Remote ischemic preconditioning as treatment for non-ischemic gastrointestinal disorders: beyond ischemia-reperfusion injury

Common gastrointestinal diseases such as radiation enteritis (RE), acute pancreatitis, inflammatory bowel diseases (IBD) and drug-induced hepatotoxicity share pathophysiological mechanisms at the molecular level, mostly involving the activation of many pathways of the immune response, ultimately leading to tissue injury. Increased oxidative stress, inflammatory cytokine release, inflammatory cell infiltration and activation and the up-regulation of inflammatory transcription factors participate in the pathophysiology of these complex entities. Treatment varies in each specific disease, but at least in the cases of RE and IBD immunosuppressors are effective. However, full therapeutic responses are not always achieved. The pathophysiology of ischemiareperfusion (IR) injury shares many of these mechanisms. Brief and repetitive periods of ischemia in an organ or limb have been shown to protect against subsequent major IR injury in distant organs, a phenomenon called remote ischemic preconditioning (RIP). This procedure has been shown to protect the gut, pancreas and liver by modulating many of the same inflammatory mechanisms. Since RIP is safe and tolerable, and has shown to be effective in some recent clinical trials, I suggest that RIP could be used as a physiologically relevant adjunct treatment for non-ischemic gastrointestinal inflammatory conditions

Social networks in medical practice

The number of social network users is rising meteorically, a trend that also includes health-care workers. Even though social networking can serve educational functions and is an effective means of communicating medical resources, it is associated with a variety of important challenges. Misuse of social networks by health-care workers can have dire consequences, ranging from seemingly simple issues such as affecting the doctor’s reputation to serious legal matters. Maintaining professionalism and preserving the concepts of confidentiality and privacy is essential. In this review we will analyze some of the dilemmas that have been brought about by the use of social networks in the healthcare environment, as well as existing guidelines on the matter

Increased cerebrospinal fluid levels of cytokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in patients with amyotrophic lateral sclerosis

Introduction: Neuroinflammation has recently been described in amyotrophic lateral sclerosis (ALS). However, the precise role of such proinflammatory cytokines as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1� (MIP-1�) in ALS has not yet been determined. In this study, we determined cerebrospinal fluid (CSF) MCP-1 and MIP-1� levels and assessed their association with the duration and severity of ALS. Methods: Concentrations of MCP-1 and MIP-1� were determined in the CSF of 77 patients diagnosed with ALS and 13 controls. Cytokine levels were analysed in relation to ALS duration ( 12 months) and severity ( 30 points on the ALS Functional Rating Scale administered at hospital admission). Results: Higher CSF MIP-1� (10.68 pg/mL vs 4.69 pg/mL, P < .0001) and MCP-1 (234.89 pg/mL vs 160.95 pg/mL, P = .011) levels were found in the 77 patients with ALS compared to controls. There were no differences in levels of either cytokine in relation to disease duration or severity. However, we did observe a significant positive correlation between MIP-1� and MCP-1 in patients with ALS. Conclusions: The increase in MIP-1� and MCP-1 levels suggests that these cytokines may havea synergistic effect on ALS pathogenesis. However, in our cohort, no association was found witheither the duration or the clinical severity of the disease

Mean platelet volume in the differential diagnosis of tuberculous and bacterial meningitis

Abstract Introduction: Mean platelet volume (MPV) has been shown to reflect the inflammatory burden in different inflammatory and autoimmune diseases. Our objective was to analyze the MPV in patients with tuberculous (TBM) and bacterial meningitis (BM). Methodology: The demographic and clinical data of 73 consecutive patients that presented with either BM (n = 35) or TBM (n = 38) were retrospectively analyzed, as well as that of 28 age- and sex-matched controls. Results: MPV was 8.78 ± 1.58 fL in patients with BM and 6.42 ± 1.39 fL in the TBM group (p < 0.05). In the control group, MPV was 7.4 ± 0.66 fL, significantly higher and lower when compared with TBM and BM, respectively. MPV was significantly associated with diagnosis (adjusted OR: 5.15, 95% CI: 1.090–23.7; p = 0.03). With the optimal cut-off value of 7.62 fL, MPV had 82% sensibility and 78% specificity for the differential diagnosis of TBM versus BM. Lower platelet counts, higher serum creatinine, higher white blood cell counts, and higher blood-cerebrospinal fluid glucose ratio were also predictive of BM. Conclusions: Platelet counts were lower and MPV was higher in patients with BM compared to patients with TBM. Platelet indices, available in routine bloodwork, could be useful in the early differential diagnosis of these entities. Key words: meningitis; mean platelet volume; inflammation; platelets; thrombocytopenia

Incremento de las citoquinas proteína quimiotáctica de monocitos-1 (MCP-1) y proteína inflamatoria macrofágica-1β (MIP-1β) en líquido cefalorraquídeo de pacientes con esclerosis lateral amiotrófica

Introducción: En la esclerosis lateral amiotrófica (ELA) se ha descrito recientemente la presencia de neuroinflamación. Sin embargo, no se ha definido el rol de citoquinas proinflamatrorias como la proteína quimiotáctica de monocitos-1 (MCP-1) y la proteína inflamatoria macrofágica-1� (MIP-1�) en ELA. En este estudio evaluamos niveles de MCP-1 y MIP-1� en líquido cefalorraquídeo (LCR), analizando su participación en la duración y gravedad de la ELA. Métodos: En 77 pacientes con ELA definida y 13 sujetos controles, se comparó el nivel de citoquinas MCP-1 y MIP-1� en LCR. Se analizaron estos niveles con relación a la duración de la ELA ( 12 meses) y a la gravedad de esta determinada mediante el puntaje obtenido al ingreso en la escala funcional estratificada de la ELA ( 30 puntos). Resultados: En los 77 pacientes con ELA, se encontraron aumentados los niveles de MIP-1� (4,69 pg/ml vs. 10,68 pg/ml, p < 0,0001) y MCP-1 (160,95 pg/ml vs. 234,89 pg/ml, p = 0,011) en comparación con sujetos controles. No se observó diferencia de los niveles de estas citoquinas con la duración o la gravedad de la enfermedad. Sin embargo, observamos una correlación positiva significativa entre MIP-1� y MCP-1 en pacientes con ELA. Conclusiones: El aumento de MIP-1� y MCP-1 sugiere que estas citoquinas parecen tener unefecto sinérgico en la patogénesis de la ELA. Sin embargo, en nuestra cohorte no se asociaroncon la duración o la gravedad de la ELA

Autonomic symptoms in hypertensive patients with post-acute minor ischemic stroke

Background Most studies regarding autonomic dysfunction in ischemic stroke are limited to heart rate and blood pressure changes during the acute phase. However, there are few data on quantitative assessment of autonomic symptoms. We sought to assess autonomic symptoms in hypertensive ischemic stroke patients. Methods In 100 hypertensive patients (45 with symptomatic ischemic stroke (6 months after stroke onset) and 55 without stroke), we assessed autonomic symptoms using the Scale for Outcomes in Parkinson disease-Autonomic (SCOPA-AUT). Results The age (mean ± standard deviation) for the stroke group was 66 ± 12 and 63 ± 15 for the without stroke group (P = 0.8). Orthostatic hypotension occurred in 3.6% of the stroke group and 4.4% in the group without stroke. The total SCOPA-AUT score was higher in the stroke group compared with the group without stroke (P = 0.001). Domain scores for gastrointestinal (P = 0.001), urinary (P = 0.005) and cardiovascular (P = 0.001) were higher in the stroke group. No differences were found when comparing the total SCOPA-AUT scores for stroke subtypes (P = 0.168) and for lateralization (P = 0.6). SCOPA AUT scores were correlated with depression scores (P = 0.001) but not with stroke severity (P = 0.2). Conclusion Autonomic symptoms, especially, gastrointestinal, urinary and cardiovascular function, were significantly increased in hypertensive patients with minor ischemic stroke. Symptoms were associated with depression but not with the characteristic of the stroke

1,25-dihydroxyvitamin D and PTHrP mediated malignant hypercalcemia in a seminoma

Background: Seminomas have been rarely associated with malignant hypercalcemia. The responsible mechanism of hypercalcemia in this setting has been described to be secondary to 1,25-dihydroxyvitamin D secretion. The relationship with PTHrP has not been determined or studied. The aim of this study is to describe and discuss the case and the pathophysiological mechanisms involved in a malignant hypercalcemia mediated by 1,25-dihydroxyvitamin D and PTHrP cosecretion in a patient with seminoma. Case presentation: A 35-year-old man was consulted for assessment and management of severe hypercalcemia related to an abdominal mass. Nausea, polyuria, polydipsia, lethargy and confusion led him to the emergency department. An abdominal and pelvic enhanced CT confirmed a calcified pelvic mass, along with multiple retroperitoneal lymphadenopathy. Chest x-ray revealed “cannon ball” pulmonary metastases. The histopathology result was consistent with a seminoma. Serum calcium was 14.7 mg/dl, PTH was undetectable, 25-dihydroxyvitamin D was within normal values and PTHrP and 1,25 dihydroxyvitamin were elevated (35.0 pg/ml, and 212 pg/ml, respectively). After the first cycle of chemotherapy with bleomycin, etoposide and cisplatin, normocalcemia was restored. Both PTHrP and 1,25-dihydroxyvitamin D, dropped dramatically to 9.0 pg/ml and 8.0 pg/ml, respectively. Conclusion: The association of seminoma and malignant hypercalcemia is extremely rare. We describe a case of a patient with a seminoma and malignant hypercalcemia related to paraneoplastic cosecretion of 1,25-dihydroxyvitamin D and PTHrP. After successful chemotherapy, calcium, PTHrP and 1,25-Dihydroxyvitamin D returned to normal values

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion

Hepatoprotective effect of commercial herbal extracts on carbon tetrachloride-induced liver damage in Wistar rats

Background: The antioxidant and anti-inflammatory effects of arbutin protect against a number of diseases. Objectives: The present study evaluated the protective effect of arbutin against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Methods: Sixty-three Wistar rats were divided into nine groups. Groups I and II were the normal control groups. Group III, the hepatotoxic group, was given CCl4. Groups IV, VI, and VIII received different dosages of arbutin along with CCl4. Groups V, VII, and IX were administered different dosages of arbutin. The albumin content, total protein, and bilirubin were assayed to determine their serum and antioxidant levels; lipid peroxidation was assessed in the serum and liver tissue. Histological studies were carried out to confirm the biochemical results. Results: Treatment with CCl4 for 28 d decreased the levels of total protein and albumin and increased the level of bilirubin and lipid peroxidation. Arbutin treatment raised the level of albumin and lowered the lipid peroxidation to normal levels. Necrosis and fibrosis were observed in the liver tissue of CCl4-injected rats, and the administration of arbutin had a protective effect on the liver tissue. Conclusions: The results of this study showed that arbutin may protect the liver against CCl4-induced oxidative damage in rats. This hepatoprotective effect might be correlated with the antioxidant and free radical scavenger effects of arbutin