Endogenous nitric oxide and exogenous nitric oxide supplementation in hepatic ischemia-reperfusion injury in the rat

BACKGROUND: Although nitric oxide (NO) is thought to be beneficial in hepatic ischemia-reperfusion (I/R), the mechanisms for this effect are not well established. METHODS: To investigate the effects of endogenous NO and exogenous NO supplementation on hepatic I/R injury and their pathogenic mechanisms, serum ALT and hyaluronic acid (endothelial cell damage), and hepatic malondialdehyde and H2O2 (oxidative stress), myeloperoxidase activity (leukocyte accumulation), and endothelin (vasoconstrictor peptide opposite to NO) were determined at different reperfusion periods in untreated rats and rats receiving L-NAME, L-NAME+L-arginine, and spermine NONOate (exogenous NO donor). RESULTS: After reperfusion every parameter increased in untreated animals. Endogenous NO synthesis inhibition by L-NAME increased hepatocyte and endothelial damage as compared to untreated rats, which was reverted and even improved by the addition of L-arginine. Spermine NONOate also improved this damage. However, different mechanisms account for the beneficial effect of endogenous and exogenous NO. Oxidative stress decreased by both L-NAME and L-NAME+L-arginine, but remained unmodified by spermine NONOate. Myeloperoxidase increased by L-NAME and this effect was reverted by the addition of L-arginine, whereas no change was observed with spermine NONOate. Endothelin levels were not modified by L-NAME and L-NAME+L-arginine, but decreased with spermine NONOate. CONCLUSIONS: These results suggest that, although both endogenous and exogenous NO exert a protective role in experimental hepatic I/R injury, the mechanisms of the beneficial effect of the two sources of NO are different.     

Doppler ultrasonographic and scintigraphic assessment of an auxiliary heterotopic liver transplantation with portal vein arterialization in pigs

OBJECTIVE: Our aim was to evaluate liver graft integrity and function using scintigraphy and ultrasonography in a porcine model of auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA). MATERIALS AND METHODS: Using Doppler ultrasonography we evaluated eight AHLT-PVA by parenchymal echogenicity, portal and arterial anatomy, and portal and biliary system flow. Two types of scintigraphy were performed: microaggregated human albumin colloid scintigraphy and diisopropyl iminodiacetic acid (DISIDA) scintigraphy, both labeled with 99mTc. RESULTS: The animals were distributed into two groups. The first group consisted of three animals with clinical suspicion of graft dysfunction, in which the ultrasonographic study revealed areas of parenchymal destructuring. In the scintigraphic study, heterogenous uptake was observed; there was no uptake in one animal. Necropsy of these three animals revealed areas of graft necrosis. The second group consisted of five animals with good clinical evolutions, in which the ultrasonographic study showed portal dilation, portal flow with arterial spiculations, and homogenous echogenicity of the hepatic parenchyma. The scintigraphic study revealed homogenous uptake by the graft and an elimination speed of the hepatobiliary agent similar to that of the native liver. CONCLUSIONS: An heterogenous echostructure of the graft provided a sign of poor prognosis indicating necrosis in the same way as heterogenous uptake or nonuptake of radioisotope upon scintigraphy. Scintigraphy is a good method to evaluate biliary function and bile elimination. In an AHLT-PVA, the main ultrasound findings derived from arterialization were dilation of the portal system and portal flow with arterial spiculations.     

Sublinear summation of afferent inputs to the nucleus accumbens in the awake rat

The mechanisms by which the nucleus accumbens integrates afferent input from limbic and cortical structures have been influential in the development of models of psychiatric disorders such as schizophrenia. Previous studies of the response of nucleus accumbens (Nacb) cells to the stimulation of afferent inputs from hippocampus (HC) and prefrontal cortex (PFC) have demonstrated that PFC throughput can be modulated by preceding HC input. Examination of the post-synaptic potential size has suggested, however, that summation of these inputs is sublinear. All studies to date examining Nacb integration of inputs via stimulation of afferents have been performed in the anaesthetized rat. The present experiments compare the response of Nacb cells to different combinations of PFC and HC stimulation in awake and isoflurane-anaesthetized rats that were chronically implanted with both stimulating and recording electrodes. The results of these experiments suggest that summation of afferent input in the Nacb of the awake rat is predominantly sublinear, with only a minority of neurons demonstrating modulation of PFC inputs by the HC in the awake or the anaesthetized animal. The response profile of many cells changed during anaesthesia when compared to the awake condition, and on average showed suppression to PFC input 50 and 150 ms following HC stimulation while under deep isoflurane anaesthesia. These results suggest that sublinear integration of afferent input from the PFC and HC is the dominant mode of integration of Nacb cells in the awake animal, which has implications for corticostriatal models of psychiatric dysfunction.     

Dual-photon bone densitometry in dialyzed patients

In non-invasive diagnosis of renal osteodystrophy the levels of bone minerals and the extent of bone turnover are evaluated. The contents of bone minerals are assessed quantitatively by different modalities of bone densitometry, among which the most accurate one is double-energy bone densitometry. So far no standard examination method was defined nor the most suitable portion of the skeleton for densitometric examination. In order to find such an area and also to assess the prevalence of bone demineralization, its severity and regional differences the authors made a cross-sectional study of bone density in dialyzed patients. The group comprised 45 patients, 24 men and 21 women subjected to regular dialyzation treatment for 20-24 months. In a lambda whole body bone densitometry was performed with evaluation of regional densities of the trunk, upper and lower extremities. At the same time the state of bone turnover was assessed arbitrarily using values of serum concentrations of intact parathormone; parathormone concentrations below 50 pg/ml were considered low, above 200 pg/ml high and concentrations within the mentioned range as the normal bone turnover. In the group of patients 62% had a high, 22% a normal and 16% a low bone turnover. The study provided evidence of a significant reduction of bone density (Z score <-1) in 58% of patients. In 92% of patients demineralization affected most and first the extremities. In 69% it affected the lower extremities and in 23% the upper ones. 8% of the patients had the most severe affections in the area of the trunk. This order of affliction was not influenced by bone turnover, sex and in women by age. The diaphysis of long bones seems to be a representative examination area of the skeleton for densitometric measurements in patients with regular dialyzation treatment.     

Plasminogen activator inhibitor-I (PAI-I) polymorphisms in patients with obstructive sleep apnoea

Cardiovascular diseases are frequent among patients with the obstructive sleep apnoea syndrome (OSAS), The aetiopathogenesis of this association is unclear. Type 1 plasminogen activator inhibitor (PAI-1) is one of the primary regulators of the fibrinolytic system. A reported association between PAI-1 activity and an insertion/deletion polymorphism (4G/5G) in the promoter region of the PAI-1 gene suggests a critical role for this genomic region in the pathogenesis of several cardiovascular diseases. In this study, we determined the prevalence of this polymorphism in patients with OSAS and in healthy control subjects. The 4G/5G polymorphism in the promoter region of the PAI-1 gene was determined in 78 male patients with severe OSAS (56 +/- 2 apnoeas per hour) and in 70 healthy male, non-smoker volunteers of similar age, without personal or familial history of cardiovascular disease. The frequency ofthe 4G/4G, 4G/5G and 5G/5G genotypes in patients with OSAS (18%, 62%, 19%, respectively) was not significantly different from that seen in healthy subjects (16%, 60%, 24% P=NS). These results show that the distribution of the 4G/5G polymorphism in the promoter region ofthe PAI-1 gene in patients with OSAS is similar to that observed in healthy subjects. This observation suggests that the PAI-1 polymorphism has no relationship with the increased risk of cardiovascular diseases seen in patients with OSAS.     

Thyroid disease in primary Sjögren syndrome. Study in a series of 160 patients

We studied 160 consecutive patients (147 female and 13 male) with primary Sj?gren syndrome (SS) to determine the prevalence and clinical significance of thyroid disease in a large series of patients with primary SS from our unit and to compare the prevalence and significance with those in 75 individuals without SS from a primary care center. Serum levels of thyroid hormones (free thyroxine, triiodothyronine, and thyroid-stimulating hormone) and autoantibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) were measured in all SS patients and in 75 control patients. Fifty-eight (36%) of the 160 patients with primary SS had evidence of thyroid disease. Autoimmune thyroid disease (ATD) was diagnosed in 32 (20%) patients and nonautoimmune thyroid disease (NATD) in 26 (16%). No significant differences were found when these prevalences were compared with those in control patients. On the other hand, comparing those patients with altered hormonal profiles, patients with NATD showed mainly hyperthyroidism (10/17, 59% versus 2/20, 10% in patients with ATD, p = 0.001). Finally, when clinical and immunologic manifestations of SS were analyzed in patients with and without thyroid disease, respectively, we found that patients with thyroid disease had a higher prevalence of female gender (98% versus 88%, p = 0.03), antiparietal cell autoantibodies (33% versus 12%, p = 0.002), TgAb (30% versus 5%, p < 0.001), and TPOAb (40% versus 5%, p < 0.001). In conclusion, thyroid disease occurred in more than one-third of patients with primary SS; the main cause was ATD, which was present in 20% of the patients studied. We note that no significant differences were observed when the prevalence of thyroid disease (either ATD or NATD) was compared with that in a control group of similar age and gender. Our results indicate that middle-aged women (with or without SS) should be screened periodically for thyroid function.     

Severe pulmonary hypertension and Takayasu arteritis

Takayasu arteritis is an inflammatory disease that affects large vessels, especially the aorta and its branches. The clinical features of the disease depend on which arteries are affected. Although pulmonary artery involvement is common, only rarely is this the main clinical manifestation. We describe the case of a young woman with dyspnea who had severe pulmonary hypertension secondary to Takayasu arteritis of the pulmonary artery. She was administered corticosteroid (methylprednisolone) and immunosuppressant (azathioprine) therapy and a stent was implanted in the left pulmonary artery. Both hemodynamic and clinical signs improved.     

Body composition and newborn birthweight in pregnancies of adolescent and mature women

Teenage pregnancy has been associated with adverse effects for the mother and the newborn (NB). In order to compare body composition (BC) between adolescents (Ad) and mature women (MW) during pregnancy and to determine the difference in birthweight and perinatal morbidity, pregnant Ad (n = 40) and MW (n = 227) were studied. BC changes between the second and third trimesters were determined by multifrequency bioelectrical impedance analysis, and birthweight and NB morbidity were evaluated. During the second and third trimesters of the pregnancy, fat mass was lower in the Ad group [16 kg (13–19)] than in the MW group [22 kg (17–27)] (P < 0.01; median and quartiles 1–3). Fat‐free mass increased by 3.09 kg (2.29–4.20) and 2.20 kg (1.0–3.59) (P ≤ 0.01), and total body water increased by 2.77 L (0.84–4.49) vs. 2.04 L (0.55–3.89) (P = 0.36), in the Ad and MW groups, respectively (median and quartiles 1–3). Birthweight was not significantly different between NBs of Ad (3223 ± 399 g) and NBs of MW (3312 ± 427 g, P = 0.22). The youngest Ad (<18 year old, n = 8) had NB with lower birthweight than MW (3031 ± 503 g, P = 0.06). NBs of Ad mothers showed a non‐significant trend towards a higher rate of morbidity relative to the NBs of MW. In conclusion, the BC of Ad differs from that of MW during pregnancy. In addition, the NB infants of Ad mothers tended to have a lower birthweight than those from MW, a result that suggests that the Ad should be in strict prenatal control.