The aging process in prison: pathologies and health conditions in old inmates. An epidemiological research in Italy.

BACKGROUND AND AIMS: Elderly may suffer from different pathologies during their detention in jail because of their age. Conditions in jails were tough and adapting to that life could be problematic for the elder population. This article aimed to analyse the pathologies and health conditions in a sample of elder inmates from Italy. METHODS: The sample was composed by 94 elderly inmates. The research is multicentric. We selected jails from the cities of Bari, Taranto, Foggia, Lecce, Brescia, Bergamo, Cremona and Mantua. The study was conducted by interviewing the prisoners over 60 years of age, in the period between September and December 2017. RESULTS: 64% of the sample was in a "Not Optimal" health status. Most of pathologies were Cardiac pathologies (23.4%), Diabetes (12.8 %) and Surgery (9.6%). Statistically significant differences were found for heart disease (p=0.02) and Neoplasia (p=0.025) in the prison of Bari compared to all the other prisons. Statistically significant differences were found for Hypertension in Foggia and Taranto prisons compared to all the other (p=0.023). Furthermore, 18.1% of inmates ended up having an addiction. CONCLUSIONS: Our analysis showed that in our sample physical problems were more frequent than psychological one. In fact, in spite of in the literature there was a high prevalence of mental health problems among elderly inmates, we did not find this result. However, stress conditions may increase the risk of pathologies: for example, being in jail and adapt to new hard environment may increase the risk of getting sick. Heart disease pathologies and diabetes were very common in our sample as confirmed by the literature.

Novel therapeutics for the treatment of familial Mediterranean fever: from colchicine to biologics.

Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is characterized by sporadic, paroxysmal attacks of fever and serosal inflammation, lasting 1-3 days. Patients may develop renal amyloidosis, arthritis, serositis, and skin and oral lesions. Diagnosis is based on clinical features, response to treatment with colchicine, and genetic analysis. Colchicine prevents attacks and renal amyloidosis, in addition to reversing proteinuria. Nonresponders may receive novel therapy, including interleukin (IL)-1 receptor antagonists and IL-1 decoy receptor. Recently, new options have been considered.

Re-wiring the circuit: mitochondria as a pharmacological target in liver disease.

Mitochondria play a key role in intracellular energy-generating processes, cell life and death, and are heavily involved in several metabolic pathways by integrating signaling networks; thus, a very large number of conditions are characterized by mitochondrial bioenergetic in humans. Often, mitochondrial changes are directly or indirectly dependent on the activation of intracellular stress cascades or death receptor-mediated pathways. Reactive oxygen species (ROS) formation, glutathione (GSH) depletion, protein alkylation and respiratory complex alterations are major events associated with mitochondrial dysfunction and represent critical initiating events in most forms of chronic liver disease. Through creating an analogy with a disrupted electric circuit gone bad, the present review focuses initially on how hepatic mitochondrial bioenergetics is affected in the context of drug and disease-induced liver failure and how targeting mitochondria with several antioxidant agents can be helpful for preventing the disruption of the mitochondrial electric circuit.

Antagonism of the cannabinoid CB-1 receptor protects rat liver against ischaemia-reperfusion injury complicated by endotoxaemia.

BACKGROUND/AIM: Endotoxaemia can complicate hepatic ischaemia-reperfusion (IR) injury. Endocannabinoids appear to modulate the haemodynamic alterations and cytokine response induced by lipopolysaccharide (LPS). Thus, we aimed to determine the effect of the endocannabinoid CB1-receptor antagonist Rimonabant in a model of hepatic IR injury complicated by endotoxaemia. METHODS: Sprague-Dawley rats pre-treated with Rimonabant 3 or 10 mg/kg or vehicle underwent partial hepatic IR and lipopolysaccharide (LPS) injection at reperfusion. Liver injury was evaluated by serum alanine aminotransferase (ALT) and necrotic-cell count. The inflammatory response was investigated by assessing hepatic neutrophil infiltration, tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), interleukin 6 (IL6), and suppressor of cytokine signalling (SOCS) 1 and SOCS3 gene expression by real-time polymerase chain reaction (RT-PCR). Systolic blood pressure and hepatic blood flow were measured as haemodynamic parameters. Finally, lipid peroxidation, glutathione status, and immunoreactive CB1 receptor expression in the liver were also determined. RESULTS: Liver injury and neutrophil infiltration occurring in the late-phase of LPS-enhanced IR were significantly reduced by CB1-receptor antagonism. Rimonabant-treated rats showed significantly higher gene expression of IFNgamma, IL6, SOCS1 and SOCS3 in "early" reperfusion, while that of TNFalpha was reduced. These findings were associated with increased STAT3 phosphorylation. Furthermore, CB1-receptor antagonism significantly improved the oxidative injury and haemodynamic alterations occurring during reperfusion in untreated rats. Finally, CB1-receptor immunoreactivity was upregulated early after reperfusion. CONCLUSIONS: This study demonstrates that CB1-receptor antagonism protects the liver against LPS-enhanced IR injury by interfering with the inflammatory response that causes the late, neutrophil-dependent phase of reperfusion injury, although the prevention of the transient endotoxin-related hypotension occurring early during reperfusion may be also involved.

Oxidative injury in rat fatty liver exposed to ischemia-reperfusion is modulated by nutritional status.

BACKGROUND AND AIMS: Oxidative stress contributes to ischemia-reperfusion injury in fatty livers. This study aimed to determine whether glycogen depletion influences this oxidative injury and whether the administration of glucose can be protective. METHODS: Rats with choline deficiency-induced fatty liver underwent hepatic ischemia-reperfusion. Experimental groups: (1) fed rats; (2) 18 h fasted rats; (3) 18 h fasted rats supplemented with glucose prior to surgery. The thiobarbituric acid-reactive substances, protein carbonyls and total glutathione concentrations were measured in liver tissue and isolated mitochondria as parameters of oxidative stress before and after ischemia and during reperfusion. The mitochondrial F1-ATPase content and the serum alanine transaminase were also determined. RESULTS: With respect to fed rats, fasted rats exhibited an increased oxidative injury in both liver tissue and isolated mitochondria throughout the experiment with the only exception of thiobarbituric acid-reactive substances, which were not affected by the nutritional status in liver tissue. Fasted rats showed a significantly lower F1-ATPase content and higher alanine transaminase levels. Glucose supplementation significantly reduced the fasting-associated exacerbation of oxidative stress and liver injury and the F1-ATPase exhaustion. CONCLUSIONS: These data indicate that the pre-existing hepatic glycogen content modulates the oxidative damage in rat fatty livers exposed to ischemia-reperfusion injury and that the energetic substrate supplementation may represent a clinically feasible protective strategy.

Modulation of endometrial redox balance during the menstrual cycle: relation with sex hormones.

This study aimed to evaluate the effects of changes in sex hormones occurring during the menstrual cycle on the redox balance and lipid peroxidation in normal human endometrial cells. Forty women, ages 21-41 yr, who were admitted to the Department of Gynecology and Obstetrics of the University of Bari for routine checkups or were treated for benign uterine disease, underwent endometrial biopsy and venipuncture. On the basis of histological examination, patients were allocated as follows: 10 in the early proliferative phase, 12 in the late proliferative phase, 8 in the early secretory phase, and 10 in the late secretory phase. LH, FSH (immunoradiometric essay), estradiol (E2), and progesterone (P(4)) (RIA) were determined in plasma samples. On the endometrial specimens, total glutathione (GSH), oxidized GSH (GSSG), malondialdehyde, and GSH peroxidase activity (GSH-Px) were determined. Significant cycle-dependent changes in endometrial GSH-Px (P < 0.0001), GSH (P < 0.001), and GSSG as a percentage of GSH (P < 0.0001) were observed. Malondialdehyde did not show significant differences. A linear regression model correlating sex hormone changes with redox indexes was performed. A significant positive correlation was observed between E2 and GSH-Px (r = 0.74; P = 0.0001), E2 and GSSG, as percentage of total (r = 0.84; P < 0.0001); a negative correlation was found between E2 and GSH (r = -0.57; P = 0.0001). No significant correlation was found between P(4) or FSH and oxidative balance. LH was found to be correlated with GSH-Px (r = 0.66; P = 0.0001) and GSSG as percentage of GSH (r = 0.5; P < 0.001). We conclude that the hormonal pattern is involved in maintaining the optimal redox balance in endometrium, mainly through modulation of GSH level and metabolism.

Mitochondrial oxidative damage and myocardial fibrosis in rats chronically intoxicated with moderate doses of ethanol.

Mitochondrial oxidative balance and myocardial fibrosis were investigated in pair-fed rats received ethanol (3%) or saccharose in drinking water for 8 weeks. The concentrations of glutathione, malondialdehyde, protein carbonyls and sulfhydrils were determined. The presence and distribution of fibronectin were detected by immunohistochemistry. The myocardial concentrations of reduced glutathione and protein sulfhydrils were lower in ethanol treated rats. The oxidised/reduced glutathione ratio, the levels of malondialdehyde and protein carbonyls were higher in ethanol-treated rats. The mitochondrial amount of proteins, glutathione and protein sulfhydrils were lower in ethanol treated rats, whereas the content of protein carbonyls and malondialdehyde were higher. Accumulation of fibronectin was detected at subepicardial and subendocardial districts in ethanol-treated rats, with moderate degree of fibrosis in 20% of the cases. In conclusion, moderate ethanol consumption is associated with oxidative damage to heart mitochondria and fibronectin deposition. These oxidative and ultrastuctural changes may be assumed as basic alterations in the development of alcoholic cardiomyopathy.

Increased oxidative stress in dimethylnitrosamine-induced liver fibrosis in the rat: effect of N-acetylcysteine and interferon-alpha.

Oxidative stress may represent a common link between chronic liver damage and hepatic fibrosis. Antioxidants and interferon seem to protect against hepatic stellate cell (HSC) activation and liver fibrosis. This study evaluated (1) the effect of the profibrotic agent dimethylnitrosamine (DMN) on the hepatic oxidative balance in the rat; (2) the role played by the antioxidant agent N-acetylcysteine (NAC); and (3) the antifibrotic effects of two different types of interferon-alpha: recombinant alpha-2b (rIFN-alpha) and leukocyte alpha (LeIFN-alpha). Five groups of rats received: (1) saline; (2) DMN; (3) DMN + NAC; (4) DMN + rIFN-alpha; and (5) DMN + LeIFN-alpha. Oxidative balance was evaluated by hepatic glutathione, TBARs, protein carbonyl, and sulfhydryl determination. Fibrosis was determined by hepatic hydroxyproline content and fibronectin (FN) staining (immunohistochemistry). DMN rats showed a diffuse FN deposition, an impaired oxidative balance, and higher hepatic hydroxyproline levels compared to that of controls. NAC administration significantly reduced FN deposition, increased hepatic glutathione, and decreased TBARs and protein carbonyls. Administration of IFN-alpha exerted different effects according to the type used. Both IFNs decreased FN deposition; however, LeIFN-alpha significantly improved histology and oxidative parameters compared to those of untreated DMN and rats treated with rIFN-alpha. This study shows the role of free radicals in this model of hepatic fibrosis; the protective effect of NAC against liver fibrosis; and the antifibrotic effect exerted by IFN-alpha (particularly LeIFN-alpha) independent of its antiviral activity.

Increased generation of reactive oxygen species in isolated rat fatty liver during postischemic reoxygenation.

BACKGROUND: Whether fatty infiltration of the liver influences the generation of reactive oxygen species (ROS) during reperfusion is unclear. Thus, this study aimed to compare the ROS formation that occurs during postanoxic reoxygenation in isolated normal and fatty livers. METHODS: Isolated livers from fed Sprague-Dawley rats with normal or fatty livers induced by a choline-deficient diet were reperfused at 37 degrees C for 60 min with an oxygenated medium containing 10 microM of lucigenin after 1 hr of warm ischemia. Superoxide anion generation was assessed by the chemiluminescence (CLS) signal emitted from the organ surface. The hepatic content of malondialdehyde (MDA) and glutathione was determined at the end of reperfusion. Tissue injury was evaluated by the liver histology and the alanine aminotransferase (ALT) release in the perfusate. RESULTS: CLS started rapidly with reoxygenation and it diffused to the whole organ in both groups. However, CLS emission was significantly higher in fatty liver (after 10 min: 812.425+/-39.898 vs. 294.525+/-21.068 photons/cm2/sec; P<0.01). A greater concentration of MDA was measured at the end of reoxygenation in fatty liver. Finally, the liver histology and the ALT release indicated a greater injury in steatotic than normal liver. CONCLUSIONS: The CLS technique allows a direct visualization and comparison of ROS generation from the organ surface. Fatty infiltration increases ROS generation in the liver during postischemic reoxygenation, likely leading to the greater lipid peroxidation observed in these experiments. The increased oxidative stress may contribute to the reduced tolerance of steatotic livers to ischemia-reperfusion injury.

Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: effect of the nutritional status.

Hepatic steatosis is associated with mitochondrial oxidative alterations. This study aimed to characterize in a choline-deficient model of rat fatty liver whether this oxidative imbalance is related to an impairment of the capacity of ATP synthesis both under fed conditions and after starvation, which may sensitize mitochondria to oxidative injury. Mitochondria were isolated from normal and fatty livers of fed or 18-hour fasted rats. Oxidative injury was evaluated by measuring the mitochondrial content of thiobarbituric reactive substances, protein carbonyls, glutathione, and protein sulfhydryls. The mitochondrial F(0)F(1)-ATP synthase content, tissue ATP concentration, and liver histology were also determined. Compared with normal liver, under fed conditions, fatty livers showed a greater mitochondrial content of oxidized lipids and proteins together with a low concentration of sulfhydryls and glutathione. The mitochondrial catalytic beta-F(1) subunit of the F(0)F(1)-ATP synthase was about 35% lower in fatty livers. Hepatic ATP was also significantly reduced in fatty liver. Starvation exacerbated mitochondrial oxidative injury in both groups but to a greater extent in fatty livers. In the steatotic group, fasting induced a significant decrease of the ATP levels, which was accompanied by a 70% fall of the catalytic beta-F(1) subunit. These data indicate that the mitochondrial oxidative alterations in fatty livers are associated with an important reduction of the F(0)F(1)-ATP synthase. These changes, which are greatly exacerbated after starvation, may account for the reduced synthesis of the hepatic ATP observed in the presence of fatty infiltration.

Food deprivation exacerbates mitochondrial oxidative stress in rat liver exposed to ischemia-reperfusion injury.

Mitochondria undergo oxidative damage during reperfusion of ischemic liver. Although nutritional status affects ischemia-reperfusion injury in the liver, its effect on mitochondrial damage has not been evaluated. Thus, this study was designed to determine whether starvation influences the oxidative balance in mitochondria isolated from livers exposed to warm ischemia-reperfusion. Fed and 18- and 36-h food-deprived rats underwent partial hepatic ischemia followed by reperfusion. Mitochondria were isolated before and after ischemia and during reperfusion. Serum alanine transaminase was measured to assess liver injury. The mitochondrial concentrations of malondialdehyde, protein carbonyls and glutathione were determined as indicators of oxidative injury. Cell ultrastructure was assessed by transmission electron microscopy. Transaminase levels were greater in 18-h food-deprived than fed rats (after 120 min of reperfusion: 3872 +/- 400 vs. 1138 +/- 59 U/L, P < 0.01). Mitochondrial glutathione was lower in food-deprived than fed rats before and after ischemia, and during reperfusion. Food deprivation also was associated with significantly greater lipid and protein oxidative damage. Finally, more ultrastructural damage was observed during reperfusion in mitochondria from food-deprived rats. Prolonging the length of food deprivation to 36 h exacerbated significantly both the mitochondrial oxidative injury and the release of serum transaminases in rats (after 120 min of reperfusion: 5438 +/- 504 U/L, P < 0.01). Food deprivation was associated with greater mitochondrial oxidative injury in rat livers exposed to warm ischemia-reperfusion, and the extent of oxidative damage in mitochondria increased with the length of food deprivation.

Oxidative stress in symptom-free HCV carriers: relation with ALT flare-up.

BACKGROUND: The reason why some hepatitis C virus carriers with normal aminotransferase activity present, during time, an activation of the disease, is unknown. The aim of this study was to assess the oxidative balance in such patients and to evaluate its possible role on the severity of disease. MATERIALS AND METHODS: Histology, glutathione and malondialdehyde were determined in the liver of 30 HCV-RNA positive patients with persistently normal aminotransferase. Patients were followed-up for 18 months with plasmatic determinations of aminotransferase, ferritin, glutathione, malondialdehyde, carbonyl and sulphydryl protein levels (every 2 months) and serum HCV-RNA (every 3 months). RESULTS: Four subjects had normal histology, whereas the remaining 26 showed mild/moderate chronic hepatitis. Hepatic glutathione and malondialdehyde concentrations were normal in 16 patients and clearly altered in the other 14. The hepatic redox state did not correlate with histology whereas it correlated with plasmatic oxidative markers. During the study, aminotransferase flared up in 11 patients, 9 of these (82%) having at enrollment an altered hepatic oxidative balance. Patients with aminotransferase elevation showed increased blood indices of oxidative stress, which occurred earlier than aminotransferase flare-ups. No oxidative stress was observed in the remaining subjects. DISCUSSION: This study suggests that symptom-free HCV carriers with impaired redox state have a higher risk of aminotransferase flare-up; therefore the impaired oxidative balance may have a prognostic significance on disease activity.

Starvation impairs antioxidant defense in fatty livers of rats fed a choline-deficient diet.

Although fatty liver (FL) is considered an innocuous condition, the frequent incidence of graft failure when FL are transplanted has renewed interest in the intracellular disorders causative of or consequent to fatty degeneration. Oxidative stress and nutritional status modulate the tolerance to reperfusion injury in control livers (CL), but very little is known in the case of FL. This study was designed to compare the oxidative balance in CL and FL from fed and food-deprived rats. Serum and liver samples were collected from fed and starved (18 h) rats with CL or FL induced by a choline-deficient diet. Hepatic injury was assessed by transaminase activities and histology. The hepatic concentrations of glutathione (GSH), vitamin C, alpha-tocopherol, thiobarbituric acid-reactive substances (TBARS) and protein carbonyls (PC) were measured. Fed rats with FL had significantly greater TBARS and lower alpha-tocopherol and vitamin C levels than those with CL, whereas GSH and PC concentrations were not affected. Starvation impaired the oxidative balance in both groups. However, compared with the other groups, FL from food-deprived rats generally had the lowest hepatic concentrations of alpha-tocopherol, vitamin C and GSH. Unlike in CL, protein oxidation occurred in FL. These data indicate that fatty liver induced by consumption of a choline-deficient diet is associated with a lower level of antioxidants, which results in lipid peroxidation. Starvation further affects these alterations and extends the damage to proteins. In conclusion, steatosis and starvation may act synergistically on the depletion of antioxidants, predisposing fatty livers to a reduced tolerance to oxidative injury.

Effect of oral and intravenous S,N-diacetylcysteine monoethyl ester on circulating and hepatic sulfhydryls in the Rat.

The role of GSH in the detoxification of reactive metabolites of oxygen and xenobiotics, in gene expression, and as a source of cysteine is well established. Because decreased circulating and intracellular concentrations of GSH might be of pathogenetic relevance in several clinical conditions, there is a growing interest in pharmacological interventions to correct a deranged sulfhydryl status. In this study, the disposition and the effect of S,N-diacetylcysteine monoethyl ester (DACE) on sulfhydryls were investigated after i.v. and intraduodenal (i.d.) administrations to rats. DACE was rapidly hydrolyzed and deacetylated to N-acetylcysteine and cysteine in plasma. High concentrations of cysteine were attained in the circulation and in the liver after i.v. and i.d. administrations of 5 mmol/kg DACE, and physiological levels of GSH in the liver and in plasma increased by 30 and 300%, respectively, with i.v. and i.d. administrations. Incubation of peripheral blood mononuclear cells with 1 mM DACE resulted in higher intracellular concentrations of cysteine and GSH after 24 h than incubations with equimolar concentrations of cysteine, N-acetylcysteine, or oxothiazolidine carboxylic acid, respectively. It is concluded that DACE provides an efficient delivery system for cysteine that markedly increases intra- and extracellular cysteine and GSH after i.v. and i.d. administrations. Because its uptake into cells is probably not dependent on an active transport process, DACE results in higher intracellular concentrations of cysteine than those resulting from other prodrugs of cysteine and cysteine itself. The compound may thus have advantages over other compounds for the correction of a deranged sulfhydryl status.

Chronic ethanol administration induces oxidative alterations and functional impairment of pancreatic mitochondria in the rat.

Pancreas is known to be vulnerable to ethanol (ETOH) at high doses, but little is known about the effect of lower doses. Therefore, in this study, the levels of glutathione (GSH), sulfhydryl proteins (P-SH), carbonyl proteins, malondialdehyde (MDA), and adenosine triphosphate (ATP) production were determined in the pancreatic tissue and mitochondria of rats fed for 8 weeks with 3% ETOH. ETOH decreased the pancreatic pool of ATP, while GSH and P-SH also decreased in mitochondria. MDA concentrations increased both in the pancreas and mitochondria, while carbonyl proteins increased only in mitochondria. Pancreatic cells of ETOH-treated rats were frequently affected by cytoplasmic vacuolization and swelling; these alterations were often associated with ductular dilatation. In conclusion, ETOH produces oxidative and morphologic alterations in the pancreas of the rat, including impairment of mitochondria. These effects may represent basic mechanisms of ETOH-induced pancreatic injury.

An update on the role of free radicals and antioxidant defense in human disease.

Mounting clinical and experimental evidence indicates that free radicals play important roles in many physiological and pathological conditions. The wider application of free radical measurement has increased awareness of functional implications of radical-induced impairment of the oxidative/antioxidative balance. In the following review, the role of oxygen free radicals in some human and experimental pathological conditions is described, with particular emphasis on the mechanisms by which they produce oxidative damage to lipids, proteins, and nucleic bases. The role of free radicals and the activation of the antioxidant systems in arteriosclerosis and ageing, diabetes, ischemia/reperfusion injury, ethanol intoxication, and liver steatosis is discussed. Therapeutic approaches to the use of antioxidants have been described and prospects for clinical use have been considered.

Reperfusion injury of the liver: role of mitochondria and protection by glutathione ester.

BACKGROUND: Reperfusion injury of the liver is characterized by intravascular oxidative stress and GSH consumption. Whether mitochondria contribute to hepatocellular damage has never been elucidated. Therefore, we assessed mitochondrial function and redox state during reperfusion and the effect of glutathione monoethyl ester (GSHE) administration, which may replenish the GSH pool. MATERIALS AND METHODS: Rats were subjected to partial hepatic ischemia (90 min) followed by reperfusion. Mitochondrial function was assessed in vivo and in vitro by the KICA breath test and the ATP synthase activity. Just prior to the start of reperfusion, rats received 5 mmol/kg of GSHE or saline iv. ALT, total and oxidized (GSSG) glutathione, GSHE, and CYS were measured in plasma and liver. GSH, GSSG, malondialdehyde (MDA), and carbonyl proteins were measured in mitochondria. The extent of necrosis was also estimated. Sham-operated rats served as controls. RESULTS: Reperfusion markedly increased ALT (>1500 U/L) and doubled the liver content of MDA and carbonyl proteins. Mitochondrial GSH decreased approximately 30%, without increase of GSSG. The in vivo KICA breath test was not significantly impaired by reperfusion. In contrast, both KICA decarboxylation and ATP synthase activity were both reduced by approximately 50% in mitochondria isolated from reperfused livers. GSHE administration significantly decreased ALT ( approximately 40%), protected ATP synthase activity, and reduced the extent of necrosis. Compared to controls, plasma GSHE and plasma GSH at 1 h were lower in rats subjected to ischemia. GSHE was higher in reperfused lobes than in continuously perfused ones and the concentration of GSH was significantly higher in ischemic liver than in untreated animals, indicating that the uptake of GSHE is increased in postischemic liver. GSHE prevented the reperfusion-associated increase of oxidized products in liver and mitochondria. CONCLUSIONS: Reperfusion of ischemic liver is associated with oxidative modifications and functional impairment of mitochondria. GSHE protects against reperfusion injury, possibly by providing intra- and extracellular GSH.

Mitochondrial oxidative alterations following partial hepatectomy.

Mitochondria, isolated from rat livers during the early phase of liver regeneration (7-24 h after partial hepatectomy), show: (i) decrease in the rate of ATP synthesis; (ii) increase of malondialdehyde and of oxidized protein production; (iii) decrease of the content of intramitochondrial glutathione and of protein thiols on mitochondrial proteins; (iv) increase of the glutathione bound to mitochondrial proteins by disulfide bonds. These observations suggest an increase of production of oxygen radicals in liver mitochondria, following partial hepatectomy, which can alter the function of the enzymes involved in the oxidative phosphorylation. Blue-native gel electrophoresis of rat liver mitochondria, isolated after partial hepatectomy, shows, during the early phase of liver regeneration (0-24 h after partial hepatectomy), a progressive decrease of the content of F0F1-ATP synthase complex. The amount of glutathione bound to the F0F1-ATP synthase, electroeluted from the blue-native gels, progressively increased during the early phase of liver regeneration. It is concluded that partial hepatectomy causes mitochondrial oxidative stress that, in turn, modifies proteins (such as F0F1-ATP synthase) involved in the mitochondrial oxidative phosphorylation.

Oxidative retinal products and ocular damages in diabetic patients.

Several evidences suggest a retinal participation to the genesis of diabetic eye complications by means of an increased free radical production at this level. However, no direct proof exists that this happens in humans in vivo. Therefore, the concentrations of malondialdehyde (MDA), carbonyl and sulfhydryl (P-SH) proteins, and vitamin E have been assessed in the subretinal fluid (SF) of patients affected by retinal detachment. Diabetic (n = 19) and nondiabetic (n = 21 ) subjects with comparable age, degree of myopia, and duration of the retinal detachment were considered. A control group of n = 7 subjects was included. The SF was collected after drainage during surgery. The concentrations of total proteins, P-SH, and carbonyl proteins were determined with spectrophotometric methods; the levels of MDA and vitamin E were measured by HPLC. The protein concentration in SF did not differ among groups. A higher concentration of MDA (p < .01) and carbonyl proteins (p < .02) were found in diabetic compared to nondiabetic subjects. Diabetic patients also showed a lower content of P-SH (p < .002) and vitamin E (p < .001) compared to nondiabetic subjects. All these parameters were more markedly altered in patients affected by proliferative diabetic retinopathy and significantly differed between patients and control subjects. In conclusion, oxidative events are associated with retinal detachment in humans. This evidence strongly suggests that the retina is a source of free radical production under certain conditions, such as diabetes.