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M Lorenzi

Publications and source records attributed to M Lorenzi.

At least 73 records · Page 4Linked to original sources
PubMed1987

High glucose prolongs cell-cycle traversal of cultured human endothelial cells.

There is evidence suggesting that the diabetic state adversely affects replication of certain cell populations. We document that exposure to high ambient glucose (20 mM) induces delay in various phases of the cell cycle of human endothelial cells in primary culture. Cells in S phase were labeled with bromodeoxyuridine (an analogue of thymidine), and the cell-cycle position of the labeled cohort was analyzed by flow cytometry at successive time points. The movement of cells exposed to high glucose for 7-8 days was retarded both in S and G2 phases so that the increase in bromodeoxyuridine-positive cells over 24 h was 1.6-fold, versus 2.0-fold in control cultures. In experiments in which mitotic arrest with vinblastine was used to investigate the movement of cells out of G1 phase without interference from reentering cells, depletion of the G1 compartment was significantly inhibited in cultures grown in high glucose. The effects of chronic high glucose on cell cycle occurred while total protein synthesis was not diminished. Acute exposure to high glucose had no effect on cell-cycle traversal or cell generation time. Cell-cycle abnormalities observed in this study may relate to the DNA damage we have previously observed in endothelial cells exposed to high glucose and, if occurring in vivo, could be of pathogenetic importance for the vascular lesions and teratogenicity of diabetes.

Bromodeoxyuridine↗
PubMed1987

[Muco-purulent cervicitis: a frequent but little-known pathology. Clinical and laboratory considerations].

In order to assess the frequency of cervicitis, to investigate its aetiological causes and to open the debate upon this subject, the authors examined 144 not hospitalized women aging between 18 and 47. They were all in their fertile period and not pregnant. The diagnosis of MPC was given on the basis of the evaluation of the number of polymorphonuclear leukocytes (PNL) found on the endocervical smears, which had been previously coloured by the Gram method: the patients with an average number of PNL greater than 10 per microscopical field at a magnification of 1,000 were considered suffering from MPC, while those with a number of PNL less than 10 formed a group of control. Statistical methods were applied to the two different groups to verify the existence of any relationship between clinical, anamnestic and microbiologic features and MPC. The two groups were compared even after excluding those patients with a presence of Trichomonas vaginalis or yeasts and those suffering from bacterial vaginosis (BV). No significant relationship was found between the isolated microorganisms and MPC, while BV turned out to be related negatively. The objective signs of ectopia and erythema and the pH of the vaginal secretion turned out to be related significantly only after excluding from the selection those patients with a vaginal pathology, while including them, the association turned out to be significant only as to ectopia. The authors point out that: a) MPC represents the most frequent clinical condition; b) the greater part of MPC appears to have an unknown aetiology.

Adolescent↗
PubMed1986

Studies on the permeability of the blood-brain barrier in experimental diabetes.

Whether the increased capillary permeability characteristic of diabetes extends to the blood-brain barrier is presently unclear. We have examined in streptozotocin-diabetic rats the permeability of the blood-brain barrier at the level of 12 discrete brain regions employing 3 intravenous tracers of different molecular weight: sucrose, insulin and horseradish peroxidase. In animals killed 5 min after tracer injection both the sucrose and the inulin spaces were similar to controls. In order to assess whether more prolonged circulation of tracers would uncover leakage, we studied brain spaces at longer intervals after tracer injections. When inulin was allowed to circulate for 15 min prior to killing, animals with 4 weeks of diabetes (but not 2 weeks) exhibited larger inulin spaces at the level of the medio-basal hypothalamus (p less than 0.01), medio-dorsal hypothalamus (p less than 0.05) and periaqueductal gray (p less than 0.01). Horseradish peroxidase, even after 75 min of perfusion, remained confined in both diabetic and control animals to central nervous system areas devoid of blood-brain barrier. Thus, after a relatively short duration of diabetes the blood-brain barrier manifests an increased permeability. It is subtle, limited to some brain regions and selective for low molecular weight tracers.

Animals↗
PubMed1986

Myo-inositol enhances the proliferation of human endothelial cells in culture but fails to prevent the delay induced by high glucose.

Evidence is accumulating, indicating that the abnormal metabolic milieu of diabetes might interfere with orderly replication of some cellular systems and in vitro studies point to a causal contribution of elevated glucose. We had previously shown that human umbilical vein endothelial cells cultured in 20 mmol/L glucose are delayed in achieving saturation density primarily as a consequence of decreased cellular proliferation. We have now addressed whether depletion of myo-inositol--a prevailing consequence of hyperglycemia in other tissues and overcome by provision of supplemental inositol--might play a role in the observed replicative abnormality. Control cultures (5 mmol/L glucose) displayed a dose-dependent response to myo-inositol supplementation that was maximal at concentrations (40 mumol/L) matching physiologic serum levels. The increment in cell number was (mean +/- SD) 141 +/- 20% of control (P less than 0.001), and saturation density was achieved at a cell number 160% higher than in nonsupplemented cultures. Thymidine incorporation and cell cycle studies documented that myo-inositol increased the number of cells cycle studies documented that myo-inositol increased the number of cells engaged in DNA synthesis. These effects of myo-inositol, as well as the dose-response relationship between ambient inositol levels and increments in cell number, were not significantly modified by 20 mmol/L glucose with the exceptions of a transient lesser effect of the physiologic doses during rapid proliferation (day 6) and a larger effect of all doses of myo-inositol in later stages of growth curve (day 12).(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Count↗
PubMed1986

High glucose induces DNA damage in cultured human endothelial cells.

Morphologic and functional abnormalities of vascular endothelium are well recognized in diabetes. In view of our previous finding that high glucose concentrations accelerate death and hamper replication of cultured human endothelial cells, we have investigated in the same model the possibility that exposure to high glucose may result in DNA damage. DNA from human endothelial cells--but not from fibroblasts--exposed to 30 mM glucose for 9-14 d manifested an accelerated rate of unwinding in alkali indicative of an increased number of single strand breaks (P less than 0.001 vs. control). Endothelial cells exposed to high glucose also manifested an increased amount of hydroxy-urea-resistant thymidine incorporation (333 +/- 153 cpm/10(5) cells vs. 88 +/- 42 in control cells, mean +/- SD, P = 0.04), which is indicative of increased DNA repair synthesis. Neither DNA damage nor repair synthesis were increased by medium hypertonicity achieved with 30 mM mannitol. These findings suggest the possibility that, under conditions of high ambient glucose, excess glucose entry in cells that are insulin independent for glucose transport may, directly or indirectly, perturb DNA function. Further, they suggest the possibility that different individual capabilities to repair DNA damage--a process that is under genetic control--may represent a mechanism for different individual susceptibilities to development of diabetic vascular complication.

Cell Count↗
PubMed1986

[Nonspecific vaginitis and Gardnerella vaginalis: methodological and epidemiological notes on 328 cases].

328 samples of vaginal discharges in adult fertile women, aged between 16 and 48, were examined in this trial. After excluding 95 women (39 were affected by vaginal Trichomoniasis, 55 whose discharge presented yeasts and 1 affected by gonococcal infection), the authors divided the remaining 233 cases into subjects affected or not affected by nonspecific vaginitis (NSV) only using a Gram-stained smear. In the 83 patients affected by NSV, the authors isolated Gardnerella vaginalis in the 90.4% of the cases. After statistically correlating the different parameters described in literature as associated to NSV (pH, KOH-test, Clue Cells, isolation of G. vaginalis, symptoms), the authors concluded that: a) Gram-stained smear may be used as a simple microscopical test for diagnosis, in most of the cases, NSV; b) in most of the cases of NSV are implicated more organisms (essentially G. vaginalis and anaerobic organisms); c) G. vaginalis can be considered as a marker of these infections.

Bacteriological Techniques↗
PubMed1985

Altered isoelectric focusing of alpha 2-macroglobulin from plasma of patients with diabetes mellitus.

Plasma from both type I and type II patients with diabetes mellitus displayed elevated alpha 2-macroglobulin trypsin-binding activity relative to normals. Column isoelectric focusing indicated that the average isoelectric point (pI) of the major form of crude alpha 2-macroglobulin was 6.6, 5.9, and 6.2 for normal, type I and type II subjects, respectively. Focused crude diabetic alpha 2-macroglobulin displayed significantly less recovered trypsin-binding activity relative to controls, particularly above a pI value of 6.0. Following preincubation with trypsin, the crude diabetic alpha 2-macroglobulin displayed a single isoelectric form (pI value of 5.3-5.5) and a substantial increase in recovered activity which were both comparable to normal alpha 2-macroglobulin. Purified alpha 2-macroglobulin from both normal and diabetic subjects displayed similar focusing profiles having a distribution of three forms with a pI value of 5.3-5.4 for the principal form. Trypsin-preincubated samples of purified alpha 2-macroglobulin displayed a single form with a pI value of 5.5-6.0. Preincubation of purified normal or diabetic alpha 2-macroglobulin with a plasma preparation devoid of alpha 2-macroglobulin from normal or diabetic plasma resulted in significantly lowered recovery of activity. All of the above studies suggest that the altered focusing properties observed for crude diabetic alpha 2-macroglobulin are due to components of the plasma rather than to alpha 2-macroglobulin itself.

Adult↗
PubMed1985

Racial differences in incidence of juvenile-onset type 1 diabetes: epidemiologic studies in southern California.

We have studied the epidemiologic characteristics of insulin-dependent (Type 1) diabetic patients aged 0-19 in a city (San Diego, southern California, USA) characterized by an impressive racial diversity and especially mild and constant climatic conditions. Ascertainment was through retrospective review of medical records in 19 hospitals. For the 3 years 1978-1981 the mean annual incidence of diabetes was 7.3 cases/100,000, with no statistical difference between the sexes. The observed incidence rates in the various ethnic groups was significantly different from expected (p less than 0.03), with an excess of cases among Caucasians and fewer than expected cases among Mexicans, Blacks and Orientals. There was no identifiable seasonal trend. Some of the clinical characteristics at diagnosis differed between the sexes: males were slightly older (9.3 +/- 5.2 years versus 8.8 +/- 3.9 for females), had a shorter duration of diabetes-related symptoms and a higher frequency of infections both at the time of diabetes diagnosis and in preceding months. Females tended to have a higher frequency of Type 1 diabetes in first-degree relatives. This study documents for the first time that, among multiple racial groups living in the same environment, Caucasians are at the highest risk of developing juvenile-onset Type 1 diabetes.

Asian People↗
PubMed1985

Glucose toxicity for human endothelial cells in culture. Delayed replication, disturbed cell cycle, and accelerated death.

Functional and anatomical abnormalities of endothelium may represent a pathway to the increased vascular permeability and accelerated atherosclerosis characteristic of diabetes. To identify whether and how hyperglycemia may compromise the endothelial barrier, we have employed an in vitro system of human endothelial cells obtained from umbilical veins and cultured in elevated glucose concentrations (20 mM). Under these conditions, the achievement of saturation density was substantially delayed, with cell counts throughout most of the growth curve being 70-80% of control (P less than 0.002). More profound suppression of cell number was present in cultures exposed to 40 mM glucose. Similar, albeit slightly lesser, effects were observed in cultures exposed to 20 mM mannitol, mimicking the hypertonicity of the high glucose media. The effect of elevated glucose and mannitol was primarily mediated by a decrease in overall rate of replication of the endothelium as documented by the lower mitotic index (P less than 0.025). Analysis of the distribution of cells along phases of the cell cycle uncovered in the high glucose cultures a decreased proportion of cells in G0-G1 (70.5 +/- 5% versus 73.2 +/- 4% in controls, P less than 0.05) and an increased proportion of cells in S phase (16.5 +/- 2.7% versus 13.5 +/- 2.2% in controls, P less than 0.01), suggesting that the replicative delay is likely to occur between the phase of DNA synthesis and mitosis. Increased cellular death was specifically observed in the cultures exposed to elevated glucose concentrations (P less than 0.05), but it could account for only a minor portion of the deficit in cell number.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Vessels↗
PubMed1984

Interaction of human endothelial cells with elevated glucose concentrations and native and glycosylated low density lipoproteins.

We have investigated whether and how the elevated glucose concentrations characteristic of diabetes may alter the interaction of endothelial cells with low-density lipoproteins (LDL). Protracted exposure of cultured human endothelial cells to 20 mmol/l glucose failed to affect either the relationship between the degree of confluency of the monolayer and the extent of LDL degradation or the dose-responses for LDL uptake and degradation. In contrast, non-enzymatic glycosylation of LDL by pre-incubation of LDL with glucose markedly inhibited their uptake and degradation by endothelial cells. Thus, at protein concentration of 5 micrograms/ml, the amount of glycosylated 125I-LDL associated with cells was decreased fourfold compared with native 125I-LDL (47 +/- 3 versus 194 +/- 10 ng X mg cell protein-1 X 24 h-1, mean +/- SEM), and degradation was decreased twenty-fold (135 +/- 4 versus 2873 +/- 115 ng X mg cell protein-1 X 24 h-1). The degree of inhibition was proportional to the extent of glycosylation. At all concentrations studied, methylated LDL behaved similarly to glycosylated LDL. The decreased recognition of glycosylated LDL by the endothelial lining of small and large blood vessels may have an impact of tissue physiology and on the overall fate of the glycosylated molecules.

Blood Glucose↗
PubMed1984

Duration of type I diabetes affects glucagon and glucose responses to insulin-induced hypoglycemia.

The glucagon response to hypoglycemia, which fulfills a primary role toward restoring the plasma glucose level, is blunted or absent in most patients with type I diabetes. To identify predictive factors for this abnormality and for the capability of glycemic counterregulation, we investigated the relationship between the duration of diabetes and glucagon and glucose responses to insulin-induced hypoglycemia. In 18 type I diabetic patients with 1 through 28 years of disease who had no detectable autonomic neuropathy, individual glucagon increments after insulin hypoglycemia were inversely correlated with the duration of disease (r = -.53, P < .025). Patients with disease for ten or fewer years showed a glucagon rise that was lower than in controls but significantly higher than in patients with a duration of more than ten years. The plasma glucose rise after the nadir correlated with peak glucagon increments (r = .60, P < .01); eight of the nine patients with glycemic increments comparable to normals had had diabetes for ten years or less. Thus, having diabetes for more than ten years implied that not only were glucagon responses to insulin hypoglycemia severely compromised but also that the abrupt restoration of plasma glucose levels was impaired. These findings should be taken into account when establishing goals and modalities for tight metabolic control.

Adolescent↗
PubMed1982

Stimulatory effects of tolbutamide infusion on plasma glucagon in insulin-dependent diabetic subjects.

The effect of iv tolbutamide on endogenous glucagon levels was measured in nine insulin-dependent diabetic patients chosen because they evidenced no C-peptide response to beta-cell secretagogues. Basal glucagon levels were not suppressed by a sustained tolbutamide infusion; in fact, a slight stimulatory effect was observed at 5, 10, 30, and 45 min. In the absence of detectable insulin secretory capacity and suboptimal insulin replacement, tolbutamide appears to be a stimulus, not a suppressant, of glucagon secretion.

Adult↗
PubMed1981

Effect of naproxen on glucose metabolism and tolbutamide kinetics and dynamics in maturity onset diabetics.

1 The influence of the nonsteroidal anti-inflammatory drug naproxen on glucose metabolism and on tolbutamide pharmacokinetics and pharmacodynamics has been studied in ten maturity-onset diabetics. 2 Comparison of both plasma glucose decay curves and insulin responses during an intravenous glucose tolerance test before and after eight 12 hourly doses of naproxen revealed that naproxen had no significant influence on fasting glucose levels or on rates of glucose elimination. 3 When the subjects were given a combination of naproxen and tolbutamide for 3 days naproxen had no influence on tolbutamide absorption, protein binding, disposition or pharmacological effect. 4 Treatment with tolbutamide in maturity-onset diabetics need not be modified if concurrent administration of naproxen is contemplated.

Adult↗