Role of retinol in protecting epithelial cell damage induced by Clostridium difficile toxin A

Vitamin A (retinol), a fat-soluble vitamin, is an essential nutrient for the normal functioning of the visual system, epithelial cell integrity and growth, immunity, and reproduction. Our group has investigated the effect of high doses of oral vitamin A on early childhood diarrhea in our prospective community-based studies from Northeast Brazil and found a beneficial role in reducing the mean duration but not incidence of diarrheal episodes. In this study, we explored the role of retinol supplementation in intestinal cell lines following Clostridium difficile toxin A (TxA) challenge. C. difficile is the most common anaerobic pathogen borne with antibiotic-borne diarrhea and pseudomembranous colitis. Since retinol is critical for the integrity of tight junctions and to modulate the cell cycle, we have focused on changes in transepithelial electrical resistance (TEER) in Caco-2, a more differentiated intestinal cell line, and on models of cell proliferation, migration and viability in IEC-6 cells, an undifferentiated crypt cell line, following TxA injury. In this model, retinol therapy reduced apoptosis, improved cell migration and proliferation, and prevented the reduction in TEER, following C. difficile TxA challenge in a glutamine-free medium. These results suggest the role of retinol in protecting intestinal epithelial barrier function from C. difficile TxA enterotoxic damage.     

Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver

The ability to identify, isolate, and transplant progenitor cells from solid tissues would greatly facilitate the treatment of diseases currently requiring whole organ transplantation. In this study, cell fractions enriched in candidate epithelial progenitor cells from the rat pancreas were isolated and transplanted into the liver of an inbred strain of Fischer rats. Using a dipeptidyl dipeptidase IV genetic marker system to follow the fate of transplanted cells in conjunction with albumin gene expression, we provide conclusive evidence that, after transplantation to the liver, epithelial progenitor cells from the pancreas differentiate into hepatocytes, express liver-specific proteins, and become fully integrated into the liver parenchymal structure. These studies demonstrate the presence of multipotent progenitor cells in the adult pancreas and establish a role for the liver microenvironment in the terminal differentiation of epithelial cells of foregut origin. They further suggest that such progenitor cells might be useful in studies of organ repopulation following acute or chronic liver injury.     

Antiparasitic properties of homoallylamines and related compounds

A study of some antiparasitic properties of several homoallylamines and related tetrahydroquinolines and quinolines, previously described, was carried out using in vitro activity assays against the epimastigote form of Trypanosoma cruzi and against Trichomonas vaginalis. Unspecific cytotoxicity against murine macrophages was also studied. Although the antichagasic and trichomonacidal activities are not comparable to those of the standard drugs, nifurtimox and metronidazole, some of the compounds exhibit an interesting specific antiparasitic activity.     

Stress cardiomyopathy in thromboembolic arterial disease.

Apical ballooning is a novel clinical entity reported in different contexts of physical and psychological stress, which is more common in middle-aged women. Of unknown etiology, the syndrome is characterized by a sudden and transient dilatation of the left ventricular apex in the absence of obstructive atherosclerotic coronary disease or evidence of myocardial necrosis, with total late recovery of ventricular function. The authors report the case of a 53-year-old woman who was admitted to the emergency room with left arm ischemia and low cardiac output, requiring ventilatory support. Left catheterization showed typical medial and apical myocardial dysfunction, with normal coronary arteries. Transesophageal echocardiography revealed a thrombus attached to the lower face of the aortic arch, which probably explained the thromboembolism of the arm but was unlikely to be the cause of the left ventricular dysfunction since there were no enzymatic or electrocardiographic signs of myocardial necrosis and normal wall motion was fully recovered.     

Endosonographic characteristics of perigastrointestinal lymphnodes studied ex-corpore.

OBJECTIVES: Assessment of morphological characteristics of lymphnodes studied ex-corpore by echoendoscopy--shape, sharpness of limits, echogenicity and dimensions--to categorize them either as metastatic or non-metastatic. MATERIAL AND METHODS: Fifty-four lymphnodes were studied. They were identified and studied by echoendoscopy in fresh surgical specimens of oesophagus, stomach and rectum. Eight nodal characteristics were evaluated. The data obtained were studied by multivariate analysis using the logistical estimate method in two different statistical models. RESULTS: In model 1, logistical estimate demonstrated that well-defined limits (WDL) of the lymphnodes and the association of hypoechogenicity and round shape were the most significant variables suggesting the presence of invasion. In model 2, the most significant variables were WDL, round shape and association of round shape with WDL. The first model had a high sensitivity of 93.1% and specificity of 68% whereas the second model had a greater specificity of 84%, with a slight fall in sensitivity. CONCLUSION: These models might have an application to clinical practice particularly in the pre-operative assessment of patients with oesophageal carcinoma, gastric carcinoma or rectal carcinoma.     

Transseptal left heart catheterization: usefulness of the intracavitary electrocardiogram in the localization of the fossa ovalis.

One of the major difficulties in left heart catheterization through the interatrial septum is to ensure that the Brockenbrough needle tip is correctly laid on the fossa ovalis floor (FOF), which is the only area where the puncture must be done. The difficulties may be enhanced in patients with atrial enlargement and subsequent distortion of the anatomical structures. In order to reduce the hazards of the septal puncture, an electrocardiographic mapping of the right atrial endocardium was performed using the Brockenbrough needle as an exploratory electrode in a group of 20 patients. When the tip of the needle was laid against the FOF, the endoatrial electrocardiogram (EAE) registered a slight or no injury curve, even when the pressure was tight enough to perforate the septum. On the contrary, the pressure on any other area of the muscular septum or atrial walls elicited a bizarre monophasic injury curve. The peculiar electrocardiographic response of the FOF to the pressure exerted by the Brockenbrough needle tip was a valuable aid to identify the area where the transseptal puncture must be done. In addition, the sudden changes in the P wave morphology immediately after the septal perforation, provided the first clue that the left atrium has been reached.     

Skin cancers and precancerous lesions in Parkinson's disease patients.

Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies.     

Abnormal movements in Rett syndrome are present before the regression period: a case study.

The suspicion of a diagnosis of Rett syndrome (RTT) is based on clinical criteria that are often not present in the first two stages of the disease, as many of its symptoms will appear at a later age. This sometimes postpones the genetic diagnosis and an early clinical intervention. We present the case of 19-months-old girl who came to the consultation because of an arrest of psychomotor development noticed 5 months earlier without change in sleep pattern, behavior, or social communication. In the observation of 1 hour videotape, she presented subtle stereotypic movements of the face and hands as well as repetitive dystonic posturing of her limbs. A genetic test confirmed the diagnosis of RTT, showing a truncating mutation in the MECP2 gene (R270X). This case confirms that stereotypic movement anomalies, albeit infrequent and subtle, are already present before the regression stage and while maintaining prehension and that, in addition, repetitive dystonic postures may occur. Recognition of these early movement disorders will improve clinicians' ability to perform an earlier diagnosis of RTT.