The newly identified anorexigenic adipokine nesfatin-1 in hemodialysis patients: Are there associations with food intake, body composition and inflammation?

Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-α and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16±0.07ng/mL) and healthy subjects (0.17±0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia.

Myofibroblastic inflammatory breast tumor and fibrosarcoma: a case report.

Myofibroblastic inflammatory tumors can occur in any human tissue. They are benign lesions and more common in young patients. We describe the case of a 41-year-old patient with a nodule measuring 2.5 x 1.5 cm in the superior lateral quadrant of the left breast. The pathological examination showed proliferation of the spindle cells in dense fascicles interspersed by colagen among frequent plasmocytes, lymphocytes and eosinophils, associated with scarce typical mitosis. In the same site ten years before the patient had undergone a nodulectomy and the diagnosis was a benign filloid tumor. The patient returned with a nodule in the surgical scar at follow-up and the incisional biopsy showed a malignant filloid tumor with a sarcomatous component. A mastectomy was performed.

The possible role of nesfatin-1 on appetite regulation in hemodialysis patients.

Studies on appetite hormones in chronic kidney disease (CKD) patients appear of interest since these compounds may be implicated in reduced appetite, loss of weight and/or malnutrition. Anorexia seems to be related to many hormones that act in central nervous system, like leptin, obestatin and others, and more recently, was discovered a hypothalamus secreted protein that conduces to a decrease on food intake and to an increase on energetic waste, called nesfatin-1. This peptide has been studied in diabetes, mean arterial pressure and cardiovascular function, anxiety- and/or fear-related responses and inflammation, but there are no studies about a possible relationship with CKD. Therefore, considering the negative impact of anorexia and malnutrition in morbidity and mortality of CKD patients and the interest in new treatments findings for dialysis population, this review will discuss recent information about nesfatin-1 and its possible role in CKD patients.

Chronic antigen ingestion protects ovalbumin sensitized mice from severe manifestation of Leishmania major infection.

In the present work, the development of experimental leishmaniasis was examined in sensitized BALB/c mice that were chronically fed with antigen. After an oral challenge with egg white solution, the ovalbumin (Ova)-sensitized mice showed an increase in serum anti-Ova IgE and IgG1 antibodies. Lesions induced by Leishmania major infection were reduced by the ingestion of Ova in sensitized mice, as assessed by reduced footpad growth, lower parasite loads and improved pathological outcome compared to sham sensitized mice. Moreover, such findings were connected to a shift to a Th1 response involving higher IFN-gamma production and serum levels of IgG2a anti-Leishmania antigens. The data appear to corroborate the suggestion that chronic ingestion of an antigen by sensitized mice modulates the immunological system through a shift in cytokine release, exhibiting a healing response and resistance to L. major infection.

A model of chronic IgE-mediated food allergy in ovalbumin-sensitized mice.

Food allergy is most frequently the result of IgE-mediated hypersensitivity reactions. Here, we describe a chronic model in which some of the intestinal and systemic consequences of continuous egg white solution ingestion by ovalbumin-sensitized eight-week-old BALB/c mice, 6 animals per group, of both sexes, were investigated. There was a 20% loss of body weight that began one week after antigen exposure and persisted throughout the experiment (3 weeks). The sensitization procedure induced the production of anti-ovalbumin IgG1 and IgE, which were enhanced by oral antigen exposure (129% for IgG1 and 164% for IgE, compared to sensitization values). Intestinal changes were determined by jejunum edema at 6 h (45% Evans blue extravasation) and by a significant eosinophil infiltration with a peak at 48 h. By day 21 of continuous antigen exposure, histological findings were mild, with mast cell hyperplasia (100%) and increased mucus production (483%). Altogether, our data clearly demonstrate that, although immune stimulation was persistently occurring in response to continuous oral antigen exposure, regulatory mechanisms were occurring in the intestinal mucosa, preventing overt pathology. The experimental model described here reproduces the clinical and pathological changes of mild chronic food allergy and may be useful for mechanistic studies of this common clinical condition.

A model of chronic IgE-mediated food allergy in ovalbumin-sensitized mice

Food allergy is most frequently the result of IgE-mediated hypersensitivity reactions. Here, we describe a chronic model in which some of the intestinal and systemic consequences of continuous egg white solution ingestion by ovalbumin-sensitized eight-week-old BALB/c mice, 6 animals per group, of both sexes, were investigated. There was a 20 percent loss of body weight that began one week after antigen exposure and persisted throughout the experiment (3 weeks). The sensitization procedure induced the production of anti-ovalbumin IgG1 and IgE, which were enhanced by oral antigen exposure (129 percent for IgG1 and 164 percent for IgE, compared to sensitization values). Intestinal changes were determined by jejunum edema at 6 h (45 percent Evans blue extravasation) and by a significant eosinophil infiltration with a peak at 48 h. By day 21 of continuous antigen exposure, histological findings were mild, with mast cell hyperplasia (100 percent) and increased mucus production (483 percent). Altogether, our data clearly demonstrate that, although immune stimulation was persistently occurring in response to continuous oral antigen exposure, regulatory mechanisms were occurring in the intestinal mucosa, preventing overt pathology. The experimental model described here reproduces the clinical and pathological changes of mild chronic food allergy and may be useful for mechanistic studies of this common clinical condition.

Frequency of Trichomonas vaginalis, Candida sp and Gardnerella vaginalis in cervical-vaginal smears in four different decades.

CONTEXT: Vaginitis is one of the principal motives that lead women to seek out an obstetrician or gynecologist. Bacterial vaginosis, candidiasis and trichomoniasis are responsible for 90% of the cases of infectious vaginitis. OBJECTIVE: To verify the frequency of the three main causative agents of vaginitis, Trichomonas vaginalis, Candida sp and Gardnerella vaginalis, in four different decades (1960's, 1970's, 1980's and 1990's). DESIGN: Retrospective. PLACE: A tertiary referral center. PARTICIPANTS: Patients attended to as gynecology and obstetrics outpatients at the Faculdade de Medicina do Triângulo Mineiro during the years 1968, 1978, 1988, 1998, taken as samples of each decade. MAIN MEASUREMENTS: Diagnoses of infection by Trichomonas vaginalis, Candida sp and Gardnerella vaginalis were gathered from 20,356 cervical-vaginal cytology tests on patients attended to as gynecology outpatients at Faculdade de Medicina do Triângulo Mineiro during the years 1968, 1978, 1988, 1998, representing the four decades. The results were grouped according to the age group of the patients: under 20, between 20 and 29, between 30 and 39, between 40 and 49, and 50 or over. Statistical analysis was done via the chi-squared (Mantel-Haentzel) test with a significance level of 5%. RESULTS: In 1968 infections by Trichomonas vaginalis and Candida sp were diagnosed in 10% and 0.5% of the cytology tests and in 1978, 5.1% and 17.3%, respectively (P < 0.0001). Infection by Gardnerella vaginalis could only be evaluated in the latter two decades. In 1988, 19.8% of the women had positive tests for Gardnerella vaginalis, which was the most frequent agent in that year, diminishing in the subsequent decade to 15.9% (P < 0.0001). Candidiasis was the most frequent infection in 1998, detected in 22.5% of the tests (P < 0.0001). In a general manner, all the infections were most frequent among younger patients, especially those aged under 20, in all decades, whereas infections were least frequent among patients aged 50 or over (P < 0.05). CONCLUSION: There was a reduction in the frequency of cervical-vaginal infection by Trichomonas vaginalis and an increase in the frequency of Candida sp over the four decades studied. All the infections were most frequent in patients aged under 20 years.

High laryngeal mask airway pressures resulting from nitrous oxide do not increase pharyngeal mucosal injury in dogs.

PURPOSE: During general anesthesia, nitrous oxide (N2O) diffuses rapidly into the air-filled laryngeal mask airway (LMA) cuff, increasing intracuff pressure. There is no clear correlation between LMA intracuff pressure and pressure on the pharynx. We have studied the effects of high LMA intracuff pressures secondary to N2O on the pharyngeal mucosa of dogs. METHODS: Sixteen mongrel dogs were randomly allocated to two groups: G1 (intracuff volume, 30 mL; n=8) breathed a mixture of O2 (l L x min(-1)) and air (l L x min(-1)) and G2 (intracuff volume, 30 mL; n=8) a mixture of O2 (l L x min(-1)) and N2O (l L x min(-1)). Anesthesia was induced and maintained with pentobarbitone. LMA cuff pressure was measured at zero (control), 30, 60, 90 and 120 min after #4 LMA insertion. The dogs were sacrificed, and biopsy specimens from seven predetermined areas of the pharynx in contact with the LMA cuff were collected for light (LM) and scanning electron microscopic (SEM) examination by a blinded observer. RESULTS: LMA intracuff pressure decreased with time in G1 (P <0.001) and increased in G2 (P <0.001). There was a significant difference between the groups (P <0.001). In both groups, the LM study showed a normal epithelium covering the pharyngeal mucosa and mild congestion in the subepithelial layer. There were no differences between the groups (P >0.10) or among the areas sampled (P >0.05). In both groups, the SEM study showed a normal pharyngeal mucosa with mild superficial desquamation. Few specimens in G1 and G2 showed more intense epithelial desquamation. CONCLUSION: High LMA intracuff pressures produced by N2O do not increase pharyngeal mucosal injury in dogs.

Widespread hematogenous metastases and Trousseau's syndrome in gastric adenocarcinoma.

A case of widespread hematogenous metastases and Trousseau's syndrome is reported in a 40 year-old white housewife with gastric cancer, presenting subdural hematoma, ecchymoses, epistaxis, stomach and uterine bleeding. After undergoing hematoma drainage, she was unsuccessfully treated with platelets, red blood cells, plasma cryoprecipitate transfusions, and antibiotics. Necropsy disclosed gastric ring-signet adenocarcinoma invading the serous layer, with massive disseminated intravascular coagulation and systemic neoplastic embolism. Multiple old and recent hyaline (rich in fibrin and platelets) microthrombi, and tumor emboli were observed in the bone marrow, meninges, liver, lungs, kidneys, lymph nodes, adrenals, thyroid, heart, pancreas, and ovaries (Krukenberg tumor).

Morphologic and morphometric evaluation of pancreatic islets in chronic Chagas' disease.

PURPOSE: Hyperglycemia and abnormal glucose tolerance tests observed in some patients with chronic Chagas' disease suggest the possibility of morphological changes in pancreatic islets and/or denervation. The purpose of this study was to describe the morphology and morphometry of pancreatic islets in chronic Chagas' disease. METHODS: Morphologic and computerized morphometric studies were performed in fragments of the head, body, and tail regions of the pancreas obtained at necropsies of 8 normal controls and 17 patients with chronic Chagas' disease: 8 with the digestive form (Megas) and 9 with the congestive heart failure form. RESULTS: The Megas group had a larger (p < 0.05) pancreatic islet area in the tail of the pancreas (10649.3 +/- 4408.8 micrometer2) than the normal control (9481.8 +/- 3242.4 micrometer2) and congestive heart failure (9475.1 +/- 2104.9 micrometer2) groups; likewise, the density of the pancreatic islets (PI) was greater (1.2 +/- 0.7 vs. 0.9 +/- 0.6 vs. 1.9 +/- 1.0 PI/mm2, respectively). In the tail region of the pancreas of patients with the Megas form, there was a significant and positive correlation (r = +0.73) between the area and density of pancreatic islets. Discrete fibrosis and leukocytic infiltrates were found in pancreatic ganglia and pancreatic islets of the patients with Chagas' disease. Trypanosoma cruzi nests were not observed in the examined sections. Individuals with the Megas form of Chagas' disease showed increased area and density of pancreatic islets in the tail of the pancreas. CONCLUSION: The observed morphometric and morphologic alterations are consistent with functional changes in the pancreas, including glycemia and insulin disturbances.

[Contribution to the morphologic diagnosis of lung adiaspiromycosis]. / Contribuição ao diagnóstico morfológico da adiaspiromicose pulmonar.

The diagnosis of adiaspiromycosis is usually based on lung sections stained by hematoxylin-eosin, periodic acid Schiff and methenamine silver. Authors describe the fungus aspect examined by mucicarmin, picro-sirius and Congo red methods, including polarized light microscopy. In doubtful cases, these methods could contribute to histopathological diagnosis of Emmonsia parva var crescens.

Pulmonary adiaspiromycosis: report of two cases.

Two cases of human pulmonary adiaspiromycosis are reported. Patients were 29 and 54-year-old males, farm workers, with "grippe-like" symptoms and radiographic findings suggestive of granulomatous interstitial disease. Transthoracoscopic and transbronchial biopsies were performed. Pulmonary function was measured by spirometry. One patient used ketoconazole. Possibility of misdiagnosed pulmonary adiaspiromycosis is emphasized.

Cyto-histological correlation of 219 patients submitted to surgical treatment due to diagnosis of cervical intraepithelial neoplasia.

CONTEXT: Cervical cytology continues to be the most appropriate method for investigating cervical neoplasia and its precursors. Greater diagnostic acuity is obtained by combining cytology, colposcopy and guided biopsy methods. OBJECTIVE: To analyze the diagnostic acuity of cyto- and histopathological exams and causes of diagnostic error. DESIGN: Retrospective study. SETTING: A public tertiary referral center. SAMPLE: Reports on 219 patients submitted to cone biopsy and/or hysterectomy due to diagnosis of cervical intraepithelial neoplasia (CIN) in the period between January 1982 and March 1997 were reviewed, comparing. MAIN MEASUREMENTS: Cytological and histological exams (guided biopsy and surgically-removed tissue). In cases of discordance, the cyto- and histological preparations were reviewed to try to evaluate the causes of errors. RESULTS: In 193 cases (88.1%) there was cyto-histological agreement but none in 26 (11.9%). Review of the discordant cases showed that in 2 (0.9%) there was invasion of the stromata to a depth greater than 3 mm, and in 7 (3.2%) microinvasion, unsuspected via cytology; in 2 (0.9%) microinvasion was suspected via cytology but not confirmed by the final histological exam; and in 15 (6.8%) there was disagreement about the degree of CIN. CONCLUSION: The principal causes of error in the cytological exam were the lack of reliable morphological criteria for microinvasion, absence of sampling of the squamocolumnar junction, and scarcity of neoplastic cells in the sample. As for the histological exam, the errors were related to inadequate technical processing and underestimation of focal lesions.

Novel features of serine protease active sites and specificity pockets: sequence analysis and modelling studies of glutamate-specific endopeptidases and epidermolytic toxins.

With a view to obtaining a better understanding of the structural determinants of P1 glutamate specificity in glutamate-specific endopeptidases (GSEs), the active sites and specificity pockets of such enzymes from Bacillus licheniformis (gse-bl), Bacillus subtilis (mpr) and Staphylococcus aureus (v8 protease) were modelled. This approach was extended to the epidermolytic toxins (ETs), responsible for the staphylococcal scalded skin syndrome. We identify a canonical structure for the S1 subsite, composed of H213 and T190, both of which we predict to interact directly with the P1 glutamate. The possible importance of R30 (for gse-bl and mpr) and of the N-terminus (for gse-bl, mpr and v8 protease) was also examined. In the case of mpr, a G193C substitution is predicted to participate in a novel disulphide bridge which stabilizes C193 in such a way as to maintain the oxyanion hole. In v8, the loss or substitution of several important structural components around D102 of the catalytic triad probably explains its reduced catalytic efficiency in comparison with other GSEs. In the case of the epidermolytic toxins K216 may be important for the previously reported phospholipase C-like activity, since the model predicts that it may stabilize the negative charge on the phosphonyl group.

A structural model for the glutamate-specific endopeptidase from Streptomyces griseus that explains substrate specificity.

We present a model for the three-dimensional structure of the glutamate-specific endopeptidase from Streptomyces griseus based on the crystal structures of other bacterial proteases of the trypsin family. For the first time a structural model is described which attempts to explain the basis of P1 glutamate specificity in serine proteases. Several important changes to the S1 pocket with respect to other members of the family of different specificity are described. Of particular interest is the presence of a histidine at position 213 and the substitution of Arg-138 by lysine. Other biochemical evidence concerning substrate preferences can be rationalized on the basis of the model.

[Gastric paracoccidioidomycosis. A case report and considerations on the pathogenesis of this disease]. / Paracoccidioidomicose do estômago. Relato de caso e considerações sobre a patogenia desta lesão.

The authors report an unusual case of fungal gastric lesion in a patient with the chronic form of paracoccidioidomycosis. For a period of 8 months the major symptoms of the patient were abdominal pain and body weight loss. The endoscopic evaluation of the upper gastrointestinal tract showed a partial gastrectomy made previously, a great and irregular ulcer in the stomach and a granulated aspect of the duodenal mucosa. A granulomatous process and Paracoccidioides brasiliensis were observed in the histopathological examination of the gastric and duodenal biopsy tissue. New endoscopic evaluation 4 months after treatment with sulfadiazine revealed healing of the gastric ulcer. It was suggested that abdominal lymph nodes involvement, duodenal infection and anatomical and atrophic alterations of the stomach were predisposing factors for the gastric paracoccidioidomycosis.

Fine needle aspiration of squamous cell carcinoma of the skin metastatic to the site of leukemic lymphadenopathy. A case report.

Metastasis of a cancer to another coexisting tumor is a very rare event. A case of primary squamous cell carcinoma of the skin metastatic to lymph nodes replaced by chronic lymphoid leukemia and diagnosed by fine needle aspiration is presented. To our knowledge, this peculiar case represents the first time that these two concurrent tumors were diagnosed by fine needle aspiration.