Immunization with PIII, a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, affects nitric oxide production by murine spleen cells

Nitric oxide (NO) is an important effector molecule involved in immune regulation and defense. NO produced by cytokine-activated macrophages was reported to be cytotoxic against the helminth Schistosoma mansoni. Identification and characterization of S. mansoni antigens that can provide protective immunity is crucial for understanding the complex immunoregulatory events that modulate the immune response in schistosomiasis. It is, then, essential to have available defined, purified parasite antigens. Previous work by our laboratory identified a fraction of S. mansoni soluble adult worm antigenic preparation (SWAP), named PIII, able to elicit significant in vitro cell proliferation and at the same time lower in vitro and in vivo granuloma formation when compared either to SEA (soluble egg antigen) or to SWAP. In the present work we report the effect of different in vivo trials with mice on their spleen cells ability to produce NO. We demonstrate that PIII-immunization is able to significantly increase NO production by spleen cells after in vitro stimulation with LPS. These data suggest a possible role for NO on the protective immunity induced by PIII.

Impacte de les mutacions del gen KRAS en pacients afectes de carcinoma no microcític de pulmó estadi IV i la seva relació amb altres biomarcadors

Hem analitzat la mutació KRAS i els seus subtipus en mostres tumorals de 114 pacients diagnosticats d’un carcinoma de pulmó estadi IV. Un 21,9% dels pacients presentaren la mutació de KRAS. Dels seus subtipus, la més freqüent va ser G12C (44%). Dels pacients tractats amb quimioteràpia s’obtingueren un 4,8% de respostes completes i un 47,6% presentaren progressió de la malaltia. S’observà una tendència significativa a menor temps fins a la progressió i major supervivència global acord amb el performance status i els nivells de RAP 80.Els pacients KRAS-G12C presentaren una tendència no significativa a major supervivència global respecte els altres.

Expression of inducible nitric oxide synthase in bovine corneal endothelial cells and keratocytes in vitro after lipopolysaccharide and cytokines stimulation.

PURPOSE: To determine whether bovine corneal endothelial (BCE) cells and keratocytes express the inducible form of nitric oxide synthase (NOS) after exposure to cytokines and lipopolysaccharide (LPS), and to study the regulation of NOS by growth factors. METHODS: Cultures of bovine corneal endothelial cells and keratocytes were exposed to increasing concentrations of LPS, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). At selected intervals after exposure, nitrite levels in the supernatants were evaluated by the Griess reaction. Total RNA was extracted from the cell cultures, and messenger RNA levels for inducible NOS (NOS-2) were measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Exposure of BCE cells and keratocytes to LPS and IFN-gamma resulted in an increase of nitrite levels that was potentiate by the addition of TNF-alpha. Analysis by RT-PCR demonstrated that nitrite release was correlated to the expression of NOS-2 messenger RNA in BCE cells and keratocytes. Stereoselective inhibitors of NOS and cycloheximide inhibited LPS-IFN-gamma-induced nitrite release in both cells, whereas transforming growth factor-beta (TGF-beta) slightly potentiated it. Fibroblast growth factor-2 (FGF-2) inhibited LPS-IFN-gamma-induced nitrite release and NOS-2 messenger RNA accumulation in keratocytes but not in BCE cells. CONCLUSIONS: The results demonstrate that in vitro activation of keratocytes and BCE cells by LPS and cytokines induces NOS-2 expression and release of large amounts of NO. The high amounts of NO could be involved in inflammatory corneal diseases in vivo.

La ineficàcia de les disposicions testamentàries en el llibre IV del Codi civil de Catalunya

El llibre IV reconeix sols la possibilitat de nul•litat. La crisi convivencial posterior al testament comporta la ineficàcia. La manca originària o sobrevinguda d’hereu té conseqüències diferenciades. L’hereu contractual i l’intestat poden detreure la falcídia.

Pràctiques i rituals funeraris a Tàrraco i el seu ager (segles II aC-III/IV dC)

L’objectiu d’aquest projecte ha estat identificar i analitzar els rituals funeraris a celebrats als suburbis de Tàrraco i el seu territorium. Per tal d’assolir-lo hem revisat col•leccions de museus, arxius i informes arqueològics arribant a documentar 721 enterraments. A través de la recerca, hem estudiat les peculiaritats i els elements d’aixovar que les tombes presenten amb el suport de les fonts escrites. Hem detectat pràctiques rituals com ara libacions, sacrificis i objectes relacionats amb ofrenes funeràries a l’exterior de les tombes. Hem documentat certa una uniformitat general i repetiva pel que fa a la selecció dels aixovars funerari. No obstant això, hi ha algunes diferències sobretot en aixovars que provenen de les tombes d’individus morts prematurament (individus no casats, infants). També s’ha constatat una diferència sexual entre dones i homes pel que fa als objectes d’aixovar. Hem utilitzat l’evidència arqueològica i literària per tal de trobar el significat d’aquests artefactes quotidians que canvien de significat quan entren en contacte amb els morts. En revisar la informació procedent d’excavacions hem identificat espais rituals específics dins de la necròpolis com jardins funeraris i ustrina. Aquest estudi ha explorat la manera com l’arqueologia ens permeten identificar les pràctiques rituals dins les àrees funeràries. L’estudi de materials arqueològics documentats als estrats de freqüentació de les necròpolis ens ha permès detectar l’evidència material de la ritualitat.

Schistosomiasis mansoni in Bananal (State of São Paulo, Brazil): IV. Study on the public awareness of its risks in the Palha District

A rather high prevalence of mansoni schistosomiasis has been observed in some localities of Bananal, State of São Paulo, during the past decade. The highest prevalence of schistosomiasis was found in the Palha District; it was thus considered adequate for an evaluation of public awareness of the risks involved in acquiring schistosomiasis, a likely outcome of certain behavior patterns. We interviewed 542 district-dwellers. The 5-to-39 age-group constituted 65.5% of the whole sample. Concerning the infection, 69.2% had hearsay information; 46.1% know the infection; 69.6% know how it is acquired; 31.5% know about the symptoms and 57.1% know what can be done to avoid infection; 17.7% declared to have acquired the infection at least once in their lifetime; 62.3% reported total or partial immersion in collections of water of Bananal, once or twice a week, 53.9% of these for bathing or fishing. Although most (91.7%) households have treated running water, are connected to the sewage network or have septic tanks, 9% of the people interviewed use to defecate on the field. It became clear that the educational messages aimed at this population had not been adequate, having failed to fulfil any expectations. The local people received only piecemeal and subjective information about their problem. The control of schistosomiasis requires an integrated practice, which includes the analysis of macro-determinant factors, such as basic sanitation, habitation, education and health care. In short, we require a multidisciplinary vision of the mechanisms of transmission of the infection, which depends upon adequate planning and well trained personnel, intent on their educational work, to attain satisfactory results.

Small Bowel Bacterial Overgrowth is found in 71% of IBS patients and associated symptoms respond wel to Rifaximin in a phase IV trial

Background: The prevalence of small intestinal bowel bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS) ranges from 43% to 78% as determined by the lactulose hydrogen breath (LHBT) test. Although rifaximine, a non-absorbable antibiotic, has been able to decrease global IBS symptoms as well as bloating in placebo-controlled randomized trials, these results were not repeated in phase IV studies in daily clinical practice. Aim: To assess the prevalence of SIBO in an IBS cohort and to evaluate the treatment response in the IBS cohort affected by SIBO. Methods: Enrolled patients were diagnosed with IBS using the following criteria: fulfillment of the Rome III criteria, absence of alarm symptoms (anemia, weight loss, nocturnal symptoms etc), normal fecal calproectin, normal endoscopic workup including histology. Celiac disease was excluded by serology and/or duodenal biopsy. All patients underwent lactulose hydrogen breath testing (LHBT) for SIBO diagnosis. Patients with SIBO were treated with rifaximine tablets (400mg twice daily for 14 days). Both before and at week 6 after rifaximin treatment, patients completed a questionnaire, where the following criteria were assessed individually using 11-point Likert scales: the bloating, flatulence, abdominal pain, diarrhea, and overall well-being. Results: Hundred-fifty IBS patients were enrolled (76% female, mean age 44 ± 16 years), of whom 106 (71%) were diagnosed with SIBO and consequently treated with rifaximine. Rifaximine treatment significantly reduced the following symptoms as assessed by the symptom questionnaire: bloating (5.5 ± 2.6 before vs. 3.6 ± 2.7 after treatment, p <0.001), flatulence (5 ± 2.7 vs. 4 ± 2.7, p = 0.015), diarrhea (2.9 ± 2.4 vs. 2 ± 2.4, p = 0.005), abdominal pain (4.8 ± 2.7 vs. 3.3 ± 2.5, p <0.001) and resulted in improved overall well-being (3.9 ± 2.4 vs. 2.7 ± 2.3, p <0.001). Thirteen of the 106 treated patients were lost to follow-up (12%). The LHBT was repeated 2-4 weeks after rifaximine treatment in 65/93 (70%) patients. Eradication of SIBO was documented in 85% of all patients (55/65), whereas 15% of patients (10/65) tested positive for SIBO as determined by the LHBT testing. Conclusions: The results of our phase IV trial indicate that a high proportion of IBS patients tested positive for SIBO. IBS symptoms (bloating, flatulence, diarrhea, pain, overall well-being) were significantly diminished following a 2-week treatment with rifaximine. These results support the previous findings of randomized controlled trials that the presence of SIBO is associated with symptom generation in IBS patients and that reduction and/or elimination of SIBO may help to alleviate IBSassociated symptoms.

Treatment of symphysitis pubis with one unique iv injection of Ibandronate: report of two cases

Objective: Osteitis pubis is a noninfectious painful inflammatorydisorder of the symphysis pubis. Etiologic factors are numerous, themost common are: osseous extension of adductor, enthesis due tosport overuse, irritation after urological and abdominal procedures,and systemic inflammatory disorders in particularspondylarthropathies. Many cases are idiopathic. The symptomsconsist of regional chronic mechanical and sometime nocturnal pain.Diagnosis is usually confirmed by either bone scintigraphy or by MRI.There are no standard treatments but conservative approachesincluding rest and NSAIDS are generally recommended. In 2001, agood clinical and radiological response of three refractory cases with3 to 6 monthly perfusions of pamidronate was reported [1].Ibandronate is a much more powerful and long-lasting bisphosphonatethan pamidronate, and has not yet been reported in literature to ourknowledge in this indication.Patients and Methods: We present two cases of idiopathic origin:one woman (63 years old) and one man (36 years old).The symptomswere present >3 months in the first patient and one year in the second.The diagnosis was confirmed by MRI which showed bone edemaon both sizes of symphysis and in the second case bony erosionsadjacent to the joint were seen. Both cases failed to respond toconservative measures. Both patients received one single direct ivInjection of 3 mg of Ibandronate.Results: The injections resulted in a rapid (within a few days)resolution of pain that lasted more than 6 months in both patients.No side effects were observed. In the first case, an isotope bone scanperformed 4 months after the injection showed no residual uptake. Thesecond patient had a repeated MRI after 6 months. It demonstrated anattenuation of bone edema compared to the first MRI.Conclusion: IV Ibandronate may constitute a safe and effectivetreatment option for patients with refractory osteitis pubis.References1 Maksymowych WP, Aaron SL, Russell AS. Treatment of refractorysymphysitis pubis with intravenous pamidronate. J Rheumatol.2001;28(12):2754, 2001.

The effect of nitric oxide combined with fluoroquinolones against Salmonella enterica serovar Typhimurium in vitro

Two regulons, soxRS and marRAB, are associated with resistance to quinolones or multiple antibiotic in Salmonella enterica serovar Typhimurium. These regulons are activated by nitric oxide and redox-cycling drugs, such as paraquat and cause on activation of the acrAB-encoded efflux pump. In this study, we investigated the effect of nitric oxide (NO) alone and in combination with ofloxacin, ciprofloxacin, and pefloxacin against S. typhimurium clinical isolates and mutant strains in vitro. We did not observe synergistic effect against clinical isolates and SH5014 (parent strain of acr mutant), while we found synergistic effect against PP120 (soxRS mutant) and SH7616 (an acr mutant) S. typhimurium for all quinolones. Our results suggest that the efficiencies of some antibiotics, including ofloxacin, ciprofloxacin, and pefloxacin are decreased via activation of soxRS and marRAB regulons by NO in S. enterica serovar Typhimurium. Further studies are warranted to establish the interaction of NO with the genes of Salmonella and, with multiple antibiotic resistance.

Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin.

Chronic administration of recombinant human erythropoietin (rHuEPO) can generate serious cardiovascular side effects such as arterial hypertension (HTA) in clinical and sport fields. It is hypothesized that nitric oxide (NO) can protect from noxious cardiovascular effects induced by chronic administration of rHuEPO. On this base, we studied the cardiovascular effects of chronic administration of rHuEPO in exercise-trained rats treated with an inhibitor of NO synthesis (L-NAME). Rats were treated or not with rHuEPO and/or L-NAME during 6 weeks. During the same period, rats were subjected to treadmill exercise. The blood pressure was measured weekly. Endothelial function of isolated aorta and small mesenteric arteries were studied and the morphology of the latter was investigated. L-NAME induced hypertension (197 ± 6 mmHg, at the end of the protocol). Exercise prevented the rise in blood pressure induced by L-NAME (170 ± 5 mmHg). However, exercise-trained rats treated with both rHuEPO and L-NAME developed severe hypertension (228 ± 9 mmHg). Furthermore, in these exercise-trained rats treated with rHuEPO/L-NAME, the acetylcholine-induced relaxation was markedly impaired in isolated aorta (60% of maximal relaxation) and small mesenteric arteries (53%). L-NAME hypertension induced an internal remodeling of small mesenteric arteries that was not modified by exercise, rHuEPO or both. Vascular ET-1 production was not increased in rHuEPO/L-NAME/training hypertensive rats. Furthermore, we observed that rHuEPO/L-NAME/training hypertensive rats died during the exercise or the recovery period (mortality 51%). Our findings suggest that the use of rHuEPO in sport, in order to improve physical performance, represents a high and fatal risk factor, especially with pre-existing cardiovascular risk.

Freshwater snails and Schistosomiasis mansoni in the state of Rio de Janeiro, Brazil: IV - Sul Fluminense Mesoregion

In this paper, the forth of a series dealing with the survey of freshwater gastropods of the state of Rio de Janeiro, the results of collections carried out in the Sul Fluminense Mesoregion from 2000 to 2002 are presented and revealed the occurrence of 18 species: Antillorbis nordestensis; Biomphalaria glabrata; Biomphalaria peregrina; Biomphalaria straminea; Biomphalaria tenagophila; Drepanotrema anatinum; Drepanotrema cimex; Drepanotrema lucidum; Ferrissia sp.; Gundlachia ticaga; Gundlachia sp.; Heleobia sp.; Lymnaea columella; Melanoides tuberculatus; Physa acuta; Physa marmorata; Pomacea sordida and Pomacea sp. As to the snail hosts of Schistosoma mansoni the most frequent species was B. tenagophila, found in all municipalities surveyed, except Parati. Besides new records the present study extends the distribution of B. peregrina and B. straminea in the state. No specimens were found harbouring larval forms of S. mansoni although different kinds of cercariae had been observed. An account about the current schistosomiasis transmission sites in this Mesoregion is presented as well.

Nitric oxide induces the expression of the monocarboxylate transporter MCT4 in cultured astrocytes by a cGMP-independent transcriptional activation.

The monocarboxylate transporter MCT4 is a proton-linked carrier particularly important for lactate release from highly glycolytic cells. In the central nervous system, MCT4 is exclusively expressed by astrocytes. Surprisingly, MCT4 expression in primary cultures of mouse cortical astrocytes is conspicuously low, suggesting that an external, nonastrocytic signal is necessary to obtain the observed pattern of expression in vivo. Here, we demonstrate that nitric oxide (NO), delivered by various NO donors, time- and dose-dependently induces MCT4 expression in cultured cortical astrocytes both at the mRNA and protein levels. In contrast, NO does not enhance the expression of MCT1, the other astrocytic monocarboxylate transporter. The transcriptional effect of NO is not mediated by a cGMP-dependent mechanism as shown by the absence of effect of a cGMP analog or of a selective guanylate cyclase inhibitor. NO causes an increase in astrocytic lactate transport capacity which requires the enhancement of MCT4 expression as both are prevented by the use of a specific siRNA against MCT4. In addition, cumulated lactate release by astrocytes over a period of 24 h was also enhanced by NO treatment. Our data suggest that NO represents a putative intercellular signal to control MCT4 expression in astrocytes and in doing so, to facilitate lactate transfer to other surrounding cell types in the central nervous system. © 2011 Wiley-Liss, Inc.

Diagnostic and statistical manual of mental disorders : DSM-IV-TR.

Since the "DSM-IV(R)" was published in 1994, we've seen many advances in our knowledge of psychiatric illness. This "Text Revision" incorporates information culled from a comprehensive literature review of research about mental disorders published since "DSM-IV(R)" was completed in 1994. Updated information is included about the associated features, culture, age, and gender features, prevalence, course, and familial pattern of mental disorders. The "DSM-IV-TR(R)" brings this essential diagnostic tool up-to-date, to promote effective diagnosis, treatment, and quality of care. Now you can get all the essential diagnostic information you rely on from the "DSM-IV(R)" along with important updates not found in the 1994 edition. Stay current with important updates to the "DSM-IV-TR(R)": Benefit from new research into Schizophrenia, Asperger's Disorder, and other conditions Utilize additional information about the epidemiology and other facets of DSM conditions Update ICD-9-CM codes implemented since 1994 (including Conduct Disorder, Dementia, Somatoform Disorders) DSM-IV-TR(R), the handheld version of the "Diagnostic and Statistical Manual of Mental Disorders, "Fourth Edition, Text Revision, is now available for both Palm OS and PocketPC handhelds. This Text Revision incorporates information culled from a comprehensive literature review of research about mental disorders and includes associated features, culture, age, and gender features, prevalence, course, and familial pattern of mental disorders.This resource was contributed by The National Documentation Centre on Drug Use.

Triatoma rubrovaria (Blanchard, 1843) (Hemiptera - Reduviidae - Triatominae) IV: bionomic aspects on the vector capacity of nymphs

Triatoma rubrovaria has become the most frequently captured triatomine species since the control of T. infestans in the state of Rio Grande do Sul (RS), Brazil. The aim of this study was to evaluate aspects of the vectorial competence of T. rubrovaria using nymphs raised in laboratory under environmental conditions of temperature and humidity and fed on mice. The average developmental period of T. rubrovaria was 180.1 days. The percentage of defecation shortly after feeding was still higher than previous studies in which samples of T. rubrovaria subjected to a slight starvation period before the blood meal were used. The obtained results support former indication that T. rubrovaria presents bionomic characteristics propitious to be a good vector of Trypanosoma cruzi to man. Therefore its domiciliary invasion process must be continuously monitored.