The inhibition of gastric ghrelin production by food intake in rats is dependent on the type of macronutrient

Ghrelin is a peptide mainly produced by the stomach that increases food intake and body weight. Ghrelin expression increases with fasting and is diminished by re-feeding, but although the expression of this hormone is regulated by the feeding state, the relation with diet composition is not yet well established. We have studied the inhibitory effect of the intake of two different macronutrients (fat and carbohydrates) on ghrelin production by the stomach in fasted rats, as well as the relation with another important signal in the regulation of energy balance, leptin. Ghrelin mRNA expression in the gastric mucosa was determined by Northern blotting, and leptin mRNA expression was determined by Northern blotting in the adipose tissue and by RT-PCR in the stomach; circulating and gastric concentrations of ghrelin and leptin were measured by enzyme immunosorbent assay and ELISA, respectively. Our results showed an increase in ghrelin mRNA levels in response to 14 h of fasting. Food intake for 20 min after the fast produced a decrease in ghrelin mRNA expression that was recovered in 45 min in rats that ate the fat diet, whereas levels remained low when rats ate the carbohydrate diet. Serum ghrelin followed a similar tendency. The decrease in ghrelin expression by feeding was associated with an increased expression of gastric leptin only when animals ate carbohydrates. We conclude that the inhibition of ghrelin production by the stomach after re-feeding of fasted rats is dependent on diet composition and can be related to the different satiating capacity of the ingested macronutrients, which is higher for carbohydrates than fat.     

Comparative analysis of aggregate shapes by digitized microscopic images. Application to hypertension

The main objective of the present work was to study modifications in RBC aggregate morphology by analyzing digitized microscopic images and compare them between healthy subjects and patients suffering from essential hypertension. Blood samples were obtained from normal subjects (n=30) and patients suffering from essential hypertension (n=20). RBC aggregate morphology was quantified using direct microscopic observation and numerical analysis of images. ASP (Aggregation Shape Parameter) defined as the ratio of the area of the projected image to its square perimeter was calculated. Other rheological parameters have been determined in order to establish the hemorheological profile of the studied hypertension states. ASP appears significantly higher (p<0.001) in patients suffering essential hypertension (0.69+/-0.11) than in normal control subjects (0.25+/-0.12). RBC aggregation is known to be responsible for the high increase in apparent blood viscosity at low shear rates. By compare ASP values with whole blood viscosity at low rate (2.30 s(-1)) a high correlation was formed between both parameters (Spearman coefficient was 0.8835 and p<0.001). The applied method is simple, direct and quantitative and provides a useful tool for measuring deviations of RBC aggregate morphology.     

Abnormalities of Peripheral Blood T Lymphocytes and Natural Killer Cells in Alcoholic Hepatitis Persist after a 3-Month Withdrawal Period

Present information about the behavior of the different lymphoid subsets in alcoholic hepatitis (AH), including cells displaying cyto-toxic activity, is scanty and contradictory. The aim of this study was to gain further insight into knowledge of the immunological abnormalities involved in AH and the possible role of ethanol (EtOH) consumption in these changes. We analyzed the distribution of a wide range of peripheral blood (PB) lymphoid subsets, both during active EtOH intake and after a 3-month withdrawal period, using multiple stainings with monoclonal antibodies and flow cytometry, as well as natural killer (NK) cytotoxic activity. AH patients entering the study were selected strictly; only those undergoing their first episode of AH with no other lesions at liver biopsy were enrolled. Regarding the alcohol intake period, the most striking finding was a significant increase of the absolute number of PB T cells affecting both CD4⁺ and CD8⁺ lymphocytes. These changes were associated with a higher expression of T-cell activation antigens, such as HLA DR and CD11c. Simultaneously, a significant increase in both NK cells (CD3⁻-^/ CD56⁺) and the cytotoxic T cells coexpressing the CD3 and the CD56 molecules together with an increased NK cytotoxic activity were observed. By contrast, the CD19⁺/CD5⁺ B-cell subset was significantly decreased. No significant changes were observed with EtOH withdrawal except in CD5⁺ B lymphocytes, which returned to normal values. Our results show that, in AH patients, a significant expansion of both activated T cells and NK lymphocytes occurs in the PB, which is associated with an increased NK cytotoxic activity. Interestingly these abnormalities persist during the withdrawal period.     

Identification of problems in the functioning of individuals with schizophrenia from the expert perspective: an Internet-based survey

Purpose: The purpose of the study was to identify aspects of functioning and related environmental factors that are relevant to schizophrenia from the perspective of health professionals experienced in treating individuals with this disorder using the International Classification of Functioning, Disability and Health (ICF).

Method: An international pool of experts from diverse health care disciplines was surveyed to identify problems in functioning experienced by individuals with schizophrenia and the environmental factors that impact their functioning. On the basis of established rules, all answers were translated to the ICF by two independent researchers.

Results: One-hundred and eighty-nine experts from all six World Health Organization regions identified 4776 meaningful concepts, of which 92% were linked to 347 different ICF categories. Of the 347 categories, 194 were second-level categories, 151 were third-level categories and 2 were fourth-level categories. Ninety-five second-level ICF categories, 43 third-level categories and 1 fourth-level category reached percentage frequency of at least 5%. The majority of the categories were attributed to body functions, activities and participation, and environmental factors.

Conclusions: Health professionals identified a wide range of problems in functioning that reflect the complexity and breadth of schizophrenia, specifically activity limitations and participation restrictions that are particularly relevant for individuals with schizophrenia. Knowing these functioning problems can guide the design of patient-oriented rehabilitation programmes.

• Implications for rehabilitation

• Schizophrenia may result in impaired functioning in multiple daily life activities. The International Classification of Functioning, Disability and Health (ICF) can help in identifying the needs and problems of these individuals.

• The reported list of ICF categories can facilitate a systematic application of the ICF in schizophrenia and can help to design and implement coordinated and patient oriented rehabilitation programmes with a biopsychosocial approach.

• According to health professionals surveyed, activity limitations and participation restrictions are broadly affected in this population and are highly influenced by neurocognitive and social cognitive deficits and environmental factors.

     

Chronic Alcoholism Is Associated With an Imbalanced Production of Th-1/Th-2 Cytokines by Peripheral Blood T Cells

BACKGROUND: In the present study, we analyzed, at the intracellular level, the pattern of cytokine secretion by the major CD4+ and CD8strong+ peripheral blood (PB) T-cell subsets in patients with chronic alcoholism, and we correlated it both with the ethanol (EtOH) intake status and with the presence or not of alcoholic liver disease. METHODS: For that purpose, a total of 30 chronic alcoholic patients, 10 without liver disease (AWLD group) and 20 diagnosed with alcoholic liver cirrhosis (ALC) were studied. In all cases, flow cytometric measurement of intracellular expression of interferon-gamma (IFN-gamma), interleukin (IL)-2, and IL-4 was performed on PB CD4+ and CD8strong+ T lymphocytes. RESULTS: After studying AWLD patients, we found increased numbers of both CD4+ and CD8strong+ PB T cells with detectable cytoplasmic levels of the IL-2 and IFN-gamma T helper (Th)-1-associated cytokines, the greater increase being observed for this latter cytokine (p<0.001 for CD4+ and p<0.01 for CD8strong+ T cells). Regarding ALC patients, the pattern of expression of intracellular cytokines by PB T cells was different depending on the status of EtOH intake at the moment of entering this study. Accordingly, as in AWLD patients, ALC individuals who were actively drinking also displayed increased numbers of both CD4+ and CD8strong+ T cells expressing Th-1-associated cytokines. However, in these patients, expression of IFN-gamma, although being significantly greater than that observed in control individuals (p<0.05), was significantly lower than that in AWLD patients (p<0.01 and p<0.05, for CD4+ and CD8strong+ T cells, respectively). After a withdrawal period of > or =1 yr, ALC patients did not show significant changes in the cytoplasmic expression of Th-1-associated cytokines compared with the control group; in contrast, these patients showed a marked increase on the proportion of CD4+ and CD8strong+ T cells expressing IL-4, a Th-2-associated cytokine (p<0.01). After considering the ratio between the number of T cells expressing Th- (IFN-gamma)- and Th-2 (IL-4)-associated cytokines in each individual, we found that there was a significant imbalance in this ratio, with a predominance of IFN-gamma-producing T cells over IL-4+ T lymphocytes during EtOH intake. CONCLUSIONS: Our results showed that in patients with chronic alcoholism, active EtOH intake is associated with a Th-1 pattern of cytokine production by PB T cells.     

Finding of vascular amyloid TTR in inferior nasal concha in a patient with FAP TTRVal30Met

We report the case of a female patient with familial amyloid polyneuropathy (FAP) who demonstrated TTR amyloid deposition in the inferior nasal conchal vessels.

To our knowledge this location has not been described previously in FAP; in addition, it was detected in a patient who had undergone successful liver transplantation (LTX) 4 years earlier.

The amyloid deposition was found incidentally during examination of a right nasal obstruction caused by a nonspecific inflammatory polyp. Small focal deposits of amyloid TTR were observed on deep thick walled vessels, contrasting with the massive deposition reported in neoformed vessels in amyloidomas. This amyloid was clearly deposited between the onset of FAP and LTX and had probably decreased since the graft.

If amyloid deposition is frequent in inferior nasal concha in FAP, this location could be a suitable biopsy site.     

Type I interferon and TNFalpha cooperate with type II interferon for TRAIL induction and triggering of apoptosis in SK-N-MC EWING tumor cells

Ewing's sarcoma is the second most common human bone tumor in childhood. Here, we investigated the sensitivity of the Ewing tumor cell line, SK-N-MC, to the apoptotic effect of type I (IFNalpha) and type II (IFNgamma) interferons and TNFalpha. We demonstrate that although IFNalpha and TNFalpha alone are unable to induce cell death, they act in synergy with IFNgamma to induce SK-N-MC cell apoptosis. The synergistic induction of apoptosis correlated with the synergistic induction of TNFalpha-related apoptosis-inducing ligand (TRAIL) mRNA and TRAIL protein synthesis as well as of TRAIL secretion. Preparations of inducer-free supernatants from SK-N-MC cells stimulated with combinations of cytokines were shown to be cytotoxic for untreated SK-N-MC cells. This cytotoxicity was partially inhibited by addition of TRAILR2/Fc fusion protein, indicating that the secreted TRAIL mediates, at least in part, the apoptotic effect displayed by the supernatants of stimulated SK-N-MC cells. We have shown that the presence of IFNgamma is required to allow the sustained expression of IRF1 in SK-N-MC cells stimulated by addition of IFNalpha or TNFalpha suggesting that IRF1 plays a role in the synergistic induction of apoptosis by combinations of cytokines. Furthermore, we have shown that inhibition of NF-kappaB activation contributes to the IFNgamma-mediated sensitization to the apoptotic effect of TNFalpha. To our knowledge, this is the first report showing that interferon/cytokine combinations are able to induce TRAIL gene expression and TRAIL protein synthesis and secretion in Ewing sarcoma-derived cells. We believe that the observations reported here might contribute to the development of alternative new approaches to the treatment of Ewing tumors resistant to conventional therapy.     

Termination of very early pregnancy by vaginal suppositories-(15S)-15-methyl prostaglandin F2 alpha methyl ester

A new approach to terminate very early pregnancy was tried on 49 healthy women who were proven to be pregnant from 31 to 47 days from their last menstrual period. All pregnancies were confirmed either by UCG or serum HCG-B subunit. (15S)-15-Methyl PGF_2a Methyl Ester in a suppository form was administered in two separate doses: 1.0 mg initial dose followed by 3.0 mg one hour later. Patients were kept under observation for 8 hours. Blood sampling for progesterone, HCG-B, and prostaglandin levels were assayed at 0 °, 30′, 1 °, 4 °, 8 ° and 14 days. Patients were re-examined at a two week follow-up visit. Pelvic examination and pregnancy tests were performed to confirm whether the pregnancy was successfully terminated. There were no significant changes in serums progesterone and HCG-B levels during the 8-hour observation period. Both levels declined significantly to very low levels at 14 days post-therapy, confirming the clinical impression of successful termination of pregnancy. Plasma prostaglandin levels rose as early as 30 minutes after initiation of therapy, peaked at 4 hours and declined gradually afterwards. Most side effects such as nausea, vomiting, diarrhea and cramps, although clinically manageable, were still bothersome. One patient experienced an episode of vasovagal syncope. The majority of patients required medical observation up to 6 hours. Clinical implications of this new approach of termination of very early pregnancy are discussed.