal electroretinography in 20 prepubescent diabetic children without vascular retinopathy and in 39 sex- and age-matched normal children. The mean (+/- SD) response related to retinal cellular elements between the photoreceptors and ganglion cells was significantly lower in diabetic children than in the control group (0.38 +/- 0.12 vs. 0.51 +/- 0.13 microV; unpaired t-test = 3; P = 0.005). Similarly, ganglion cell function showed a significant impairment in diabetic children with respect to the control group (0.4 +/- 0.13 vs. 0.53 +/- 0.09 microV; unpaired t-test = 5.4; P = 0.0001), whereas the photoreceptors appeared unaffected. Metabolic control and disease duration were not correlated with functional deficits. Our results suggest that before puberty, early diabetes may have a selective effect on the neural retina prior to the appearance of microvascular changes. A focal electroretinogram could identify diabetic children with neurosensory disorders who may have a higher risk of developing microvascular retinopathy.

Age of Onset↗
PubMed1994

Metabolic implications of coenzyme Q10 in red blood cells and plasma lipoproteins.

Plasma coenzyme Q10 (CoQ10) is currently assayed in our laboratory for its well-known diagnostic meaning; in fact plasma CoQ10 levels are inversely related to metabolic demand. Definite levels of CoQ10 are also found in white and red blood cell components, as well as in platelets. Plasma and erythrocyte CoQ10 has a well assessed antioxidant role, which was demonstrated through a series of experiments. Erythrocytes previously enriched with exogenous CoQ10 were found more resistant to a hemolysis induced by a free radical initiator. Several enzymatic activities of erythrocyte ghosts were also protected by different side chain CoQ homologues, both when reduced and, although at a lesser extent, in the oxidized state. CoQ was not effective in preventing metal-catalyzed oxidation of erythrocyte membrane enzymes, and this effect is likely to be due to lack of interaction of CoQ with the metal target. Moreover CoQ was able to protect isolated enzymes and erythrocyte membrane bound enzymes from the inactivating effect of free radicals generated by water sonolysis or radiolysis. As far as plasma lipoproteins are concerned it is well known that LDL isolated from healthy volunteers supplemented with CoQ10 are more resistant to peroxidation induced by an azoinitiator. We started to systematically investigate CoQ10 and vitamin E levels in isolated human LDL and HDL. Both CoQ10 and vitamin E concentrations, referred to protein, were found higher in LDL than in HDL. Susceptibility to exogenously applied peroxidation did not correlate with the endogeneous content of the two antioxidants, possibly on the basis of different lipid content of these lipoproteins.

Alkaline Phosphatase↗
PubMed1993

Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study.

Inhibitors of HMG-CoA reductase are new safe and effective cholesterol-lowering agents. Elevation of alanine-amino transferase (ALT) and aspartate-amino transferase (AST) has been described in a few cases and a myopathy with elevation of creatinine kinase (CK) has been reported rarely. The inhibition of HMG-CoA reductase affects also the biosynthesis of ubiquinone (CoQ10). We studied two groups of five healthy volunteers treated with 20 mg/day of pravastatin (Squibb, Italy) or simvastatin (MSD) for a month. Then we treated 30 hypercholesterolemic patients in a double-blind controlled study with pravastatin, simvastatin (20 mg/day), or placebo for 3 months. At the beginning, and 3 months thereafter we measured plasma total cholesterol, CoQ10, ALT, AST, CK, and other parameters (urea, creatinine, uric acid, total bilirubin, gamma GT, total protein). Significant changes in the healthy volunteer group were detected for total cholesterol and CoQ10 levels, which underwent about a 40% reduction after the treatment. The same extent of reduction, compared with placebo was measured in hypercholesterolemic patients treated with pravastatin or simvastatin. Our data show that the treatment with HMG-CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage.

Adult↗
PubMed1993

Urinary kallikrein excretion in type 1 (insulin-dependent) diabetes mellitus.

Kidney haemodynamics appear to change after the early phases of diabetic nephropathy: increases in glomerular filtration rate and in renal plasma flow have been widely reported, while kidney size is increased. As the renal kallikrein-kinin system has been demonstrated to regulate kidney blood circulation, we have evaluated the excretion of urinary kallikrein in 87 Type 1 (insulin-dependent) diabetic patients with and without hyperfiltration. Urinary kallikrein excretion was measured in 24-h urine collections. The esterolytic activity was determined by fluorimetric assay. The excretion of urinary kallikreins was significantly higher in hyperfiltering patients (472 +/- 125 esterase units/24 h) than in normofiltering (168 +/- 77 esterase units/24 h) and control subjects (151 +/- 39 esterase units/24 h), p < 0.001. Furthermore, we observed a positive correlation between urinary kallikrein excretion and glomerular filtration rate (r = 0.785). These data suggest that variations of kallikrein and kinin concentrations may play a role in the alteration of renal haemodynamics in Type 1 diabetes. It is possible that the kinin-kallikrein system, the renin-angiotensin system and the prostaglandins may interact to determine the haemodynamic alterations which are present in the diabetic disease.

Adult↗
PubMed1993

Aminotransferases and lactate dehydrogenase in saliva of diabetic patients.

Although inflammatory or degenerative changes in salivary glands have been demonstrated in genetic animal models of diabetes mellitus and in experimental diabetes, no information is available in diabetics on the possible leakage in saliva of cytosolic enzymes as markers of salivary cell injury. Aspartate (GOT) and alanine (GPT) aminotransferases and lactate dehydrogenase (LDH) were determined in saliva samples collected by the Salivette method from well-controlled insulin-dependent (IDDM n = 11) and non-insulin-dependent (NIDDM n = 18) diabetic patients and from age-cross-matched healthy subjects (n = 33). In IDDM salivary concentrations of GOT (112.55 +/- 23.94 UI/L) and LDH (1120.27 +/- 168.31 UI/L) were similar to those found in the NIDDM (90.94 +/- 19.64, and 1255.43 +/- 221.40 UI/L respectively), but higher (p < 0.05) than those observed in normal subjects (33.09 +/- 3.71, and 423.58 +/- 39.94, UI/L respectively). GPT was higher in NIDDM than IDDM, which in turn was higher than in normal subjects (42.78 +/- 14.72, 16.45 +/- 3.74 and 6.85 +/- 1.52 UI/L respectively). Salivary and serum values of GOT, GPT and LDH were not correlated. Determination of cytosolic enzymes in saliva may be useful for monitoring the diabetic involvement of salivary glands.

Adult↗
PubMed1993

Turnover and oxidation rates of plasma-free fatty acids in obese patients treated with dexfenfluramine.

In order to assess a possible direct metabolic effect of dexfenfluramine (dF) apart from its action on food intake reduction, 10 obese postmenopausal women and 10 obese men (BMI = 32.19 +/- 1.99 kg/m2) were studied in a single-blind fashion: 4 weeks on placebo (D-28 to D0) and 4 weeks on dF (D0 to D28). A balanced diet, computed on the basis of basal metabolic rate x 1.4, was followed throughout the study. The patients' alimentary diary was checked for compliance. FFA turnover and oxidation rate, using 1-14C palmitate intravenous infusion, was determined basally (D0), after single high-dose (30 mg, D1) and after long-term (15 mg b.i.d., D28) administration. Indirect calorimetric measurements were performed using a mass spectrometer, and the usual metabolic parameters were computed. The isotope method was used in order to assess plasma FFA oxidation rate. Plasma FFA were analyzed by high-performance liquid chromatography (HPLC) and specific activity was determined at 55, 60, 65 and 70 min by counting dpm in HPLC eluates corresponding to the retention time of palmitate. The turnover rate was not significantly modified after single high-dose dF administration when compared to basal values (6.24 +/- 1.62 at D1 vs. 5.63 +/- 2.07 mmol/kg/min at D0), but was significantly increased at D28 compared with D0 (6.35 +/- 1.96 mmol/kg/min; p < 0.05). A significant increase in FFA oxidation rate was observed with respect to basal values after dF administration both at D1 (0.81 +/- 0.33 at D1 vs. 0.61 +/- 0.21 mmol/kg/min at D0; p < 0.01) and at D28 (0.77 +/- 0.34 mmol/kg/min; p < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Abnormal agonist-stimulated cardiac parasympathetic acetylcholine release in streptozocin-induced diabetes.

We examined the effect of three distinct depolarizing conditions on [3H]ACh release from cardiac postganglionic parasympathetic neurons in age-matched controls and insulin-treated STZ-induced diabetic rats to determine whether alterations in neurotransmitter release were present in the diabetic group. The effect of TTX, which exerts a use- and voltage-dependent block of sodium channels, was examined on the release of ACh stimulated by SRIF14 (preferentially acts at the cell body). We also studied the effect of STZ-induced diabetes on [3H]ACh release by the relatively site-specific depolarizing agent VT (preferentially acts at the axon) and high potassium (non-site-specific). Basal, SRIF14-(10(-7) M), VT-(10(-4) M), and K+ (100 mM)-stimulated [3H]ACh release was similar in control and STZ-induced diabetic animals. However, in STZ-induced diabetic but not control rats, SRIF14-induced [3H]ACh release was resistant to TTX (2 x 10(-7) M). In addition, the response to submaximal K+ (25 mM) stimulation was greater in STZ-induced diabetic compared with control animals. Treatment with insulin corrected these abnormalities. These data indicate that in the acute STZ-induced diabetic rat, SRIF14-, VT-, and high K(+)-evoked release of ACH is not impaired, which suggests that the mechanisms associated with ACh storage and release in postganglionic cardiac parasympathetic neurons are not affected in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Effect of bright light on tolerance to night work.

Fifteen young (mean age 23.4 years) female nurses engaged in a resuscitation unit and working on a fast rotating shift schedule comprising two consecutive night shifts were exposed to short periods (4 x 20 min) of bright light (2350 lx) during their night duty to test a possible positive effect on their tolerance to night work. Two nights with normal lighting (20-380 lx) and two nights with bright light were compared. The following positive effects of bright light upon psychophysical conditions and performance efficiency were noted: in particular, signs of better physical fitness; less tiredness and sleepiness; a more balanced sleep pattern; and higher performance efficiency (letter cancellation test). This result could not be attributed to shifts of the internal clock although the exact cause remains to be determined. In fact, hormonal excretion and body temperature did not show any effect from bright light. In addition melatonin excretion was not suppressed appreciably by the bright light used.

Adult↗
PubMed1992

Lower limb arterio-venous shunts, autonomic neuropathy and diabetic foot.

We have quantitatively assessed the percentage of lower limb arterio-venous (a-v) shunting using a radioisotopic technique and correlated it with autonomic neuropathy evaluated by cardiovascular tests. We have studied three groups of diabetic patients: Group A, 12 non-neuropathic subjects without foot lesions; Group B, 12 neuropathic subjects without foot lesions; Group C, 12 neuropathic subjects with recurrent foot ulcers. Shunting was higher in Group C (10.4 +/- 2.7%) than in Group B (6.8 +/- 2.3%, P less than 0.01) and Group A (3.8 +/- 1.2%, P less than 0.001). Shunts in Group B were higher than in Group A (P less than 0.05). All the tests exploring autonomic function were more impaired in Groups B and C than in Group A, with no difference between Groups B and C. A direct correlation was found between a-v shunting and the following cardiovascular tests: postural hypotension (PH) (r = 0.41, P less than 0.02), sustained handgrip (SH) (r = 0.56, P less than 0.001), deep breathing (DB) (r = 0.40, P less than 0.005) and lying to standing (LS) (r = 0.44, P less than 0.01). A positive correlation was also found between a-v shunts and duration of the disease (r = 0.62, P less than 0.001). Arterio-venous shunting was found to be directly related to autonomic neuropathy even if the higher shunting found in the patients with foot ulcers was not related to a higher degree of autonomic involvement; in addition, this group of patients was characterized by having a more advanced sensory and motor neuropathy. In conclusion, autonomic neuropathy, through its influence on a-v shunts, may play a role in the pathogenesis of diabetic foot, but peripheral neuropathy probably plays a key role in conditioning the development of the overt clinical manifestations of diabetic foot.

Albuminuria↗
PubMed1992

The beta cell function in NIDDM patients with secondary failure: a three year follow-up of combined oral hypoglycemic and insulin therapy.

Eleven Type 2 (non-insulin-dependent) diabetic patients, islet cell autoantibodies negative, nonobese with secondary failure to oral hypoglycemic agents (OHA) [glyburide (7.5 mg/day) and phenformin (75 mg/day)] and HbA1c 10.2 +/- 0.6% were studied. Insulin receptors on circulating monocytes, glucose utilization at supraphysiological insulin concentrations, and plasma C-peptide after i.v. glucagon were evaluated before and after 2 months of combined therapy with OHA and insulin (Ultratard HM Novo). A significant improvement was demonstrated in HbA1c and glycemia after two months of treatment. Glucose MCR was increased after two months of treatment whilst basal C-peptide was decreased as well as receptor binding to monocytes. After three years of combined therapy, body weight, glycemia and HbA1c did not increase. After three years the C-peptide basal values were significantly increased with respect to values found after 2 months of therapy. These results demonstrate that insulin treatment may restore insulin sensitivity in NIDDM patients resistant to OHA treatment and that after three years there is no exhaustion of B-cell function.

Administration, Oral↗
PubMed1992

Nonselective loss of contrast sensitivity in visual system testing in early type I diabetes.

OBJECTIVE: Psychophysical methods in patients with diabetes mellitus reveal deficits of central or foveal vision. Our aim was to evaluate the contrast-sensitivity thresholds in 24 insulin-dependent (type I) diabetic patients with a short disease duration and without retinopathy, taking into account metabolic control. RESEARCH DESIGN AND METHODS: The control group consisted of age-matched nondiabetic subjects. None had visual or systemic symptoms. Contrast sensitivity measured at eight different spatial frequencies to sinusoidal bar patterns of 0.6-12.2 cycles/deg can detect functional defects in the spatially sensitive retinal ganglion cells or in higher visual pathways. We performed two different temporal types of contrast-sensitivity testing, dynamic (8 Hz) and static (0 Hz). RESULTS: Significant losses with dynamic contrast-sensitivity test at all but the highest spatial frequencies (i.e., 12.2 cycles/deg) were shown, whereas there was significant attenuation of contrast sensitivity at five spatial frequencies (1.0, 1.4, 2.2, 7.1, and 9.6 cycles/deg) in the static mode. Grating losses (less than 2SD of control means) of contrast sensitivity were found in 33.3% (dynamic) and in 72.9% (static) of eyes of diabetic patients. HbA1c values were positively correlated at variable spatial frequencies (1.0, 1.4, and 2.2 cycles/deg for dynamic test and 0.6, 1.0, 1.4, 2.2, 4.8, and 7.1 cycles/deg for static test). CONCLUSIONS: Our results suggest an early, generally nonselective neuronal damage of visual pathways that occurs before the onset of clinically detectable retinopathy. The visual deficit may be related directly to the effects of diabetes; repetitive minor hypoglycemic insults may contribute more than a marked hyperglycemic condition to the mechanisms underlying physiological changes along the optic nerve.

Adult↗