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Biomedical subjects

F M Ruggiero

Publications and source records attributed to F M Ruggiero.

At least 19 recordsLinked to original sources
PubMed1998

Peroxidative damage to cardiac mitochondria: cytochrome oxidase and cardiolipin alterations.

Rat heart mitochondrial membranes exposed to the free radicals generating system tert-butylhydroperoxide/Cu2+ undergo lipid peroxidation as evidenced by the accumulation of thyobarbituric acid reactive substances. Mitochondrial lipid peroxidation resulted in a marked loss of both cytochrome c oxidase activity and cardiolipin content. The alterations in the properties of cytochrome c oxidase were confined to a decrease in the maximal activity (Vmax) with no change in the affinity (Km) with respect to the substrate cytochrome c. Various lipid soluble antioxidants could prevent the lipid peroxidation reaction and the associated loss of cytochrome c oxidase activity. External added cardiolipin but no other phospholipids, nor peroxidized cardiolipin was able to prevent the loss of cytochrome oxidase activity induced by lipid peroxidation. These results establish a close correlation between oxidative damage to cardiolipin and alterations in the cytochrome oxidase activity and may prove useful in probing molecular mechanism of free radicals induced peroxidative damage of mitochondria which has been proposed to contribute to aging and to chronic degenerative diseases.

Animals↗
PubMed1998

Monoclonal antibody to lymphocyte function associated antigen-1 improves graft-versus-host disease.

UNLABELLED: We previously showed that intestinal tissue expression of lymphocyte function associated antigen-1 is increased in animals with graft-versus-host disease after small-bowel transplantation. HYPOTHESIS: Treatment of rats with monoclonal antibody to lymphocyte function associated antigen-1 after small-bowel transplantation will lessen the severity of graft-versus-host disease. METHODS: Graft-versus-host disease was created in Lewis X Brown-Norway F1 rats by heterotopic vascularized small-bowel transplantation from Lewis donors. Transplanted rats were treated with either saline or various regimens of monoclonal antibody to lymphocyte function associated antigen-1. Clinical characteristics, weight loss, spleen index, white blood cell counts, native intestinal histology, bowel permeability, and survival were then compared between groups and appropriate sham-operated and lymphocyte function associated antigen-1-treated controls. RESULTS: Lymphocyte function associated antigen-1-treated rats lost less weight, had larger spleen indexes, more normal white blood cell counts, more normal native intestinal histology, less alteration in bowel permeability, and longer survival than untreated small-bowel transplantation rats. CONCLUSIONS: In this model of graft-versus-host disease after small-bowel transplantation, monoclonal antibody to lymphocyte function associated antigen-1 treatment decreased the severity of graft-versus-host disease and prolonged rat survival.

Animals↗
PubMed1998

Increased LFA-1 expression in intestines of rats with GVHD after small bowel transplantation.

Experimental graft-versus-host disease (GVHD) causes immune-mediated intestinal injury. The adhesion molecule lymphocyte function associated antigen-1 (LFA-1) is involved in leukocyte homing to areas of inflammatory injury. Our hypothesis was that LFA-1 is increased in the GVHD injured small bowel and colon. We found that animals with GVHD caused by auxiliary small bowel transplantation displayed significantly increased expression of intestinal LFA-1alpha at times of clinical illness when compared to controls. The staining pattern progressed from a few discretely stained cells in the lamina propria on day 5 to diffuse confluent staining of lamina propria on day 13 and was statistically significantly increased from controls at days 10 and 13. CyA-treated animals had intermediate staining between control and day 13 GVHD animals. There was no difference between sham-operated control animals and SBTx animals with GVHD in the amount of staining for LFA-1 in extraintestinal organs normally affected by GVHD. We conclude that: (1) LFA-1 expression in the small bowel and colon progressively increased during GVHD after SBTx; and (2) CyA treatment is associated with decreased LFA-1 expression in the small bowel and colon of GVHD animals after SBTx. LFA-1 may play an important role in immune-mediated injury of the intestine.

Animals↗
PubMed1997

Alterations in carnitine-acylcarnitine translocase activity and in phospholipid composition in heart mitochondria from hypothyroid rats.

Changes in mitochondrial fatty acid metabolism may underlie the decline in cardiac function in the hypothyroid animals. The effect of hypothyroidism on fatty acid oxidation, carnitine-acylcarnitine translocase activity and lipid composition in rat heart mitochondria has been examined. Rates of mitochondrial fatty acid oxidation as well as carnitine-carnitine and carnitine-palmitoylcarnitine exchange reactions were all depressed in heart mitochondria isolated from hypothyroid rats. Kinetic analysis of the carnitine-carnitine exchange reaction showed that the hypothyroid state affects the Vmax of this process, while having no effect on the K(m) value. Heart mitochondrial inner membrane lipid composition was significantly altered in hypothyroid rats. Cardiolipin, particularly, was found to decrease (by around 36%). Alterations in fatty acid pattern of mitochondrial inner membrane preparations from hypothyroid rats were also found. The effects of the hypothyroid state on fatty acids oxidation, carnitine translocase activity and phospholipid composition were completely reversed by following treatment of hypothyroid rats with thyroid hormone. A lower cardiolipin content in the mitochondrial inner membrane offers a plausible mechanism to explain the decline in the translocase activity in hypothyroidism.

Animals↗
PubMed1997

Age-dependent decline in the cytochrome c oxidase activity in rat heart mitochondria: role of cardiolipin.

Cardiolipin is a major mitochondrial membrane lipid and plays a pivotal role in mitochondrial function. We have recently suggested a possible involvement of this phospholipid in the age-linked decline of cytochrome c oxidase activity in rat heart mitochondria [G. Paradies et al. (1993) Arch. Gerontol. Geriatr. 16, 263-272]. The aim of this work was to test our earlier proposal. We have investigated whether addition of exogenous cardiolipin to mitochondria is able to reverse, in situ, the age-linked decrease in the cytochrome oxidase activity. The method of fusion of liposomes with mitochondria developed by Hackenbrock [Hackenbrock and Chazotte (1986) Methods Enzymol. 125, 35-45] was employed in order to enrich the mitochondria cardiolipin content. We demonstrate that the lower cytochrome c oxidase activity in heart mitochondria from aged rats can be fully restored to the level of young control rats by exogenously added cardiolipin. No restoration was obtained with other phospholipids or with peroxidized cardiolipin. Our data support a key role for cardiolipin in the age-linked decline of rat heart mitochondrial cytochrome c oxidase activity.

Aging↗
PubMed1997

Cardiolipin-dependent decrease of cytochrome c oxidase activity in heart mitochondria from hypothyroid rats.

Cardiolipin plays an important role in mitochondrial membrane structure and function. We have recently reported a decrease in the cytochrome c oxidase activity in heart mitochondria from hypothyroid rats (G. Paradies et al. (1993) Arch. Biochem Biophys. 307, 91-95). A possible involvement of cardiolipin in such a decrease has been proposed. The aim of this work was to test our earlier proposal. We have investigated whether addition of exogenous cardiolipin to hypothyroid mitochondria is able to reverse, in situ, their decreased cytochrome oxidase activity. The method of fusion of liposomes with mitochondria developed by Hackenbrock (Hackenbrock and Chazotte (1986) Methods Enzymol. 125, 35-45) was employed in order to enrich the mitochondrial cardiolipin content. We demonstrate that the decreased activity of this enzyme complex in heart mitochondria from hypothyroid rats can be completely restored to the level of control rats by exogenously added cardiolipin but not by other phospholipids. These data provide strong evidence for the involvement of cardiolipin in the thyroid hormone induced changes of mitochondrial cytochrome oxidase activity.

Animals↗
PubMed1997

Intestinal perforation. A common complication of scleroderma.

The known intestinal complications of systemic sclerosis (SSc) stem mainly from motor disturbances. Autopsy findings were studied to identify anatomic abnormalities that may be associated with this disease. Descriptions of intestinal organs at autopsy were compared in 16 patients with SSc and 18 patients with systemic lupus erythematosus (SLE), a related disease control. There was a high incidence of perforation in SSc (7 of 16 patients) compared to SLE (1 of 18 patients) (P < 0.05). In SSc, perforations involved all parts of the bowel: transmural esophageal fibrosis (after heater probe cautery), dehiscence of suture line after gastric resection, perforated duodenal ulcers (N = 2), terminal ileal ischemia, and diverticulitis (N = 2). Two of the perforations in SSc were silent and were discovered at autopsy. The one perforation in SLE was due to full-thickness necrosis from vasculitis. This study suggests that the intestinal walls of patients with SSc are inherently weak; the gastroenterologist should keep this in mind when performing invasive procedures.

Adult↗
PubMed1996

Stimulation of carnitine acylcarnitine translocase activity in heart mitochondria from hyperthyroid rats.

The effect of hyperthyroidism on fatty acid oxidation and on carnitine-acylcarnitine translocase activity in rat heart mitochondria has been studied. The rates of palmitoylcarnitine supported respiration as well as the carnitine-palmitoylcarnitine exchange reaction were both stimulated (approx. 36%) in heart mitochondria from hyperthyroid rats. Kinetic analysis of the carnitine-carnitine exchange reaction showed that thyroid hormone affects the Vmax of this process, while having no effect on the Km values. The level of cardiolipin was significantly higher (approx. 40%) in heart mitoplasts from hyperthyroid rats than from the control rats. It can be concluded that thyroid hormones produce a stimulation of heart mitochondrial carnitine translocase activity and that the basis of this effect is likely an increase in the cardiolipin content.

Animals↗
PubMed1995

Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-L-carnitine.

Age-related changes in mitochondrial fatty acids metabolism may underlie the progressive decline in cardiac function. The effect of aging and acute treatment with acetyl-L-carnitine on fatty acids oxidation and on carnitine-acylcarnitine translocase activity in rat heart mitochondria was studied. Rates of palmitoylcarnitine supported respiration as well as carnitine-carnitine and carnitine-palmitoylcarnitine exchange reactions were all depressed (approx. 35%) in heart mitochondria from aged rats. These effects were almost completely reversed following treatment of aged rats with acetyl-L-carnitine. Heart mitochondrial cardiolipin content was significantly reduced (approx. 38%) in aged rats. Treatment of aged rats with acetyl-L-carnitine restored the level of cardiolipin to that of young rats. It is suggested that acetyl-L-carnitine is able to reverse age-related decrement in mitochondrial carnitine-acylcarnitine exchange activity by restoring the normal cardiolipin content.

Acetylcarnitine↗
PubMed1995

Graft-versus-host disease after small bowel transplantation is associated with host colonic injury.

The present studies were undertaken to evaluate the histologic effects of graft-versus-host disease on the host colon after small bowel transplantation. Graft-versus-host disease was produced in six Lewis x Brown Norway F1 rats by performing vascularized, out-of-continuity small bowel transplants from parental Lewis donors. Host proximal and distal colon were sampled 14 days after operation when signs of graft-versus-host disease, including weight loss and splenomegaly, were present. Tissue was assessed histologically by blinded observer and compared to eight sham-operated controls. Three histologic features were noted to be statistically increased in diseased animals: (1) mucin loss; (2) crypt abscesses; and (3) large lymphoid aggregates in the mucosa and submucosa. These features were more commonly noted in the distal rather than the proximal colon. Another group of five grafted animals treated with cyclosporine A (10 mg/kg/day intramuscularly) still lost weight but did not display overt signs of graft-versus-host disease and had normal-sized spleens. There was normal mucin content and no evidence of crypt abscesses in these treated animals, although large lymphoid aggregates were present. It is concluded that mucin loss, crypt abscesses, and large lymphoid aggregates are characteristics of graft-versus-host disease-induced colonic injury in this model and that these changes are most evident in the distal colon. Cyclosporine A therapy does not completely reverse the histological changes of colonic graft-versus-host disease. This model may be useful in studying the mechanisms by which immune mediated colitides preferentially affect the distal colon.

Animals↗
PubMed1994

Effect of aging and acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria.

The effect of aging and treatment with acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria was studied. It was found that the activity of both these mitochondrial protein systems was reduced (by around 30%) in aged animals. Treatment of aged rats with acetyl-L-carnitine almost completely reversed this effect. Changes in the mitochondrial cardiolipin content appear to be responsible for these effects of acetyl-L-carnitine.

Acetylcarnitine↗
PubMed1994

Enhanced cytochrome oxidase activity and modification of lipids in heart mitochondria from hyperthyroid rats.

In order to further investigate the mechanism regulating the control of mitochondrial respiration by thyroid hormones, the effect of the hyperthyroidism on the kinetic characteristics of cytochrome c oxidase in rat heart mitochondria was studied. Mitochondrial preparations from both control and hyperthyroid rats had equivalent Km values for cytochrome c, while the maximal activity of cytochrome oxidase was significantly increased (by around 30%) in mitochondrial preparation from hyperthyroid rats. This enhanced activity of cytochrome oxidase was associated to a parallel increase in mitochondrial State 3 respiration. The hormone treatment resulted in a decrease in the flux control coefficient of the oxidase. The enhanced activity of cytochrome oxidase in hyperthyroid rats does not appear to be dependent on an increase in the mass of this enzyme complex in that the heme aa3 content was equivalent in both hyperthyroid and control preparations. The Arrhenius plot characteristics differ for cytochrome oxidase activity in mitochondria from hyperthyroid rats as compared with control rats in that the breakpoint of the biphasic plot is shifted to a lower temperature. Cardiolipin content was significantly increased in mitochondrial preparations from hyperthyroid rats, while there were no significant alterations in the fatty acid composition of cardiolipin of control and hyperthyroid preparations. The results support the conclusion that the enhanced cytochrome oxidase activity in heart mitochondrial preparations from hyperthyroid rats is due to a specific increase in the content of cardiolipin.

Animals↗
PubMed1993

Decreased cytochrome oxidase activity and changes in phospholipids in heart mitochondria from hypothyroid rats.

The effect of hypothyroidism on kinetic characteristics of cytochrome oxidase in rat heart mitochondria was studied. Mitochondrial preparations from control and hypothyroid rats had equivalent Km values for cytochrome c, while the maximal activity of the oxidase was significantly decreased (more than 30%) in mitochondrial preparations from hypothyroid rats. This decrease is associated to a parallel decrease in state 3 respiration. The cytochrome aa3 content was slightly decreased (by around 15%) in mitochondria from hypothyroid rats. The Arrhenius plot characteristics differ for cytochrome oxidase activity in mitochondria from hypothyroid rats as compared with control rats in that the breakpoint of the biphasic plot is shifted to a higher temperature. Cardiolipin content was markedly decreased in the mitochondrial membrane from hypothyroid rats. No alterations were found in the pattern of cardiolipin fatty acid distribution of mitochondrial membrane from control and hypothyroid rats. The effects of the hypothyroid state on the activity of cytochrome oxidase, on cytochrome aa3 levels, and on cardiolipin contents were completely reversed by following the treatment of hypothyroid rats with thyroid hormone. The results support the conclusion that the depressed mitochondrial cytochrome oxidase activity in the hypothyroid state is due, at least in part, to a decrease in the cardiolipin content of the mitochondrial inner membrane.

Animals↗
PubMed1992

The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria.

The effect of aging and treatment with acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria was studied. It was found that the activity of the phosphate carrier was reduced by aging. Treatment of aged rats with acetyl-L-carnitine reversed this effect. The mitochondrial level of cardiolipin was decreased with aging. Treatment of aged rats with acetyl-L-carnitine restored the level of cardiolipin to that of young rats. It is proposed that acetyl-L-carnitine may restore the correct phospholipid composition (cardiolipin level) of the mitochondrial membrane, altered by aging, thereby restoring the activity of the phosphate carrier.

Acetylcarnitine↗
PubMed1992

Helicobacter (Campylobacter) pylori in gastric brushing cytology.

Helicobacter (formerly Campylobacter) pylori is frequently associated with chronic gastritis and peptic ulcer and has been implicated as an etiologic agent. Identification of H. pylori is important for specific treatment with antibiotics and bismuth compounds. We studied 27 patients who presented with symptoms of gastritis or peptic ulcer on whom paired gastric biopsies and gastric brushings for cytology had been performed. Biopsies were stained with H & E and Warthin-Starry or Giemsa for H. pylori. Previously, Papanicolaou-stained brushings were restained with Giemsa and reviewed blindly by two cytologists. Cytologic examination revealed the characteristic 1-3 mu curved or spiral gram-negative bacilli embedded in mucus in 12 of 27 (44%) of cases. Biopsies showed H. pylori in 13 of 27 (48%) of cases. Cytology and histology were concordant in 22 of 27 (81%) of cases. Three cases were positive on biopsy, negative on cytology; two of these were unsatisfactory cytology specimens. Two cases were positive on cytology, negative on biopsy, apparently sampling artifacts. Papanicolaou-stained slides were scored for several morphologic parameters; numbers of acute and chronic inflammatory cells and degree of cytologic atypia. None of these were predictive of the presence of H. pylori. We conclude that Giemsa-stained gastric brushings are a useful complement to gastric biopsies in establishing the diagnosis of H. pylori.

Cytodiagnosis↗