Effects of topical capsaicin combined with moderate exercise on insulin resistance, body weight and oxidative stress in hypoestrogenic obese rats.

BACKGROUND: Hypoestrogenic (HE) women are one of the most vulnerable groups for the development of obesity and its complications. Capsaicin and exercise have demonstrated to reduce body weight and to improve insulin sensitivity in different animal models, but it is unknown whether their combination could be useful in HE obese females. METHODS: We investigated whether topical capsaicin, exercise or their combination had better therapeutic effects in an obesity-hypoestrogenism model. Ovariectomized Wistar rats were given a 30% sucrose solution (HE-Obese (HEOb)) or purified water (HE) during 28 weeks ad libitum; four experimental groups per each condition. After shaving the abdominal skin, cold cream vehicle was applied to the Sedentary groups (Sed) and capsaicin cream 0.075% (0.6 mg kg-1 per day) to the Capsaicin groups (Cap). Exercise (Ex) groups ran on a treadmill every day for 20 min at speeds from 9 to 18 m per min increased every 10 days; combination groups (Cap+Ex) were given topical capsaicin 90 min before exercise. The treatments were performed for 6 weeks, and caloric intake and body weight were monitored. At the end of the experimental protocol, glucose tolerance tests were performed, the animals were killed by decapitation; blood and organs were obtained to perform oxidative profile, histology, biochemical analyses and Western blot. RESULTS: In HEOb rats, the combined therapy reduced caloric intake, body weight and abdominal fat in a higher proportion than the individual treatments; it also decreased insulin resistance (IR), oxidative stress and pancreatic islet size. It was the only treatment that significantly increased p-AMPK levels in the soleus muscle. In HE rats, topical capsaicin was the only treatment that reduced glucose intolerance and improved the oxidative profile in a higher proportion than the combined therapy or Ex alone. CONCLUSIONS: Capsaicin per se or its combination with moderate exercise could be a useful therapy against complications linked to obesity-IR in HE females.

Description of inflammation and cytokine profile at the inoculation site and in heart tissue of mice re-infected with Trypanosoma cruzi vector derived-metacyclic trypomastigotes.

We studied the role of Trypanosoma cruzi reinfection in regard to inflammatory and cytokine response at the inoculation site, lymph node and heart. We reinfected Balb/c mice intradermically into the hind foot-pad with natural infective metacyclic trypomastigotes. They were followed from 24 h to 30 days after the last reinfection. At the inoculation site 24 h after the last re-infection, the infiltrating inflammatory cells increased dramatically with respect to baseline inflammation, reaching maximum infiltrates for the third day. In contrast, parasite DNA was undetectable 24 h after inoculation, despite poor cytokine induction, only IFN-gamma, IL-12 and TGF-beta were noticeable on days 7 and 15, whereas in the lymph nodes draining the inoculation site positive expression of IL-2, IL-4, IL-12 and TGF-beta were found to be induced as soon as 24 h after re-entry of parasite. In the heart, the inflammatory response increased immediately 24 h after re-entry of parasites, reaching its maximum on the 7th day and returning to baseline on day 30. In conclusion, although the inflammatory response is triggered in both compartments by re-entry of parasites, the inflammatory process returns almost to baseline after 30 days, leaving a persistent low-grade inflammation.

Persistence of Trypanosoma cruzi in chronic chagasic cardiopathy patients.

BACKGROUND: Although patients with chronic chagasic cardiopathy do have a strong immune response against Trypanosoma cruzi, they have transient and low parasitemia as well as tissue amastigote nests. When conventional studies were carried out, demonstration of such abnormalities is minimally achieved. Molecular biology may provide the best tools to demonstrate parasite persistence, which could be pathogenic in this progressive disease. METHODS: We studied 16 patients with chronic chagasic cardiopathy (CCC) at the Instituto Nacional de Cardiología Ignacio Chávez in Mexico City. Patients had undergone a complete clinical evaluation, and had antibodies against Trypanosoma cruzi. They came from different rural areas in Mexico. Blood samples were obtained and processed for hemoculture and PCR technique. A CCC necropsy case was also sought for the presence of parasite antigen or DNA, using immunohistochemistry and PCR methods in archival tissues. RESULTS: Five of 16 (31%) hemocultures demonstrated circulating T. cruzi; 60% occurred in persons between 25 and 40 years old. In contrast, we found a positive PCR amplification in 81%; therefore, molecular biology tools appear to be more sensitive for demonstrating parasite persistence. There were no correlations between parasitemic state and clinical findings or specific antibody titer. The autopsy case had parasite antigens and DNA in heart tissues. CONCLUSIONS: Chronic chagasic cardiopathy patients do have persistence of parasite even when parasitemia is low or absent. The continuous presence of a parasite load could maintain immune stimulus and perhaps enhance a pathogenic immune or autoimmune tissue damage in susceptible hosts.

Balance between oxidative damage and proliferative potential in an experimental rat model of CCl4-induced cirrhosis: protective role of adenosine administration.

Oxidative stress and its consequent lipid peroxidation (LP) exert harmful effects, which have been currently involved in the generation of carbon tetrachloride-induced cirrhosis. However, the recent report that "physiological" LP can be associated with liver regeneration (LR) makes it necessary to discriminate between oxidative stress-induced and LR-associated LP. In rats rendered cirrhotic by continuous CCl4 administration for 4 weeks, moderate cell necrosis and fine fatty infiltration were found. The histological abnormalities were accompanied by increased LP, mainly accounted for by the microsomal and cytosolic fractions and evidence of oxidative stress (decreased hepatic glutathione content and changes in xanthine oxidase and pentose phosphate pathway activities). After 8 weeks, a micronodular cirrhosis developed, but oxidative stress was greatly attenuated, only persisting in the enhanced LP confined to microsomes. Simultaneous administration of adenosine, a reliable hepatoprotector that readily prevents the onset of liver fibrosis, was able to block the oxidative stress induced by the long-term CCl4 treatment but elicited a selective subcellular distribution of increased LP, similar to that found during LR. The adenosine-induced changes in liver LP (mainly in the nuclear fraction) correlated with an increased activity of thymidine kinase. Therefore, data suggest that adenosine-mediated preservation of energy availability and mitochondrial function could participate in preventing the onset of oxidative stress in cirrhotic rats. The latter could induce a successful liver recovery, curtailing the sequence of events leading to fibrogenesis.

Sequential changes of energy metabolism and mitochondrial function in myocardial infarction induced by isoproterenol in rats: a long-term and integrative study.

Acute myocardial infarction is the second cause of mortality in most countries, therefore, it is important to know the evolution and sequence of the physiological and biochemical changes involved in this pathology. This study attempts to integrate these changes and to correlate them in a long-term model (96 h) of isoproterenol-induced myocardial cell damage in the rat. We achieved an infarct-like damage in the apex region of the left ventricle, occurring 12-24 h after isoproterenol administration. The lesion was defined by histological criteria, continuous telemetric ECG recordings, and the increase in serum marker enzymes, specific for myocardial damage. A distinction is made among preinfarction, infarction, and postinfarction. Three minutes after drug administration, there was a 60% increase in heart rate and a lowering of blood pressure, resulting possibly in a functional ischemia. Ultrastructural changes and mitochondrial swelling were evident from the first hour of treatment, but functional alterations in isolated mitochondria, such as decreases in oxygen consumption, respiratory quotient, ATP synthesis, and membrane potential, were noticed only 6 h after drug administration and lasted until 72 h later. Mitochondrial proteins decreased after 3 h of treatment, reaching almost a 50% diminution, which was maintained during the whole study. An energy imbalance, reflected by a decrease in energy charge and in the creatine phosphate/creatine ratio, was observed after 30 min of treatment; however, ATP and total adenine nucleotides diminished clearly only after 3 h of treatment. All these alterations reached a maximum at the onset of infarction and were accompanied by damage to the myocardial function, drastically decreasing left ventricular pressure and shortening the atrioventricular interval. During postinfarction, a partial recovery of energy charge, creatine phosphate/creatine ratio, membrane potential, and myocardial function occurred, but not of mitochondrial oxygen consumption, rate of ATP synthesis, total adenine nucleotides, or mitochondrial proteins. Interesting correlations of the sequential changes in heart and mitochondrial functions with energy metabolism were obtained at different stages of the isoproterenol-induced cardiotoxicity. These correlations could be useful to study and understand the cellular events involved in this pathology.

Sucrose administration to partially hepatectomized rats: a possible model to study ethanol-induced inhibition of liver regeneration.

Although acute ethanol treatment drastically inhibits liver regeneration after partial hepatectomy, the exact mechanisms involved remain obscure. On the other hand, it is known that early carbohydrate administration promotes a more successful restoration of the liver mass. Therefore, carbohydrate administration could be an experimental approach for studying ethanol action on the regenerating liver. In rats subjected to two-thirds partial hepatectomy, ethanol was administered alone or in combination with a variety of carbohydrates (glucose, fructose, glucose plus fructose, sucrose and maltose). In liver samples, regeneration parameters and histological assessment were performed. Blood ethanol and metabolites reflecting liver function were assayed. Ethanol intake strongly decreased the incorporation of [3H]thymidine into liver DNA, the concentration of DNA/g of tissue, and thymidine kinase activity. In this group, severe alterations in cell structure (i.e. abundant fat droplets and abnormal mitochondria) were found. Carbohydrates readily improved the survival rate of ethanol-intoxicated hepatectomized rats. Sucrose was effective in reverting the ethanol-induced alterations in liver structure and the parameters of liver regeneration, and partially blocked the ethanol-induced alterations in serum levels of albumin, triacylglycerols and ammonia without modifying the blood levels and clearance of ethanol. Data suggest that the beneficial action of sucrose might be related to an adequate supply of energetic sources at early times of liver regeneration, rather than altering ethanol bioavailability. Thus, the present model could be an experimental approach for studying the metabolic alterations involved in the ethanol-induced inhibition of the liver regeneration.

American trypanosomosis: in situ and generalized features of parasitism and inflammation kinetics in a murine model.

American trypanosomiasis: In situ and generalized features of parasitism and inflammation kinetics in a murine model. Experimental Parasitology 83, 267-274. Mimicking the natural conditions of mammalian infection, metacyclic trypomastigote forms of a Mexican isolate (Ninoa) of Trypanosoma cruzi were inoculated into mice in order to study inflammation kinetics and parasite clearance at the inoculation site, parasite tropism to different organs, and local inflammatory cell infiltrates. Polymorphonuclear cells were detected at the inoculation site as early as 1 hr after inoculation. Peak cell infiltrate was observed at 24 hr; at 96 hr polymorphonuclear cells had disappeared. Mononuclear cell infiltrates began at 24 hr, peaking at Day 15, and then stared disappearing by Day 30. Antigens and parasites were detected by conventional techniques up to 15 min and thereafter became undetectable. Amplification of the hypervariable region of kinetoplast minicircle DNA by polymerase chain reaction was positive from 24 hr to Day 15, and the reaction became negative on Day 30. Myositis was observed in skeletal muscle from Days 7 to 180, it progressed from slight to severe, with an inflammation process which included macrophages, plasmatic cells, and a few eosinophils, the phenotype of the infiltrating cells included LyT2+ and LyT1+ on Day 30, and both cell populations decreased in parallel on Day 180. Antigen and parasite nests were present from Day 15 to 180; in muscle the earliest time at which minicircle DNA was detected was Day 7 and it was present until Day 180. Myocarditis was also observed; it developed from slight to severe in between Days 7 and 30, then gradually decreased, and cleared up. Mononuclear cell infiltrates in the myocardium were present from Days 7 to 180. Antigen and parasite nests were detected at Days 15 and 30 and disappeared at Day 180, although minicircle DNA was detected until the last day of observation. Both skeletal and heart muscles showed inflammatory reaction foci containing T. cruzi antigen. There was twice the number of foci in heart as in skeletal muscle. This ratio was maintained by Day 30; later skeletal muscle showed persistent inflammation which was practically cleared up in the heart. Parasites or antigen were not detected by Day 180 in both skeletal and cardiac muscle; however, minicircle DNA was amplified, indicating that an small proportion of parasites evaded immune response. According to these data, Mexican Ninoa Strain has a classification as biodeme 3.

[Reconstruction of the normal right ventricle outflow tract in the Ross operation]. / Reconstrucción del tracto de salida normal del ventrículo derecho en la operación de Ross.

Now a day there are many surgical procedures that require intervention on the normal right ventricular outflow tract (RVOT) and its reconstruction. We present the surgical anatomy of the pulmonary root in the normal RVOT and its reconstruction in the Ross operation in 13 patients operated on from February 1992 through February 1994. The surgical excision of the pulmonary valve was done and in order to keep right ventricle-pulmonary artery continuity (RV-PA), autologous pericardium tubes with bovine pericardium valve [done at the Instituto Nacional de Cardiología (INC)], were elaborated during the surgical procedure in all patients. The postoperative period and its clinical status was satisfactory in all cases, without transpulmonary gradient or regurgitation. We conclude that is important to know the surgical anatomy of the pulmonary root in order to avoid irreversible damage. In the other hand, it is worthy to know the different choices to reconstruct RVOT and its postoperative clinical course.