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Biomedical subjects

M Cacchio

Publications and source records attributed to M Cacchio.

At least 19 recordsLinked to original sources
PubMed2003

Selected contribution: Carotid body as a model for aging studies: is there a link between oxygen and aging?

The carotid body (CB) is the site in the body that triggers awareness of changes in blood oxygen pressure. Aging is characterized by a decrease in oxygen supply to tissues, in reduction of tissue Po2, and in the activity of several enzymes and metabolic factors. The ventilatory response to hypoxia is attenuated with aging related to the age-dependent structure modifications including the basal reduction of oxygen requirements. The aged CB shows an increase in extracellular matrix, a reduction in number and volume of type I cells, and a reduction in volume of mitochondria that was consistent with and similar to that during chronic hypoxia; this phenomenon seems to operate also during aging as shown by the reduced volume of mitochondria in the aged CB. During chronic hypoxia, CB hypertrophy is less evident in aged CB than in young CB. Therefore, hypoxia and aging seem to share some type of link at different cell sites. CB represents an experimental model adequate for studying aging processes because of its high blood flow and metabolism, and thus it serves as a means to understanding the oxygen modulation of the aging process.

Aging↗
PubMed2003

Sustained hypoxia promotes hyperactive response of carotid body in the cat.

Carotid body chemosensory activities were measured before and after 0.2, 5,6 and 7 h of sustained isocapnic (PaCO(2) approximately equal to 30 Torr) hypoxia (PaO(2) approximately equal to 43 Torr) in the cats (n=7). The activity increased from 5.4 impsec(-1) at 0.2 h to about 13 impsec(-1) at 7 h. This increase in chemosensory activities were due to both an augmented sensitivity and to a long-term facilitation and not due to arterial [H(+)] changes.

Animals↗
PubMed2003

Atrial natriuretic peptide stimulates cat carotid body chemoreceptors in vivo.

It is known that atrial natriuretic peptide (ANP) is released from cardiac myocyte and other stores during hypoxia and is involved in pulmonary-cardiovascular reflexes and in natriuresis and diuresis. Since the carotid body initiates hypoxic chemoreflexes, we hypothesized that ANP could potentiate the hypoxic stimulation of the carotid body chemoreceptor in vivo. We studied the effect of close intra-arterial injection of ANP on carotid chemoreceptor activity in anesthetized male cats which were paralyzed and artificially ventilated. Graded doses of ANP (0-10 nmoles) were administered by intra-arterial injections and they produced an excitatory response. Single dose of ANP (6.5 nmoles) at four steady-state levels of arterial PO(2), at constant PCO(2), produced increases of chemoreceptor activity. This increase of chemoreceptor activity with ANP in the presence of CO(2)-HCO(3)(-) in vitro could make a difference from those without CO(2)-HCO(3)(-) in vivo.

Adaptation, Physiological↗
PubMed2003

Oxygen supply modulates MCP-1 release in monocytes from young and aged rats: decrease of MCP-1 transcription and translation is age-related.

Hyper or hypoxia may affect the immune system's chemokine production. Monocyte chemotactic protein-1 (MCP-1), an important chemotactic cytokine can be activated by active oxygen species. Groups of rats were exposed to hypoxic and hyperoxic environmental conditions for 60 h and MCP-1 was determined in their peripheral blood mononuclear cells by Elisa and Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). In this study we evaluated if the ability of monocytes to produce MCP-1 under basal conditions or after stimulation with lipopolysaccharide (LPS) or phytohaemagglutinin (PHA) was differently affected by exposure to hyper or hypoxic conditions in young and aged rats. MCP-1 expression and production in monocyte/macrophages from rats at normoxic conditions was reduced in aged subjects. However, spontaneous, LPS or PHA-induced MCP-1 production was up-regulated by exposure to hyperoxic conditions in both young (62 +/- 8, 99 +/- 7, 102 +/- 8 pg/ml, respectively) and aged rats (79 +/- 4, 112 +/- 9, 117 +/- 10 pg/ ml, respectively). We conclude that hyperoxia is an important regulator of MCP-1 release and support the hypothesis that increased % of O2 may serve to initiate MCP-1 production which then serves to recruit and regulate the distribution of mononuclear cells to the sites of inflammation.

Aging↗
PubMed2001

Oxygen-free radical decrease in hypertensive patients treated with lercanidipine.

BACKGROUND: The relationship between oxidative stress, lipoproteins, cardiovascular risk factors and vascular disease progression has recently attracted fresh attention due to the possibility of measuring free radicals (FRs). The aim of this study was to evaluate blood plasma variations in oxygen FRs in hypertensive patients treated with lercanidipine, a drug acting on blood pressure and microcirculation. METHODS: Twenty-two patients with moderate hypertension (M:F=12:10; age=52) and no vascular disease (evaluated by high-resolution ultrasound) were treated for 24 weeks with Lercanidipine (10 mg/day or 20 mg/day if BP values did not decrease at least 15 percent after four weeks of treatment). BP was measured at inclusion and after 4, 8, 12 and 24 weeks of treatment. FRs measurements (using the D-Roms test) were made at inclusion, at the 8th, 12th and 24th week. RESULTS: All patients completed the treatment which was well tolerated and without side effects. Systolic and diastolic BP decreased after 8, 12 (p<0.05) and 24 weeks (at 24 weeks systolic pressure was decreased by 21.1 percent, and diastolic by 11.1 percent; p<0.02). FRs levels progressively decreased from 541 Carr Units (SD 54) at inclusion to 411 (SD 56) at eight weeks (p<0.05), to 401 (SD 35) (p<0.05) at 12 weeks and finally to 398 (SD 33), (p<0.02) at 24 weeks of treatment (72.2 percent of the initial value). CONCLUSIONS: The possibility of measuring FRs in vivo with a simple, inexpensive test allows the identification of subjects with a high level of oxidative stress, and the monitoring of the effects of treatments. Lercanidipine, acting on blood pressure, on the microcirculation and decreasing oxidative stress and Frs plasma levels may effectively decrease the rate of progression of cardiovascular diseases offering the advantage of an increased level of protection in patients with high levels of oxidative stress.

Adult↗
PubMed2001

Effects of the total triterpenic fraction of Centella asiatica in venous hypertensive microangiopathy: a prospective, placebo-controlled, randomized trial.

The aim of this study was to demonstrate whether total triterpenic fraction of Centella asiatica (TTFCA), was effective in improving the microcirculation in venous hypertension and microangiopathy. Forty patients with severe venous hypertension, ankle swelling, lipodermatosclerosis were included. After informed consent, patients were randomized into a treatment and a placebo group: those in the treatment group received TTFCA (tablets, 60 mg, twice daily for 8 weeks). The two groups of subjects were comparable for age and sex distribution. The mean age was 48 years (SD 9; M:F= 11:11) in the treatment group (22 patients) and 47.6 (SD 7; M:F= 10:8) in the placebo group (18 patients). There were no differences between placebo and treatment group at inclusion; there was no change between inclusion and measurements at 8 weeks in the placebo group. A decrease (p < 0.05) in RF (flux at rest) and RAS (rate of ankle swelling) were observed in the treatment group. The decrease in capillary filtration was associated with improvement in signs and symptoms (p < 0.05). The difference in flux, signs and symptoms, and filtration was clinically important at 8 weeks. No side effects were observed. In conclusion venous microangiopathy was improved by TTFCA treatment.

Administration, Oral↗
PubMed2001

Methods of evaluation and quantification of microangiopathy in high perfusion microangiopathy (chronic venous insufficiency and diabetic microangiopathy).

Noninvasive tests have been developed to provide qualitative and quantitative information that can offer answers to most questions posed in venous diseases. While duplex scanning is used to assess the macrocirculation, microcirculatory methods assess and quantify venous microangiopathy. Laser Doppler flowmetry is used to assess tissue viability and perfusion. Transcutaneous PO2 and PCO2 measurements are used to study venous hypertension, and strain-gauge plethysmography (SGP) is used to assess capillary filtration. In venous hypertension fluid filtration into the extracapillary compartment is increased. The increase in filtration is associated with a decreased venoarteriolar response. To quantify capillary filtration two methods have been developed: venous occlusion plethysmography and rate of ankle swelling. These methods quantify filtration into the extracapillary compartment and therefore are an indication of the formation of edema, which is the most frequent sign of venous hypertension. Other methods such as the vacuum suction chamber and the edema tester can be used to assess changes due to treatment in chronic venous hypertension. These methods have been used and validated in several experimental and clinical studies. The techniques described in this article were used in controlled environmental conditions. Results were consistent with clinical problems and data from previous studies from our group and from data from other investigators.

Blood Gas Monitoring, Transcutaneous↗
PubMed2001

Flight microangiopathy in medium- to long-distance flights: prevention of edema and microcirculation alterations with total triterpenic fraction of Centella asiatica.

The aim of this study was the evaluation of microcirculatory alterations associated with edema in passengers travelling for more than 3 hours and the study of the effects of TTFCA (total triterpenic fraction of Centella asiatica) on the development of microcirculation alterations and edema, in a prospective, randomized study. Laser Doppler flowmetry (LDF), transcutaneous PO2 and PCO2, rate of ankle swelling (RAS) were used. Subjects were randomized after informed consent into two groups: one control group (no drug or other treatment), and a treatment group (TTFCA 60 mg thrice daily for 2 days before the flight, the day of the flight, and for another day after the flight). Inclusion criteria were age range between 30 and 50, mild-moderate superficial venous disease with varicose veins. Subjects traveled in economy class. In controls there was a progressive increase in CO2, RAS, and edema score and a progressive decrease in flux (RF) and venoarteriolar response with flying time. The variations in all parameters were milder (p>0.05) in the TTFCA group. RAS and edema were significantly lower in the TTFCA-treated group (p<0.025). The progressive increase in RAS, PCO2, and the decrease in VAR and O2 were linearly associated with flight time (up to 10 hours). These results are very interesting and indicate an option for patients prone to edema and microcirculation disturbances during long flights.

Adult↗
PubMed2001

Capillary filtration in venous hypertension: evaluation with the vacuum suction chamber device and strain-gauge plethysmography.

The aim of this study was to evaluate local capillary filtration with the vacuum suction chamber (VSC) and the rate of ankle swelling (RAS) in patients with ankle edema due to venous hypertension before and after treatment with oral TTFCA (60 mg tablets twice daily) for 4 weeks. Strain-gauge plethysmography (SGP) was used to assess RAS and local capillary filtration was studied with the VSC (applied on the perimalleolar region); the disappearance of the weal was measured (minutes). Fifty patients with chronic venous insufficiency and edema were included (M:F= 25:25) after informed consent and randomized into a treatment (mean age 43; SD 7) and a control (mean age 44; SD 8) group. Compliance was very good (100% completed the 4-week trial); no side effects were observed. The two groups were comparable for age/sex distribution. Values of RAS and VSC time were comparable in the two groups, at inclusion. After 4 weeks there were no changes in the control group. A significant reduction was observed in the treatment (RAS decreased to 34% of the initial value; the VSC time decreased 48%; p<0.02). Treatment with TTFCA in chronic venous insufficiency is useful as soon as edema is detected to control the progressive alterations leading to ulcerations. This action is produced by complex actions on the microcirculation reducing and controlling edema and modulating collagen synthesis. This results in an improvement of the microcirculation, skin and subcutaneous tissue perfusion and functions.

Adult↗
PubMed2001

Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcPO2-CO2, and leg volumetry.

The aim of this prospective, randomized study was to demonstrate whether an oral preparation of TTFCA was effective in improving the microcirculation and edema (leg volume) in venous microangiopathy. Forty patients with venous hypertension were included. Treatment was prescribed for 6 weeks (tablets, 60 mg twice daily). Patients were randomized into a treatment and a placebo group. There were 20 patients in each group. In the treatment group the mean age was 42 (SD 7; M:F = 10:10); in the placebo group, the mean age was 40 (SD 9; M:F = 10:10). Tolerability and compliance were very good; there were no dropouts. At inclusion there were no differences between placebo and treatment group. After treatment there was a decrease in resting flux (29%) and an improvement (increase) in venoarteriolar response (52%); PO2 was increased (7.2%) and PCO2 decreased (9.6%). There was an important decrease in leg volume (66 mL decrease; 1.3% volume variation). The difference in flux, O2-CO2 and volume parameters were significant and clinically important at 6 weeks in the treatment group. In conclusion, TTFCA improves microcirculation and leg volume in venous hypertension. The effects of TTFCA are observed even in a limited sample of patients.

Adult↗
PubMed2001

Treatment of edema and increased capillary filtration in venous hypertension with total triterpenic fraction of Centella asiatica: a clinical, prospective, placebo-controlled, randomized, dose-ranging trial.

The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) was evaluated in three groups of patients with venous hypertension (ambulatory venous pressure >42 mm Hg) and in a group of normal subjects before and after treatment for 4 weeks with total triterpenic fraction of Centella asiatica (TTFCA), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (20 patients)was treated with TTFCA 60 mg thrice daily, group B (20 patients) was treated with 30 mg thrice daily; group C (12 patients) was treated with placebo; and group D (10 normal subjects) was treated with TTFCA 60 mg thrice daily in a randomized study. Capillary filtration rate was assessed by venous occlusion plethysmography, ankle edema by a new system called AET (ankle edema tester). Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC, and AE were significantly higher in patients in comparison with normal subjects. After 4 weeks of TTFCA treatment, there was a significant decrease of CFR, AC, and AET time in patients. This was also greater in the higher dose group. No significant change was observed in the placebo group and in normal subjects treated with TTFCA. Symptoms were also significantly improved in the two groups treated with the active drug according to the dose. No significant changes were observed in the placebo group. In conclusion, the improvement of signs and symptoms by TTFCA observed in patients with venous hypertension was well correlated with the improvement of CFR and ankle edema. Dose ranging showed that 180 mg/day is more effective in improving symptoms and CFR.

Adult↗
PubMed2001

Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined microcirculatory model.

A single-blind, placebo-controlled, randomized study was performed on the effects of different doses of the total triterpenic fraction of Centella asiatica (TTFCA) in patients with venous hypertensive microangiopathy. A combined microcirculatory model that considers laser Doppler flowmetry (LDF) and transcutaneous oxygen (PO2), transcutaneous carbon dioxide tension (PCO2) measurements was combined with the symptom evaluation. LDF tests included the baseline resting flow, the venoarteriolar reflex, and the variation of flow related to the temperature increase. All tests provided a significant difference between drug-treated groups and the placebo group, thereby allowing a distinction to be made between the higher (120 mg daily) and the lower (60 mg daily) dose of TTFCA. Transcutaneous PO2-PCO2 measurements were significantly modified by drug treatments, while no variation could be detected in the placebo group. Important symptomatologic effects (evaluated by subjective scores) followed TTFCA administration, especially at the higher dose level, while no effect was obtained with placebo. The trend of symptom evaluation paralleled the results of objective tests of our microcirculatory model, providing evidence that this model can reveal effects of venoactive drugs on venous hypertensive microangiopathy. TTFCA displays a significant activity. Doses as high as 120 mg daily may be safely used in venous hypertension.

Adult↗
PubMed2001

Total triterpenic fraction of Centella asiatica in chronic venous insufficiency and in high-perfusion microangiopathy.

Total triterpenic fraction of Centella asiatica (TTFCA) is effective in improving venous wall alterations in chronic venous hypertension and in protecting the venous endothelium. TTFCA is active on connective tissue modulation, improves the synthesis of collagen and other tissue proteins by modulating the action of fibroblasts in the vein wall, and stimulates collagen remodeling in and around the venous wall. This is due to the modulating action of TTFCA on fibroblasts as shown by experiments on the growth of human embryonal fibroblasts. TTFCA has a moderate in-vitro and in-vivo stimulating effect on collagen synthesis and, at higher dosages, an inhibition on the synthesis of collagen and acid mucopolysaccharides. Studies have indicated the role of TTFCA on the synthesis of specific venous wall elements by cell cultures of human embryonal fibroblasts. The tissue-stimulating action is shown by the increased collagen production independent from the stimulation of cell proliferation (this differentiates the action of TTFCA from cell growth factors). TTFCA is active on the microcirculation in venous and diabetic microangiopathy. Signs and symptoms of venous hypertension and edema are improved by treatment. The remodeling on collagen synthesis could be one of the possible mechanisms of actions of TTFCA in the remodeling of echolucent (soft; therefore, with risk of thrombosis and embolization) plaques at the carotid and femoral bifurcation. This compound is safe and well tolerated. In conclusion, several actions of TTFCA in vascular diseases makes the use of this compound very interesting in venous and arterial problems.

Chronic Disease↗
PubMed1995

Double effect of ethanol on intracellular Ca2+ levels in undifferentiated PC12 cells.

In PC12, a cellular line derived from a rat pheochromocytoma, ethanol (EtOH) induces a different effect depending on the concentration used. When resting cells are incubated with an alcohol concentration less than or equal to 120 mM, the [Ca2+]i increased with a double phase pattern. If the alcohol concentration was increased over 120-160 mM, EtOH reversed its effect and the [Ca2+]i decreased. This decrease was strongly inhibited if KCl-depolarized cells were used and was completely abolished if the substrate constituted EtOH-chronically treated cells. The Ca2+ increase is the consequence of an activation of L-type voltage-activated channels, while the other voltage-dependent channels (N-type), the receptor-operated channels and the Ca2+ extrusion pump present in these cells are not involved in EtOH action. These findings indicate that EtOH can induce (by different mechanisms) both potentiating and inhibiting effects on [Ca2+]i in PC12 cells in relation to the alcohol dose effectively present in the suspension medium.

Adrenal Gland Neoplasms↗
PubMed1981

[Findings of the importance of dietetic fiber in the regulation of cholesterolemia].

We studied the variations of some lipid indexes in cholesterolemia, lipidemia and triglycerides in relation to a diet rich in bulk. Seven adult male subjects in good health were tested for cholesterol, lipid and triglycerides before and after a two week period of a dialy diet of 40 g of whole wheat bran containing about 10g of fiber. At the some time the lipid, cholesterol and triglycerides limits were measured in 3 groups of rabbits. The first groups was subjected to a normal diet, the second group was subjected to a diet of bleached flour and vitamins, and the third group had a diet similar to the second group but with the addition of 40 g whole wheat bran. The results of our investigation demonstrated a statistically significant decrease of cholesterol lipid and triglycerides levels the special diets at the some time we did not see in increase in the third group of rabbit. Our study seems to indicate that dietetic fibers exercise a vital role in regulating the concentration of plasma lipids even if the subject continues to consume a diet rich in fats. From this we see to importance of the dietetic fibers as a protective factor in the prevention of ateriosclerotic.

Adult↗
PubMed1981

[Evaluation of various hematologic parameters in Andean miners (Morococha-Peru 4560 m)].

In other Author's previous studies refer that prolonged CO exposure, as chronic altitude exposure, causes marked increases in Hb and Htc levels. We had intended to study these hematologic changes on three non-smokers' group : Miners of the Andes working at CO exposure ambients, Residents and European Subjects living a. s. l. and exposed at 4560 m. Statistical analysis, according with literature, has shown significant difference in the three groups' Hb and Htc ratio, in comparison with sea level control values. We had moreover observed that HbCO of the Miners' group reached, sometimes, 8, 2% values. It does not seem, however, that the higher HbCO levels noted in the Miners' group are sufficiently elevated for producing a further increase in Hb and Htc ratio compared to the other two control group.

Adult↗