Resveratrol reverses diabetes-related decrement in sildenafil-induced relaxation of corpus cavernosum in aged rats.

BACKGROUND: The aim of this study was to investigate the effect of resveratrol (RVT) on sildenafil-induced relaxations of isolated corpus cavernosum in non-diabetic and diabetic aged rats. METHODS: A total of 13 male aged rats (72-80 weeks old) were randomized into two groups including non-diabetic aged rats and diabetic aged rats. Diabetes was induced in aged rats by streptozotocin (single i.p. dose of 45 mg/kg body weight) administration. At the end of the 12th week, corpus cavernosum strips of rats were suspended in an organ bath system. The corpus cavernosum relaxation was evaluated by sildenafil in the presence or absence of RVT (10-4 M) for 45 min. RESULTS: Induction of diabetes resulted in significant inhibition of sildenafil-induced corpus cavernosum relaxation in aged rats. The diminished relaxation in response to sildenafil was significantly improved by acute RVT incubation in both non-diabetic and diabetic aged rats; however, the magnitude of potentiation induced by RVT was more pronounced in diabetic aged rats. The potentiating effect of RVT was significantly inhibited by L-NG-nitroarginine methyl ester (L-NAME, 10-4 M, for 30 min) incubation in both groups. After the L-NAME incubation, the relaxation response of corporal tissues evoked by sildenafil was found to be similar in diabetic and non-diabetic aged rats. CONCLUSIONS: RVT improves sildenafil-induced relaxations of corpus cavernosum in both diabetic and non-diabetic aged rats probably by potentiating the activity of NOS, and this effect seems to be more manifest in diabetic aged group.

Differential activation and expression of insulin receptor substrate 1 (IRS1) in mononuclear cells of type 2 diabetes patients after insulin stimulation.

Insulin regulates the glucose homeostasis by inducing tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. IRS1 is the best studied member of this family and insulin-induced Tyrosine phosphorylation of (YXXM) motifs provides docking site for SH2 domain-containing proteins. Recent studies have suggested that genetic and/or environmental factors may affect the expression and phosphorylation levels of IRS1, and these could be important for development of insulin resistance. To shed light to the molecular basis of type 2 diabetes we wanted to determine whether YXXM motifs are genetically modified in these patients. We have isolated mononuclear cells of eighteen type 2 diabetes patients and prepared genomic DNA and protein lysates from these cells. The genomic DNA was used to sequence IRS1 gene, and protein lysates were used to determine the expression and phosphotyrosine levels of IRS1 after insulin stimulation. Although, we did not detect any mutations at/or near the YXXM coding regions in patients' DNA, immunprecipitation analysis of IRS1 indicated decreased levels of expression and tyrosine phosphorylation of IRS1 in patient's samples compared to that of healthy controls. Our results suggest that mononuclear cells of patients can be used to test the levels of insulin responsiveness before therapy.

SERUM 25-HYDROXYVITAMIN D(3) LEVELS IN TYPE 2 DIABETIC PATIENTS WITH NORMO-, MICRO-, AND MACROALBUMINURIA.

BACKGROUND: The aim of this study was to observe the differences in serum 25-hydroxyvitamin D(3) levels in nondiabetic healthy control subject and type 2 diabetic patients, and to investigate the differences in serum 25-hydroxyvitamin D(3) levels in type 2 diabetic patients with normo-, micro- and macroalbuminuria. PATIENTS AND METHODS: Total 140 nondiabetic healthy controls and 384 type 2 diabetic patients (156 normoalbuminuric, 152 microalbuminuric and 76 macroalbuminuric) were included in the study. 25-hydroxyvitamin D(3) levels were measured in sera with the method of electrochemiluminescence using modular immunoassay analyzer. RESULTS: Vitamin D deficiency was detected in 70.85% and 22.9% of type 2 diabetic patients and nondiabetic healthy controls, respectively. Serum 25-hydroxyvitamin D(3) levels were significantly lower in type 2 diabetic patients compared to nondiabetic healthy controls (16.4 ± 9.5 ng/mL vs. 28.2 ± 11.6 ng/mL, p=0.0001). Serum 25-hydroxyvitamin D(3) levels were lower in albuminuric and nonalbuminuric diabetic patients (14.3 ± 7.9 ng/mL vs. 19.6±10.9 ng/mL, respectively, p=0.013). Serum 25-hydroxyvitamin D(3) levels were 19.6 ± 10.9 ng/mL in normoalbuminuric, 14.9 ± 8.8 ng/mL in microalbuminuric and 12.9 ± 5.8 ng/mL in macroalbuminuric diabetic patients. While lower serum 25-hydroxyvitamin D(3) levels were detected both in microalbuminuric (p=0.028) and macroalbuminuric diabetic patients (p=0.014) compared to normoalbuminuric diabetic patients, 25-hydroxyvitamin D(3) levels did not change significantly between microalbuminuric and macroalbuminuric diabetic patients (p=0.67). Serum 25-hydroxyvitamin D(3) levels correlated negatively with urinary albumin excretion (r=-0.24, p=0.016) in patients with diabetes mellitus. CONCLUSION: Findings of the present study demonstrated reduced serum 25-hydroxyvitamin D(3) levels which were significantly related with albuminuria in type 2 diabetic patients.

The association between ischaemia-modified albumin levels in umbilical vein and intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is one of the most common problems in obstetrics. Ischaemia-modified albumin (IMA), a product deriving from albumin as a result of the modification by oxidative free radicals in response to hypoxia, was previously used as a marker of ischaemia in acute coronary syndrome. We performed this study to determine whether umbilical venous IMA levels are associated with IUGR. A total of 40 pregnancies with IUGR were compared with 40 of normal fetal development. Blood samples were obtained from the umbilical vein after delivery. IMA levels in the IUGR group were higher than in the control group (78.74 ± 6.87 vs 74.43 ± 7.84 U/ml, respectively, p = 0.011). An elevated IMA level was associated with IUGR (OR: 1.079, 95% CI: 1.000-1.163, p = 0.049). We suggest that IMA, which was formerly proved to arise in ischaemic conditions, may also be a valuable marker in perinatal hypoxia and IUGR detection.

Effect of a cholesterol rich diet, recurrent infection and possible treatment modalities on the pulmonary vascular system: an experimental study.

OBJECTIVE: Infection may lead to inflammation, atherosclerosis and thrombotic vascular events. The atherosclerotic effect of hypercholesterolaemia on the vascular system is well-known. However, limited studies were done on the therapeutic and preventative agents. The aim of this study was to investigate the effects of infection and cholesterol rich diet combined with an antibiotic, anti-inflammatory agent and red wine on the pulmonary vascular system. METHODS: Fifty-nine rats were evaluated. Six groups were created: Control-Group I (n = 10); infection --Group II (n = 9), infection-cholesterol rich diet--Group III (n = 12), infection-cholesterol rich diet-cefepime--Group IV (n = II); infection-cholesterol rich diet-diclofenac potassium--Group V (n = 9); infection-cholesterol rich diet and red wine--Group VI (n = 8). Blood samples of rats were collected for cholesterol analysis every month. Sections of central pulmonary arteries were examined for thickness of the intima and medial wall by computerised image analysis. RESULTS: There was a statistically significant difference in serum cholesterol levels and in thickness of the intima between the groups (p = 0.000). The rest of the groups had more intimal thickening than Group I (p = 0.000). Group III had thicker intima than Groups IV and V (p = 0.009, p = 0.011 respectively). There was no significant difference between the groups in thickness of media (p = 0.432). CONCLUSION: Infection and cholesterol rich diet have a synergistic effect on atherosclerosis in pulmonary arteries. However antibiotics and anti-inflammatory agents could be useful in prevention.

Insulin resistance in children with Helicobacter pylori infection.

We aimed at investigating insulin resistance in children with Helicobacter pylori (H. pylori) infection. Fasting serum insulin and glucose levels were determined in 31 children with H. pylori (+) (H. pylori-infected group, 20 girls and 11 boys, median age 12 yr, range 6-17) and 29 H. pylori (-) (control group, 18 girls and 11 boys, median age 13 yr, range 5-16). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA-IR) score. Fasting serum glucose levels did not differ significantly between H. pylori (+) and (-) children. Both HOMA-IR score and serum insulin levels were significantly higher in H. pylori-infected compared to control children. The findings of the present study suggested that there is a certain relation between H. pylori infection and insulin resistance in children.

Plasma levels of nitrites, PGF1alpha, and nitrotyrosine in LPS-treated rats: functional and histochemical implications in aorta.

We investigated the effects of lipopolysaccharide (LPS) administration on plasma nitrite, nitrotyrosine and 6-keto prostaglandin F1alpha, (PGF1alpha) levels and the related resultant changes in function and histochemistry of aorta in rats. Plasma nitrite and PGF1alpha nitrotyrosine levels were analysed after 5 mg/kg intravenous LPS was administered to rats compared with those in non-treated rats. The distribution of nitrotyrosine in the aorta was studied immunohistochemically. The contractile responses of aortic rings to phenylephrine (PE) from both the LPS-treated and control rats were studied in the organ baths. There were increases in plasma nitrite, PGF1alpha, and nitrotyrosine concentrations of LPS-treated rats compared to non-treated rats. Immunoreactivity of nitrotyrosine residues were detected in the endothelial and smooth muscle cells in LPS-treated but not in control rat aorta. The contractile responses to PE of the LPS-treated rat aortic rings were significantly reduced as compared with those of control rat's. Incubation of the aortic rings from LPS-treated rats with cyclooxygenase inhibitor indomethacine or with a combination of indomethacine and nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) increased the contractile responses to the levels observed in control rats suggesting that both prostanoids and particularly nitric oxide (NO) are involved in the reduced contractile responses in LPS-treated rats. These results supported the view that LPS might cause an increment in both NO and PGI2 levels. This increase in the NO and PGI2 levels may be responsible from the reduction in responses of aorta to contractile agents in LPS-treated rats. Increased peroxynitrite formation in LPS-treated rats may lead to nitration of the tyrosil residues of the proteins in the aorta.

Erythrocyte, plasma, and serum antioxidant activities in untreated toxic multinodular goiter patients.

Erythrocyte, plasma, and serum antioxidant activities were studied in patients with newly diagnosed and untreated toxic multinodular hyperthyroid goiter and compared to healthy control subjects. Erythrocyte antioxidant enzyme activities, glutathione, malondialdehyde, and ceruloplasmin levels were significantly increased, whereas serum vitamin E, plasma vitamin C, and selenium levels were decreased in hyperthyroid patients compared to control subjects. The findings show that untreated toxic multinodular goiter causes profound alterations in components of the antioxidant system in erythrocytes indicative of increased oxidative stress. Taken together, these data suggest that hyperthyroid patients may benefit from dietary supplements of antioxidants.

The effect of experimental diabetes on cholinergic neurotransmission in rat trachea: role of nitric oxide.

We investigated the effect of nitric oxide (NO) on the responses of isolated tracheas to acetylcholine and to electrical field stimulation in streptozotocin-diabetic and controls rats. The contractile responses to acetylcholine were neither different nor affected by the NO synthase blocker, N(omega)-nitro-L-arginine methyl ester (L-NAME), in the two groups. Diabetic rat tracheas were supersensitive to field stimulation. L-NAME enhanced field stimulation-induced contractions at low frequencies in control rat tracheas, but had no effect in diabetic rat tracheas. After L-NAME treatment, there was no difference in sensitivity to field stimulation between the groups. The relaxation responses to sodium nitroprusside in acetylcholine-precontracted tracheas were not different between the groups. However, diabetic rat trachea was supersensitive to the relaxant effect of sodium nitroprusside on contractile responses to field stimulation. These results suggested that the increase in sensitivity to field stimulation in tracheas from diabetic rats might be due to impairment in the production and/or release of an endogenous NO-like factor.

Effect of the herbicide 4-CPA on human erythrocyte antioxidant enzymes in vitro.

To investigate the possible role of oxygen free radicals and oxidant stress in the toxic effects of phenoxyherbicides, we studied the in vitro effect of 4-chlorophenoxyacetic acid (4-CPA) on various human erythrocyte antioxidant enzymes, namely glucose-6-phosphate dehydrogenase, catalase, selenium-dependent glutathione peroxidase, glutathione reductase and Cu/Zn-superoxide dismutase. 4-CPA added in a dose of 1 ppm to human erythrocytes for 1 h caused a significant reduction in glucose-6-phosphate dehydrogenase (P <0.001) and catalase (P <0.001) activities, but did not significantly affect the activities of other enzymes. Such selective inactivation of specific erythrocyte antioxidant enzymes may play a role in the toxic effects of phenoxyherbicides.

The effect of nitric oxide synthase blockade on responses to morphine in rat aortic rings.

1 It has been suggested that opioids may play an indirect role in the regulation of the peripheral circulation through the control of nitric oxide (NO) release in vascular tissue. The current study was undertaken to investigate the effect of nitric oxide synthase (NOS) blockade on responses to morphine in phenylephrine (PE)- or KCl-precontracted rat aortic rings. 2 Morphine (3 x 10(-8) - 3 x 10(-5) M) administration did not cause any significant effect on basal tonus of endothelium-intact or endothelium-denuded preparations. Morphine produced concentration-dependent relaxation responses in endothelium-intact as well as in endothelium-denuded rat aortic rings precontracted by PE or KCl. Removal of endothelium did not significantly alter the relaxation responses to morphine. 3 The relaxant responses to morphine were significantly and partially inhibited by pretreatment of tissues with naloxone (NAL, 3 x 10(-5) M) for 5 min. The inhibitory effect of NAL on relaxant responses to morphine in PE- or KCl-precontracted rings did not differ significantly between endothelium-intact and endothelium-denuded preparations. 4 Incubation of endothelium-intact or endothelium-denuded rat aortic rings with NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) for 20 min did not cause a significant inhibition on relaxation responses to morphine. 5 These findings confirmed the presence of opiate receptors in rat thoracic aorta, but suggested that mechanisms other than NO release play a role in the relaxant effect of morphine on rat aortic rings.

The effects of selective phosphodiesterase III and V inhibitors on adrenergic and non-adrenergic, non-cholinergic relaxation responses of guinea-pig pulmonary arteries.

1. The aim of the present study was to investigate the role of several possible neurotransmitters in mediating non-adrenergic, non-cholinergic (NANC) relaxation, and the effects of phosphodiesterase (PDE) III and V inhibitors on adrenergic and NANC relaxation in branch pulmonary artery (PA) of guinea-pig. 2. Under the NANC conditions, electrical field stimulation (EFS, 60 V, 0.2 ms, 20 Hz) induced a tetrodotoxin-sensitive relaxation of the histamine-precontracted PA rings. The nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10(-4) m) and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10(-5) m) partially inhibited the EFS-induced relaxation. The inhibitory effect of l-NAME was reversed completely by l-arginine (10(-3) m), but not d-arginine (10(-3) m). 3. This NANC relaxation was attenuated by 8-phenyltheophylline (10(-5) m), a P1-purinoceptor antagonist. 4. The NANC response was potentiated by 10-6 m zaprinast, a type V PDE inhibitor, but was unaffected by 3 x 10-6 m milrinone, a type III PDE inhibitor. 5. Sodium nitroprusside (SNP) caused a concentration-dependent vasodilator effect which was potentiated by zaprinast, but unaffected by milrinone. Moreover, the effect of combination of zaprinast with milrinone was not significantly different from that observed with zaprinast alone. 6. Isoprenaline produced a concentration-dependent vasodilatation in branch PA of guinea-pig which was potentiated by both zaprinast and milrinone, the efficacy of milrinone being greater than zaprinast. 7. These results suggest that both nitrergic and purinergic pathways are involved in mediating the NANC relaxation in branch PA of guinea-pig. The combination of PDE III or V inhibitors with vasorelaxant drugs may be a hopeful approach for the treatment of pulmonary hypertension.

Ischemia modified albumin levels cannot predict stress induced ischemia shown by myocardial perfusion scintigraphy.

PURPOSE: Ischemia modified albumin (IMA) is a new marker of ischemia which is used in especially emergency room. Aim of this study is showing the association of IMA with stress induced ischemia on Tc-99m 2-methoxyisobutyl-nitrate (MIBI) myocardial perfusion scintigraphy (MPS). METHODS: 56 patients (23 F, 33 M; 56.04 ± 8.45 years old) were included in our study. Stress-rest two days protocol Tc-99m MIBI MPS single photon emission tomography (SPECT) was performed to all patients. IMA levels from the blood samples which were taken before and after the treadmill test were measured. Thirty patients additionally underwent coronary angiography. RESULTS: The difference of IMA levels of ischemia between positive and negative groups was not statistically significant. Also, there was not statistically significant difference between IMA levels of patients who have narrowing in the coronary arteries and not. CONCLUSION: Although IMA is an important marker of ischemia, probably because of other ischemic process during stress; it cannot reflect stress induced ischemic changes on MPS.

Impairment of endothelium-dependent vasorelaxation in cadmium-hypertensive rats.

Abnormalities in the production and/or release of relaxing factors from the endothelium have been implicated in the development of hypertension in several animal models. Endothelium-dependent relaxation has been reported to be impaired in thoracic aorta in experimentally induced and genetically hypertensive rats. Present study has extented these observations to thoracic aorta of cadmium-hypertensive rats. The possible role of alterations in oxidant status was also studied. Hypertension was induced by the intraperitoneal administration of 1 mg/kg/day cadmium for 15 days. Mechanical responses produced by acetylcholine (ACh, 10(-9)-10(-4) M) and sodium nitroprusside (SNP, 10(-10)-10(-5) M) were studied on phenylephrine-precontracted thoracic aorta rings from control and cadmium-hypertensive rats. Serum nitric oxide (NO) and aortic malondialdehyde (MDA) levels were measured. ACh-induced relaxation was attenuated in aorta from cadmium-hypertensive rats, whereas relaxation responses to SNP did not differ significantly between the groups. Exposure of aortic rings to N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) resulted in a significantly greater inhibition of relaxation response to ACh in aortic rings of cadmium-hypertensive rats as compared with control rats. Incubation with L-arginine (L-Arg, 10(-3) M) caused a similar reversal of the inhibition of ACh-induced relaxation by L-NAME in both groups. Serum NO levels were decreased and aortic MDA levels were increased in cadmium-treated rats as compared with control rats. However, the differences between the groups did not reach a statistical significance. These findings suggested that the reduction in endothelium-dependent relaxation may play a role in cadmium-induced hypertension as it was in many other hypertension models.

Plasma homocysteine levels in patients with beta-thalassaemia major.

OBJECTIVE: We investigated the level of homocysteine (HCY) and its relation with vitamin B12, folate and oxidative stress in patients with beta-thalassaemia major. MATERIAL AND METHODS: Plasma HCY, methionine, advanced oxidation protein products (AOPP) and serum vitamin B12, folate, ferritin and total antioxidant capacity (TAC) were determined in 32 thalassaemic patients and 27 control subjects. RESULTS: HCY (6.44+/-0.44 versus 8.71+/-0.57 micromol/L), methionine (12.57+/-1.8 versus 22.2+/-3.8 micromol/L), folate (9.14+/-0.48 versus 15.38+/-0.71 nmol/L) and TAC (0.34+/-0.03 versus 0.56+/-0.03 mmol/L) significantly decreased in thalassaemic patients, whereas AOPP (20.26+/-1.8 versus 11.30+/-0.2 micromol/L) and ferritin (3481.0+/-512 versus 46.9+/-4.6 ng/mL) significantly increased. Vitamin B12 levels were similar in both groups (259.1+/-16.6 versus 228.9+/-7.4 pmol/L). CONCLUSIONS: These findings suggest that increased and uncompensated oxidative stress may lead to an increment in HCY catabolism in thalassaemic patients.

Single-dose depot leuprolide is as efficient as daily short-acting leuprolide in ICSI cycles.

BACKGROUND: In this prospective randomized study, we aimed to compare the efficacy of a single depot (1.88 mg) reduced dose with a daily low dose (0.5 mg/day) of leuprolide for pituitary suppression as part of controlled ovarian hyperstimulation (COH) in an ICSI program. METHODS: The study population consisted of 103 patients randomized into two groups. Group 1 (n = 52) consisted of patients who had daily low-dose leuprolide injections. Group 2 (n = 51) consisted of patients who had the 1.88 mg single-dose leuprolide injection. RESULTS: The age of the patients, the number of metaphase II oocytes, the number and quality of embryos transferred were similar between the two groups. Although the length of gonadotrophin stimulation was significantly longer in group 2 (P < 0.01), the amount of gonadotrophins used was similar (P = 0.34). Leuprolide levels were significantly lower in group 2 within the first 8 h after injection (P < 0.05), but no difference was observed thereafter. Although LH levels on the day of hCG (P = 0.06) administration and estradiol levels on day 3 (P < 0.01) were lower in group 2, LH levels and progesterone levels 1 week after embryo transfer did not show any statistically significant difference. Clinical pregnancy rates per embryo transfer, implantation rates and first trimester abortion rates were also similar for both groups. CONCLUSIONS: A single reduced depot dose (1.88 mg) of leuprolide was found to be as effective as classical long multi-dose protocol for pituitary desensitization in COH for ICSI cycles.

Experimental hyperhomocysteinemia disturbs bone metabolism in rats.

OBJECTIVE: To investigate whether experimental hyperhomocysteinemia (HHCY) can induce adverse changes in bone metabolism. METHODS: Blood and urine samples were collected from rats fed with a methionine-enriched diet (HHCY, n = 18) or an isocaloric control diet (control, n = 10) for 12 weeks. Biochemical bone turnover markers (osteocalcin, hydroxyproline, N-terminal collagen I telopeptides and homocysteine (HCY), folate and vitamin B12) were measured. Whole body bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. RESULTS: HCY was significantly higher in HHCY than in control rats (16.2 versus 3.2 micromol/L; p = 0.0006). Bone resorption parameters hydroxyproline (1.60 +/- 0.6 versus 0.85 +/- 0.4; p<0.05) and N-terminal collagen I telopeptides (150.8 +/- 78 versus 48.1 +/- 26 nmol/L BCE; p<0.05) increased, whereas bone formation marker osteocalcin (9.01 +/- 3.8 versus 15.07 +/- 4.2 ng/mL; p<0.05) decreased in HHCY compared to control rats. The relation N-terminal collagen I telopeptides/osteocalcin significantly increased in HHCY compared to control rats (13.14 +/- 3.1 versus 4.14 +/- 1.9). BMD measurement did not reveal any differences between groups. CONCLUSION: These findings demonstrate a significant modification of bone turnover in HHCY rats. The relation between bone resorption and formation indicates a shift toward bone resorption, which might be a plausible explanation for the relation between HHCY and fracture risk.

Effect of a cholesterol rich diet, recurrent infection and possible treatment modalities on the pulmonary vascular system: an experimental study / Efecto de la dieta rica en colesterol, la infección recurrente, y las posibles modalidades de tratamiento sobre el sistema vascular pulmonar: un estudio experimental

OBJECTIVE: Infection may lead to inflammation, atherosclerosis and thrombotic vascular events. The atherosclerotic effect of hypercholesterolaemia on the vascular system is well-known. However, limited studies were done on the therapeutic and preventative agents. The aim of this study was to investigate the effects of infection and cholesterol rich diet combined with an antibiotic, anti-inflammatory agent and red wine on the pulmonary vascular system. METHODS: Fifty-nine rats were evaluated. Six groups were created: Control-Group I (n = 10); infection - Group II (n = 9), infection-cholesterol rich diet - Group III (n = 12), infection-cholesterol rich dietcefepime - Group IV (n = 11); infection-cholesterol rich diet-diclofenac potassium - Group V (n = 9); infection-cholesterol rich diet and red wine - Group VI (n = 8). Blood samples of rats were collected for cholesterol analysis every month. Sections of central pulmonary arteries were examined for thickness of the intima and medial wall by computerised image analysis. RESULTS: There was a statistically significant difference in serum cholesterol levels and in thickness of the intima between the groups (p = 0.000). The rest of the groups had more intimal thickening than Group I (p = 0.000). Group III had thicker intima than Groups IV and V (p = 0.009, p = 0.011 respectively). There was no significant difference between the groups in thickness of media (p = 0.432). CONCLUSION: Infection and cholesterol rich diet have a synergistic effect on atherosclerosis in pulmonary arteries. However, antibiotics and anti-inflammatory agents could be useful in prevention.

OBJETIVO: La infección puede conducir a inflamación, ateroesclerosis y eventos vasculares trombóticos. El efecto aterosclerótico de la hipercolesterolemia en el sistema vascular es bien conocido. Sin embargo, se hicieron estudios limitados sobre los agentes preventivos y terapéuticos. El objetivo de este estudio fue investigar los efectos de la infección y la dieta rica en colesterol, combinados con agentes antibióticos, anti-inflamatorios, y vino tinto, sobre el sistema vascular pulmonar. MÉTODOS: Cincuenta y nueve ratas fueron evaluadas. Se hicieron seis grupos: grupo-control I (n = 10), grupo-infección II (n = 9), grupo infección-dieta rica en colesterol III (n = 12), grupo-infección-dieta rica en colesterol-cefepima IV (n = 11), grupo-infección-dieta rica en colesterol-diclofenaco potásico V (n = 9), grupo-infección-dieta rica en -vino tinto VI (n = 8). Se tomaron muestras de sangre de ratas para analizar el colesterol cada mes. Se examinaron secciones de las arterias pulmonares centrales para determinar el grosor de la pared íntima y media mediante análisis computarizado de imágenes. RESULTADOS: Hubo una diferencia estadísticamente significativa en los niveles de colesterol en suero y el grosor de la íntima entre los grupos (p = 0.000). El resto de los grupos tenía más engrosamiento de la íntima que el grupo I (p = 0.000). El grupo III tenía una íntima más gruesa que los grupos IV y V (p = 0,009, p = 0.011 respectivamente). No hubo ninguna diferencia significativa entre los grupos en cuanto al espesor de la media (p = 0.432). CONCLUSIÓN: La infección y la dieta rica en colesterol tienen un efecto sinérgico sobre la aterosclerosis en las arterias pulmonares. Sin embargo, los antibióticos y los agentes antiinflamatorios podrían ser útiles para la prevención.

Effects of propylthiouracil treatment on antioxidant activities in blood of toxic multinodular goiter patients.

Erythrocyte, serum and plasma antioxidant activities and the effects of propylthiouracil (PTU) treatment on these activities were studied in patients with toxic multinodular goiter. The activities of the erythrocyte antioxidant enzymes (glucose-6-phosphate dehydrogenase, catalase, Cu/Zn-superoxide dismutase, selenium (Se)-dependent glutathione peroxidase and glutathione reductase) and the levels of erythrocyte Se, serum ceruloplasmin and plasma malondialdehyde were significantly higher while serum vitamin E, plasma vitamin C and plasma Se were lower in hyperthyroid patients. PTU treatment, not for 1 but for 3 months caused a partial reversal of antioxidant activities to euthyroid levels. It is suggested that alterations in blood antioxidant activities following PTU treatment might be due to the antioxidant and/or antithyroid effect of this drug.

Responsiveness of aortic rings of cadmium-hypertensive rats to endothelin-1.

Cadmium administered intraperitoneally at a dose of 1 mg/kg/day for 15 days caused a significant increase in mean arterial blood pressure. Endothelin-1 and noradrenaline produced concentration-dependent contractions of aortic rings that attained a lower maximal contraction in cadmium-injected rats as compared with control rats (p < 0.05). On the other hand, responses of aortic rings to different concentrations of potassium chloride did not show a significant difference between the groups. The decreased responsiveness of the aortae of cadmium-hypertensive rats to endothelin-1 and noradrenaline could either be due to an interaction of cadmium with receptors or intracellular signal transduction pathways of these agents, or it may simply reflect the adaptive changes in vascular tissues following hypertension development.