Serine proteases of Leishmania amazonensis as immunomodulatory and disease-aggravating components of the crude LaAg vaccine

We previously demonstrated that intradermal and intramuscular vaccination with Leishmania amazonensis promastigote antigens (LaAg) increases the susceptibility of BALB/c mice to cutaneous leishmaniasis. In this study, we investigated the role played by serine and cysteine proteases as disease-promoting components of LaAg. Mice were immunized by the intramuscular route with LaAg that was pre-treated with a pool of serine or cysteine protease inhibitors (SPi and CPi, respectively) prior to infection with L. amazonensis. Neutralization of either enzyme type reversed the disease-promoting effect of LaAg, as seen by the slower lesion development. However, the parasite burden was only effectively controlled in mice receiving SPi-treated LaAg. Protection was associated with diminished production of TGF-β and particularly IL-10 in response to parasite antigens by the lesion-draining lymph node cells of vaccinated mice relative to control. In vitro, soluble proteases isolated from LaAg (LaSP-Sol) directly activated IL-4, IL-10 and TGF-β production by immune cells. Like native LaAg, vaccination with LaSP-Sol primed mice to respond to parasite challenge with a strong Jones-Mote cutaneous hypersensitivity reaction, and increased susceptibility to infection. Furthermore, neutralization of serine but not cysteine proteases blocked the capacity of LaAg to sensitize mice for Jones-Mote reaction. Together, these results indicate that soluble serine proteases are key components of LaAg responsible for its disease-promoting immunity.     

Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release

Growth hormone-releasing peptides (GHRPs) are a class of small peptides that stimulate growth hormone (GH) release in several animal species, including the human. Moreover, GHRPs injected into the brain ventricles stimulate feeding in the rat. The aim of this study was to evaluate the GH-releasing properties of a series of novel GHRP analogs and the possible existence of functional correlations between the GH-releasing activity and the effects on feeding behavior. Two well-known hexapeptides, GHRP-6 and hexarelin, given s.c., dose dependently stimulated both GH release and feeding behavior in satiated rats. However, in a series of tri-, penta- and hexapeptide analogs of hexarelin, some compounds were active either on GH release or on eating behavior. Interestingly, even minor structural modifications resulted in major changes of the pharmacological profile. We conclude that GHRPs have orexigenic properties after systemic administration which are largely independent from the effects they exert on GH release.     

Coccidioidomycosis in hematopoietic stem cell transplant recipients.

Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States that can cause devastating disseminated infection in immunocompromised persons. Clinical coccidioidomycosis, which is caused by Coccidioides species, has been well characterized in patients who have had solid organ transplants, but it has rarely been described in patients who have received a hematopoietic stem cell transplant (HSCT). We report the experience of 121 consecutive HSCT recipients at a single tertiary care institution in an endemic area. One patient had fatal disseminated coccidioidomycosis after receiving an allogeneic transplant, and 2 patients had pulmonary infection before successful autologous HSCT; 1 of these 2 had a reactivation of coccidioidal infection after HSCT but was treated and survived. Coccidioidomycosis was not commonly identified in HSCT recipients, even in the endemic area. A prospective evaluation is required to address the optimal use of coccidioidal serologic tests, antifungal protocols, and secondary prophylaxis in these patients.     

Gestational age-specific growth parameters for infants born at US military hospitals.

BACKGROUND: Military hospitals currently use gestational age-specific growth curves based on data collected in Denver, Colo, from 1948 to 1961. A number of population and environmental factors and medical practice changes may make these curves nonrepresentative. OBJECTIVE: Determine if presently used growth curves represent norms for infants born in military hospitals and create new curves for use in military hospitals. METHODS: Data were collected from medical records of tertiary- and primary-care military hospitals. We created growth curves created for birth weight, length, and head circumference and compared these curves at gestational ages 23-42 weeks to previously published norms and to 1998 national vital statistics. Racial and ethnic differences between groups were compared. A retrospective analysis of blood-glucose measurements for healthy term infants was performed to identify potential safety issues. RESULTS: Significant increases in growth parameters were noted for infants born in military hospitals. Specific racial and ethnic groups within the military also had an increase when compared with these groups in the United States as a whole. Less than 1% of infants classified as large for gestational age (LGA) according by old standards but average for gestational age (AGA) according to new curves experienced hypoglycemia. CONCLUSION: Published growth curves may not represent infants born in military hospitals. Term infants born in military hospitals as a group and in racial and ethnic subgroups are larger than term infants born in US civilian hospitals. Prospective use of curves will help to validate their long-term applicability in military and civilian nurseries.     

Surgical management of breast cancer

OBJECTIVES: To review the surgical treatment options for breast cancer and breast reconstruction options following mastectomy. DATA SOURCES: Clinical and research articles, textbook chapters, and clinical practice. CONCLUSION: Advances have been made in the surgical treatment of breast cancer, and options for less invasive procedures are now available. Patients are often faced with difficult decisions when trying to choose the best treatment option. IMPLICATIONS FOR NURSING PRACTICE: Nurses play an integral role in providing patients with the physical, educational, and emotional skills necessary to help them make appropriate surgical decisions and return to optimal health after their treatment.     

Plastic biliary stent occlusion: factors involved and possible preventive approaches

Endoscopic biliary stenting is today the most common palliative treatment for patients suffering from obstructive jaundice associated with malignant hepatobiliary tumors or benign strictures. However, recurrent jaundice, with or without cholangitis, is a major complication of a biliary endoprosthesis insertion. Thus, stent removal and replacement with a new one frequently occurs as a consequence of device blockage caused by microbial biofilm growth and biliary sludge accumulation in the lumen. Factors and mechanisms involved in plastic stent clogging arising from epidemiological, clinical and experimental data, as well as the possible strategies to prevent biliary stent failure, will be reviewed and discussed.     

Detection by flow cytometry of ESAT-6- and PPD-specific circulating CD4+ T lymphocytes as a diagnostic tool for tuberculosis

BACKGROUND: The identification of mycobacteria represents the gold standard in the diagnosis of tuberculosis (TB), but it is not applicable in all patients, and immunological tests, such as the tuberculin skin test (TST), are not specific and sensitive enough. METHODS: By flow cytometry, we measured the CD4 T-cell response to purified protein derivative (PPD) and early secretory antigenic target-6 (ESAT-6) protein using the intracellular cytokine staining technique on whole blood samples obtained from active TB (n = 16), latent TB (n = 17), Bacille Calmette-Guérin (BCG)-vaccinated (n = 11) and healthy (n = 10) donors. All the patients were also tested with conventional TST. RESULTS: The identification by flow cytometry of PPD-specific T lymphocytes upon antigen stimulation of whole blood enables the discrimination of active TB, latent TB and BCG-vaccinated subjects from healthy individuals, whereas the ESAT-6 response discriminated active TB from healthy and BCG-vaccinated individuals. Moreover, this test enables identification of active TB patients who were negative on TST and to distinguish between TB and non-typical mycobacteria TB infections. CONCLUSIONS: The identification by flow cytometry of antigen-specific T lymphocytes upon antigen stimulation of whole blood has a better positive predictive value than TST, and could represent a further tool in the diagnosis of TB infection.     

Environmental stress factors affecting survival and virulence of Campylobacter jejuni

Enteric pathogens are constantly exposed to stressful conditions in their natural habitat in the host and even more in the extra-host environment, including food processing. The aim of this study was to evaluate the effect of selected environmental stress factors: temperature shift, starvation and atmospheric oxygen concentration on culturability/viability of two Campylobacter jejuni isolates. Additionally, after stress exposure, in an in vitro cell culture model using Caco-2 cells, the adhesion, invasion and intracellular survival of C. jejuni were studied. Nutrient insufficiency was the most powerful stress factor which significantly affected C. jejuni culturability and viability, as well as, adhesion and invasion properties. Temperature elevation induced a transient growth arrest, and temporary loss of pathogenic potential as indicated by impaired adhesion and invasion efficiency of C. jejuni. However, bacteria recovered within 24-48h inside the Caco-2 cells. Oxidative stress neither affected C. jejuni growth nor reduced the binding and invasion into Caco-2 cells. Only 5h oxygen exposure increased the invasion capability and intraepithelial survival of the clinical isolate. Modulation of C. jejuni virulence in response to environmental stress factors may have further implications in the pathogenesis of campylobacteriosis.