[Management of psychological trauma in primary care]. / Trauma psicológico en la atención primaria: orientaciones de manejo.

Exposure to traumatic events is frequent in the general population and psychiatric sequelae such as post-traumatic stress disorders are common. The symptoms of psychiatric sequelae after trauma are vague, with multiple psychological and physical symptoms, which can confuse the health care professional. This paper seeks to facilitate the work in primary care, providing practical information about the diagnosis, initial management and referral of patients who have suffered traumatic experiences. Some early interventions and treatments are suggested.

Trauma psicológico en la atención primaria: orientaciones de manejo / Management of psychological trauma in primary care

Exposure to traumatic events is frequent in the general population and psychiatric sequelae such as post-traumatic stress disorders are common. The symptoms of psychiatric sequelae after trauma are vague, with multiple psychological and physical symptoms, which can confuse the health care professional. This paper seeks to facilitate the work in primary care, providing practical information about the diagnosis, initial management and referral of patients who have suffered traumatic experiences. Some early interventions and treatments are suggested.

Effect of losartan on early liver fibrosis development in a rat model of nonalcoholic steatohepatitis.

BACKGROUND AND AIM: Nonalcoholic steatohepatitis (NASH) is a metabolic disorder of the liver that may evolve into fibrosis or cirrhosis. Recent studies have shown reduction of experimental liver fibrosis with the use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor antagonists. The aim of this study was to determine whether losartan can influence the early phase of fibrogenesis in an animal model of NASH. METHODS: To induce NASH, a choline-deficient diet (CDD) was given to Sprague-Dawley rats for 12 weeks. These animals were then compared with a control group receiving choline-supplemented diet (CSD) and a group fed a CDD plus losartan (10 mg/kg/day). Biochemical (serum levels of alanine aminotransferase and aspartate aminotransferase) and histological evaluation of fatty liver was performed by conventional techniques. Hydroxyproline content in liver tissue was assayed by spectrophotometry. In addition, mRNA levels of procollagen I and transforming growth factor (TGF)-beta were assessed by semiquantitative RT-PCR and stellate cell activation by alpha-actin immunofluorescence stain. RESULTS: After 12 weeks CDD induced a marked elevation of serum aminotranferases, a severe fatty liver infiltration with mild histological inflammation and fibrosis. These findings correlated with a significant increase in mRNA levels of both procollagen I and TGF-beta and significant increased liver hydroxyproline content. No differences were seen between rats receiving CDD alone and rats receiving CDD plus losartan with regard to the biochemical, morphological or molecular alterations induced by the CDD. CONCLUSION: Losartan does not seem to influence liver injury and fibrogenic events in the CDD model of NASH.

Pentoxifylline does not prevent neither liver damage nor early profibrogenic events in a rat model of non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a metabolic disorder of the liver, which may evolve to fibrosis or cirrhosis. Pentoxifylline (PTX) has been postulated to act as an antifibrogenic agent able to inhibit hepatic stellate cell proliferation and collagen synthesis in vitro. Short-term studies suggest beneficial effects of PTX in experimental models of NASH. AIM: To study whether PTX can influence liver fibrogenesis in an animal model of NASH. METHODS: To induce NASH, a choline-deficient diet (CDD) was given to Sprague- Dawley rats for 8 weeks. Rats were allocated to two experimental groups one receiving PTX (9 mg/kg/day) in drinking water. Control rats received a choline-supplemented diet. Biochemical and histological evaluation of fatty liver was performed by conventional techniques. In addition, mRNA levels of Pro-collagen I and transforming growth factor beta-1 were assessed by semi-quantitative RT-PCR and stellate cell activation by alpha-actin immunofluorescence stain. RESULTS: After 8 weeks CDD induced a marked elevation of serum aminotransferases, a marked decrease in both hepatic and biliary glutathione and a severe fatty liver infiltration with mild histological inflammation and fibrosis. A significant increase in mRNA levels of both Pro-collagen I and TGFbeta-1 was seen after CDD feeding. No differences were seen between rats receiving PTX and rats on CDD diet alone with regard to the biochemical, morphological or molecular alterations induced by the CDD. CONCLUSION: PTX does influence neither liver injury nor early profibrogenic events in the CDD model of NASH.

Bile secretory function after warm hepatic ischemia-reperfusion injury in the rat.

Hepatic ischemia-reperfusion (I-R) injury frequently is associated with cholestasis. However, the underlying mechanisms are not fully understood. The aim of the study is to assess bile secretory function in vivo in rats subjected to warm lobar hepatic ischemia at different times during reperfusion. A model of lobar 70% warm hepatic ischemia for 30 minutes was used with studies conducted at 1 and 6 hours and 1, 3, and 7 days after reperfusion. Bile secretory function was assessed after selective cannulation of bile ducts of ischemic (ILs) and nonischemic lobes (NILs). Serum activity of hepatic alanine and aspartate aminotransferase was slightly increased in rats subjected to I-R, whereas serum bile salt levels increased early during reperfusion, returning to control values after 7 days. ILs showed mild reversible leukocyte infiltration and no significant necrosis. Bile flow and bile salt excretion were significantly decreased in ILs during the first 24-hour reperfusion period compared with sham-operated rats and NILs. A marked reduction in glutathione (GSH) excretion occurred at 1 and 6 hours and 1 and 3 days, which returned to control values after 7 days. Total GSH and both reduced and oxidized GSH levels in liver homogenate and arterial blood GSH levels were unchanged at all times. Protein mass of multidrug resistance protein 2 and its function, assessed by the hepatic maximum secretory rate of ceftriaxone, did not show significant changes in ILs or NILs compared with sham-operated rats. Liver tissue gamma-glutamyl transpeptidase (GGT) and gamma-glutamylcysteine synthetase activities remained unchanged, whereas biliary GGT and cysteine secretory rates were significantly increased in ILs and NILs. Administration of acivicin, a GGT inhibitor, resulted in decreased secretion of this enzyme into bile and a parallel marked increase in biliary GSH secretion compared with untreated ischemic rats. In conclusion, warm hepatic I-R induces reversible cholestatic changes in ILs. GSH secretory rates from both ILs and NILs were markedly decreased during reperfusion. The reversibility of this effect after GGT inhibition, as well as increased release of active GGT into bile and cysteine biliary secretory rates, suggest increased GSH degradation in bile. These findings might be relevant for the I-R-induced clinical cholestasis, as well as cholangiocyte injury, seen after hepatic ischemia.

Down-regulation of the Na+/taurocholate cotransporting polypeptide during pregnancy in the rat.

BACKGROUND: Experimental studies have shown decreased bile acid (BA) uptake and reduced excretion of cholephilic compounds in pregnant rodents. AIM: To assess the expression and function of the main BA importer, the Na(+)/taurocholate cotransporting polypeptide (Ntcp) in pregnant rats. METHODS: BA uptake and Ntcp expression were studied in control and timed-pregnant rats in late gestation. Ntcp protein, messenger RNA (mRNA) expression, and Ntcp tissue localization were determined by Northern blotting, Western analysis, and tissue immunofluorescence. The activity of three transactivators of the Ntcp promoter: hepatocyte nuclear factor 1-alpha (HNF1-alpha), nuclear receptor heterodimer retinoid X receptor:retinoid acid receptor (RXR:RAR) and signal transducer and activator of transcription 5 (Stat5) was assessed using gel electrophoretic mobility shift assays. RESULTS: A significantly reduced BA uptake and decreased Ntcp mRNA levels (-40%) and protein mass (-60%) was observed in pregnant rats. Nuclear extracts from pregnant rats showed a marked decrease of HNF1-alpha and RXR:RAR binding activities by -80 and -40% of basal activity, respectively. In contrast, binding activity of Stat-5 was increased by 50% in nuclear extracts from pregnant rats. CONCLUSIONS: Pregnancy is associated with reduced Ntcp expression and function in the rat. Our findings suggest that Ntcp down-regulation during pregnancy occurs primarily at the transcriptional level.

Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators.

Hepatocyte gap junction proteins, connexins (Cxs) 26 and 32, are downregulated during obstructive cholestasis (OC) and lipopolysaccharide hepatocellular cholestasis (LPS-HC). We investigated rat hepatic Cxs during ethynylestradiol hepatocellular cholestasis (EE-HC) and choledochocaval fistula (CCF) and compared them with OC and LPS-HC. Levels (immunoblotting) and cellular distribution (immunofluorescence) of Cx26, -32, and -43, as well as macrophage infiltration, were studied in livers of rats under each condition. Cx26 and -32 were reduced in LPS-HC, OC, and CCF. However, in EE-HC, Cx26 did not change and Cx32 was increased. Prominent inflammation occurred in LPS-HC, OC, and CCF, which was associated with increased levels of Cx43 in LPS-HC and OC but not CCF. No inflammation nor changes in Cx43 levels occurred during EE-HC. In cultured hepatocytes, dye coupling was reduced by tumor necrosis factor-alpha and interleukins-1beta and -6, whereas reduction induced by LPS required coculture with Kupffer cells. Thus hepatocyte gap junctions are downregulated in forms of cholestasis associated with inflammation, and reduced intercellular communication might be induced in part by proinflammatory mediators.

From blood to bile: recent advances in hepatobiliary transport.

Transport of endogenous and exogenous substances from blood to bile is an essential function of the liver. In the last decade a still growing number of specific transport proteins present at the sinusoidal and canalicular membrane domains of hepatocytes and cholangiocytes have been cloned and functionally characterized. Studies assessing the molecular expression and function of these hepatobiliary transport proteins under different experimental conditions has helped to define the adaptive responses of hepatocytes to certain physiological states and to cholestatic liver injury and to a better understanding of the physiology of bile formation and of the pathophysiology of certain cholestatic diseases. Particularly relevant is the elucidation of the molecular bases of several forms of inherited cholestatic liver disease, which may help to the development of better diagnostic tools or to the design of new therapeutic strategies. In the present review we summarize recent experimental and clinical data involving hepatobiliary transport mechanisms.