Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

Juvenile Systemic Lupus Erythematosus in Portugal: Clinical and Immunological Patterns of Disease Expression in a Cohort of 56 Patients

Objective: To define the pattern of disease expression and to gain better understanding in patients with juvenile onset systemic lupus erythematosus (SLE) in Portugal. Methods: The features of unselected patients with systemic lupus erythematosus who had disease onset before the age of 18 years were retrospectively analysed in three Portuguese centres with Pediatric Rheumatology Clinic over a 24-year period (1987-2011). Demographic, clinical and laboratory manifestations, therapy and outcome were assessed. Results: A cohort of 56 patients with a mean age at disease onset of 12.6±4.04 years (mean±1SD) (range, 1.0-17.0 years) and a mean period of follow-up of 5.5±5.4 years. Forty six (82.1%) patients were female. The most common disease manifestations were musculoskeletal (87.5%), mucocutaneous (80.3%) and haematological abnormalities (75%). Lupus nephritis was diagnosed in 46.4% of patients and consisted of glomerular ne - phritis in all cases. Neuropsychiatric manifestations occurred in 21.4% but severe central nervous system complications were uncommon, as brain infarcts and organic brain syndrome in 4 (7.1%) patients. Antinuclear antibodies and anti-double stranded DNA were positive in most patients in (98.2% and 71.4% respectively), as well as low C3 and/or C4 were observed frequently (85.7%). Generally, most patients had a good response to therapy as demonstrated by a significant decreasing of SLEDAI score from disease presentation to the last evaluation. The SLEDAI at diagnosis, the maximum SLEDAI and the incidence of complications were significantly higher in patients with neurolupus and/or lupus nephritis. Therapy included oral steroids (87.5%), hydroxychloroquine (85.7%), azathioprine (55.4%), IV cyclophosphamide (28.6%) along with other drugs. Six (10.7%) patients were treated with rituximab. Long-term remission was achieved in 32%, disease was active in 68%, adverse reactions to therapy occurred in 53.6% and complications/severe manifestations in 23.2%. Two patients died, being active disease and severe infection the causes of death. Conclusions: This study suggests that in our patients the clinical and laboratory features observed were similar to juvenile systemic lupus erythematosus patients from other series. Clinical outcome was favourable in the present study. Complications from therapy were frequent. Objective: To define the pattern of disease expression and to gain better understanding in patients with juvenile onset systemic lupus erythematosus (SLE) in Portugal. Methods: The features of unselected patients with systemic lupus erythematosus who had disease onset before the age of 18 years were retrospectively analysed in three Portuguese centres with Pediatric Rheumatology Clinic over a 24-year period (1987-2011). Demographic,clinical and laboratory manifestations, therapy and outcome were assessed. Results: A cohort of 56 patients with a mean age at disease onset of 12.6±4.04 years (mean±1SD) (range, 1.0-17.0 years) and a mean period of follow-up of 5.5±5.4 years. Forty six (82.1%) patients were female. The most common disease manifestations were musculoskeletal (87.5%), mucocutaneous (80.3%) and haematological abnormalities (75%). Lupus nephritis was diagnosed in 46.4% of patients and consisted of glomerular ne - phritis in all cases. Neuropsychiatric manifestations occurred in 21.4% but severe central nervous system complications were uncommon, as brain infarcts and organic brain syndrome in 4 (7.1%) patients. Antinuclear antibodies and anti-double stranded DNA were positive in most patients in (98.2% and 71.4% respectively), as well as low C3 and/or C4 were observed frequently (85.7%). Generally, most patients had a good response to therapy as demonstrated by a significant decreasing of SLEDAI score from disease presentation to the last evaluation. The SLEDAI at diagnosis, the maximum SLEDAI and the incidence of complications were significantly higher in patients with neurolupus and/or lupus nephritis. Therapy included oral steroids (87.5%), hydroxychloroquine (85.7%), azathioprine (55.4%), IV cyclophosphamide (28.6%) along with other drugs. Six (10.7%) patients were treated with rituximab. Long-term remission was achieved in 32%, disease was active in 68%, adverse reactions to therapy occurred in 53.6% and complications/severe manifestations in 23.2%. Two patients died, being active disease and severe infection the causes of death. Conclusions: This study suggests that in our patients the clinical and laboratory features observed were similar to juvenile systemic lupus erythematosus patients from other series. Clinical outcome was favourable in the present study. Complications from therapy were frequent.

Idiopathic Hypocomplementaemic Tubulointerstitial Nephritis

Background: Tubulointerstitial nephritis (TIN) is a common cause of kidney injury typically seen in association with drug exposure, infection or autoimmune diseases. However, TIN with interstitial immune complex deposition, without glomerular injury, is rarely observed. Case: We report a case of a 64-yearold Indian woman admitted for dialysis-requiring renal failure, without involvement of other organs. Urinalysis showed blood 3+ and 24h proteinuria of 1.5 g. Renal ultrasound revealed normal sized kidneys with loss of parenchymal-sinus differentiation. Laboratory tests disclosed low C3, positive ANA but negative anti-dsDNA, SSA and SSB. Serum protein electrophoresis was normal. The renal biopsy showed tubulointerstitial nephritis with positive immunoglobulin staining involving the interstitium and tubular basement membrane with glomerular sparing. The patient started prednisolone (1mg/kg/day) without recovery of the renal function. Conclusion: Idiopathic hypocomplementaemic tubulointerstitial nephritis is a rare disease with few cases described in the literature. To our knowledge this is the first case reported in Portugal.

Hand, Foot, and Mouth Syndrome in an Immunocompetent Adult: a Case Report

BACKGROUND: Hand, foot, and mouth syndrome (HFMS) is a common acute illness. It is characterized by mild clinical symptoms including fever, blisters, and sores in the mouth and on the palms and soles following a 3- to 7-day incubation period. This syndrome is rarely seen in adults. CASE PRESENTATION: A 35-year-old male Caucasian patient had a history of multiple episodes of acute pharyngitis, hypertension, hypercholesterolemia, and occasional abdominal pain. He presented with polyarthralgia in the knees and hands and odynophagia, followed by fever, oral mucosal aphthous lesions, and vesicles on the palms and soles. Three weeks after presentation, he was admitted to the emergency room with acute myocarditis. The in-hospital evaluation revealed positive serology for coxsackie A9 (1:160), positive anti-transglutaminase and anti-gliadin antibodies, normal immunoglobulins, and human immunodeficiency virus negativity. CONCLUSION: We herein describe a case of HFMS that was associated with coxsackie A9 infection complicated by acute myocarditis. Although an association between celiac disease and HFMS has not been described, this patient's immunologic disruption could have favored the development of infection and ultimately HFMS.

Sépsis Materna

Infections during pregnancy are prevalent. A small number of cases, however, may be life-threatening. Sepsis may be associated with multiple organ dysfunction and high mortality and it is one of the most common causes of direct maternal death often associated with the inability to recognize the severity of the illness. Long-term morbidity associated with maternal sepsis is significant and includes chronic pelvic inflammatory disease, chronic pelvic pain, bilateral tubal occlusion and infertility. The impact on neonatal mortality is also substantial, with over one million infection-related neonatal deaths eve - ry year. In the last few years, a vast number of clinical reviews of severe sepsis in pregnancy have been published, focusing on the characteristics of pregnant woman, the establishment of a specific treatment and the relevance of pregnancy surveillance by a multidisciplinary team. The treatment of sepsis is time-critical and requires early diagnosis, aggressive resuscitation, antibiotic administration and source control.

Cutaneous Infection by Different Alternaria Species in a Liver Transplant Recipient

Fungal invasive infections are rare in general population but are an emergent cause of infection in the immunocompromized population, especially in the solid organ transplant recipients. Herein the authors report a clinical case of a liver transplanted patient suffering a cutaneous co-existent infection with A. alternata as well as A. infectoria. To our knowledge this is the first case of cutaneous concomitant infection due to those two species reported not only in Portugal but also worldwide. The patient was treated with surgical excision of the lesions and oral itraconazol without relapse.

The PROP1 2-Base Pair Deletion Is a Common Cause of Combined Pituitary Hormone Deficiency

Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301–302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301–302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301–302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301–302delAG deletion suggests that rather than being inherited from a common founder, the 301–302delAG may be a recurring mutation.

Course of infection and histopathological lesions in mice infected with seventeen Trypanosoma cruzi strains isolated from chronic patients

Mice were infected with blood forms of 17 Trypanosoma cruzi strains recently isolated from chronic patients, which were dassified as of low, medium or high virulence on grounds of the prepatent period, parasitemia and mortality at the acute phase. A total of 212 mice were studied after 3, 6, 9 and 12 months of infection. In the chronic phase, intracellular parasites were detected in 11.0%,27.9%and 54.0,% of mice inoculated, respectively, with the low, medium and high virulent strains (r= 0.98, p < 0.005). Heart fibrosis was also related to virulence, affecting 5.7%, 11.6%and30.8% (r = 0.98, p < 0.001) of the mice inoculated with the above strains; a similar relationship was observed between intensity and frequency of the heart inflammatory reaction and the severity of infection at its early stage. Necrotizing arteritis was detected in 12.2% of the inoculated animals and this lesion was related to the infection duration rather than to strain characteristics. Inflammatory lesions and tissue parasitism were stable within the period of observation, whereas fibrosis was Progressive. The findings suggest that mice may reproduce heart lesions resembling human pathology and that organ damage apparently depends on the parasite virulence.

The PROP1 2-Base Pair Deletion Is a Common Cause of Combined Pituitary Hormone Deficiency

Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301-302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301-302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301-302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301-302delAG deletion suggests that rather than being inherited from a common founder, the 301-302delAG may be a recurring mutation.

The association of Schistosoma mansoni infection with hepatocellular carcinoma

The association of Schistosoma mansoni infection with hepatocellular carcinoma (HCC) was studied in Espirito Santo State, Brazil. Schistosoma infection was diagnosed by stool examinations or by histological finding at autopsy. HCC was diagnosed by biopsy, laparoscopy and biopsy or at autopsy. Among 45 cases of HCC six had Schistosoma mansoni infection (13.04%). The occurrence of Schistosoma infection among HCC HBs Ag positive or negative was similar (13.3 3% and 13.63% respectively). The chi squared comparison showed no significant differences between the frequency of schistosomiasis in patients with HCC and the frequency of Schistosoma infection among people living in the Espirito Santo State (5.9% among children of elementary school from all the counties of the State and 6.7% in people that attended medical care in Vitoria, the capital of the State). Therefore, the authors believe that the association of schistosomiasis mansoni with HCC may be casual, specially in areas where the Schistosoma mansoni infection is frequent.

Experimental paracoccidioidomycosis in the mouse. III. Histopathological and immunological findings after intravenous infection in the presence or absence of previous immunization

Fifty male white Swiss mice aged 4 weeks were inoculated with 5 x 10(5) viable yeast forms of Paracoccidioides brasiliensis (strain 18). Ten of these animals had been previously immunized with particulate P. brasiliensis antigenfor 4 weeks by intradermal injection. The controls consisted of 10 animals that were only immunized and 10 animals submitted to no treatment. The animals were sacrificed 2, 4, 7,11 and 16 weeks later. We studied: 1) the anti-P. brasiliensis delayed hypersensitivity response measured by the footpad test 24 hours prior to sacrifice; 2) the specific antibody production measured by double immunodiffusion in agar gel; 3) the histopathology of lungs, liver, spleen, adrenals and kidneys. We observed that: a) the immunized animals developed more intense cell-immune responses than the infected ones; b) infection reduced the cell- immune response of the immunized animals; c) intravenous infection of mice with P. brasiliensis was characterized by a systemic and progressive granulomatous inflammation. The animals infected after previous immunization showed less extensive lung inflammation, with smaller granulomas and fewer fungi. The results indicate that the present murine model mimics some findings of the human subacute form of paracoccidioidomycosis (systemic disease with depressed cellular immunity) and that the extrapulmonary immunization scheme was able to induce a certain degree of protection of the lung from infection with P. brasiliensis

Effects of betamethasone on the course of experimentai. Infection with Trypanosoma cruzi

In this experiment, the effect of betamethasone administered in the early post- acute infection of mice by Trypanosoma cruzi was studied. This drug was administered during 30 days after the 42nd day of infection in a dose of 0.15 mg/day. The betamethasone treatment did not cause fresh outbreaks of parasitemia and the histopathological findings in the chronic phase were not different from those in the control group. The higher cumulative mortality after treatment in the experimental group was due to superimposed bacterial infections. Outbred albino mice infected with low numbers ofY strain Trypanosoma cruzi trypomastigotes were not suitable models for Chagas' disease, since after 7 months of observation only mild histological lesions developed in all the animais. Prolonged betamethasone treatment of mice infected with low numbers o/Trypanosoma cruzi of the Y strain, during the post-acute phase did not aggravate the course of infection.