A phase I clinical trial of a multi-epitope polypeptide TAB9 combined with Montanide ISA 720 adjuvant in non-HIV-1 infected human volunteers.

A phase I clinical trial was performed to examine the safety and immunogenicity of a multi-epitope polypeptide comprising the central 15 amino acids of the V3 loop from six HIV-1 isolates. This protein called TAB9 was emulsified in Montanide ISA720 (Seppic, Paris) and administered intramuscularly at doses of 0, 0.2 and 1 mg to 24 healthy, HIV-1 seronegative adult males. Three immunisations were given at months 0, 1 and 6 in a randomised, double blind, placebo controlled clinical trial. The placebo was generally well tolerated. However, severe local reactions were observed in TAB9 vaccinated subjects after the second and third inoculations. Seven out of eight volunteers from the lower dose group showed moderate or severe local inflammation, while four out of eight subjects from the higher dose group developed granulomas and sterile abscesses. In general, the reactogenicity depended on the number of inoculations given and the dose of TAB9. Both doses were immunogenic, all immunised volunteers seroconverted and antibodies were broadly reactive against the V3 peptides included in the protein. All vaccine's sera reacted against gp120 in Western blot and 50% of them also neutralised at least one out of five laboratory isolates tested. No differences between doses were found. Anti TAB9 lymphoproliferative responses were observed, being more intense in the high dose group. Due to the strong local reactions that were found in this study, a change in the formulation will be required for further trials with this vaccine candidate in humans.     

A six-gene signature predicting breast cancer lung metastasis

The lungs are a frequent target of metastatic breast cancer cells, but the underlying molecular mechanisms are unclear. All existing data were obtained either using statistical association between gene expression measurements found in primary tumors and clinical outcome, or using experimentally derived signatures from mouse tumor models. Here, we describe a distinct approach that consists of using tissue surgically resected from lung metastatic lesions and comparing their gene expression profiles with those from nonpulmonary sites, all coming from breast cancer patients. We show that the gene expression profiles of organ-specific metastatic lesions can be used to predict lung metastasis in breast cancer. We identified a set of 21 lung metastasis-associated genes. Using a cohort of 72 lymph node-negative breast cancer patients, we developed a 6-gene prognostic classifier that discriminated breast primary cancers with a significantly higher risk of lung metastasis. We then validated the predictive ability of the 6-gene signature in 3 independent cohorts of breast cancers consisting of a total of 721 patients. Finally, we show that the signature improves risk stratification independently of known standard clinical variables and a previously established lung metastasis signature based on an experimental breast cancer metastasis model.     

Hyperhomocysteinaemia and folate deficiency in human immunodeficiency virus-infected children

BACKGROUND: Our aim was the detection of possible deficiencies of folate and cobalamin by the measurement of plasma total homocysteine (tHcy) in 69 human immunodeficiency virus (HIV) -infected children on antiretroviral treatment. We studied the relationship of these vitamins and methionine with tHcy values. MATERIALS AND METHODS: Plasma tHcy was determined by high-performance liquid chromatography with fluorescence detection, folate and cobalamin by competitive protein-binding chemiluminescence, and methionine by ion exchange chromatography. RESULTS: Significant differences were observed between tHcy concentrations in the HIV-infected patients and the reference values for children of similar ages (P < 0.0001). Folate values were significantly lower in HIV-infected children compared with our reference paediatric population (P < 0.0001), but cobalamin concentrations were similar between patients and reference values. A significantly negative correlation was found between tHcy and folate (r = - 0.596; P < 0.0001), and a significantly positive correlation between folate and the methionine : tHcy ratio (r = 0.501; P < 0.0001). Plasma tHcy was significantly higher (P = 0.008), while folate values and methionine : tHcy ratios were significantly lower (P = 0.007 and P = 0.042), in patients on protease inhibitor treatment than in patients on other antiretroviral therapies. CONCLUSIONS: The hyperhomocysteinaemia and low methionine : tHcy ratios observed in our group of HIV-infected children are probably a consequence of the low folate values, which interfere in the remethylation of homocysteine to methionine. Patients on protease inhibitor treatment showed significantly higher plasma tHcy concentrations, and lower folate values and methionine : tHcy ratios, compared with patients on other antiretroviral therapies. Hyperhomocysteinaemia is associated with the risk of premature stroke, which may have adverse consequences in the evolution of disease.     

Barcelona Smell Test - 24 (BAST-24): validation and smell characteristics in the healthy Spanish population

OBJECTIVES: Smell tests for clinical use have been developed in different countries, but no single test has gained general acceptance. The objectives of the study were to evaluate the smell outcomes in a Spanish population. METHODS: A prospective study on healthy volunteers (n = 120) without olfactory disturbances was performed. The volunteers were differentiated by gender, age, and smoking habit groups. We used a new olfactory test, the Barcelona Smell Test 24 (BAST-24) that consists of 24 odours scoring smell detection, identification, and forced choice. RESULTS: Volunteers showed the highest scores on smell detection for both 1st (99%) and 5th cranial nerve (98%) odours. Spontaneous smell identification (54.7% and 59.3%) and forced choice (72.2% and 42.6%) scores were lower than those of smell detection, for both 1st and 5th cranial nerves respectively. On smell identification, volunteers scored higher in the left than in the right nostril. Females had better smell identification for both 1st and 5th cranial nerves (62.8%, 66.7%) than males (50.3%, 58.8%). Non-smokers had higher scores (65%) than smokers (59%) on smell identification for the 5th CN. CONCLUSIONS: For smell identification, females, non-smokers, and left nostril had higher scores than males, smokers, and right nostril respectively. BAST-24 is a good and reliable method to test the olfactory function in the clinical practice.     

Nontuberculous mycobacteria infection after mesotherapy: preliminary report of 15 cases

BACKGROUND: Mesotherapy is an increasingly used technique which is currently causing several mycobacterial infections owing to contaminated substances being injected, and also to poor aseptic measures being held by nonprofessional practitioners. PATIENTS AND METHODS: We collected 15 cases of nontuberculous mycobacteria (NTM) infection after mesotherapy in a 6-month period. RESULTS: All patients were female with ages ranging from 19 to 52 years; the main substances injected were procaine and lecithin, and the time between mesotherapy and the appearance of the lesions varied between 1 and 12 weeks. Clinical lesions were mostly nodules and abscesses, which were localized in the abdomen and buttocks in the majority of cases. The main patient complaint was local pain but some presented with systemic symptoms such as fever and malaise. Biopsies reported granulomatous chronic inflammation in the majority of cases. Skin cultures were positive for NTM and Mycobacterium chelonae. DISCUSSION AND CONCLUSIONS: Mesotherapy not performed with quality controlled substances can be a predisposing factor for NTM infection.     

Novel anti-inflammatory properties of the angiogenesis inhibitor vasostatin

Endothelial cells are critically involved in the pathogenesis of inflammation, which is characterized by vasopermeability, plasma leakage, leukocyte recruitment, and neovascularization. Therefore, inhibitors of endothelial cell function could reduce inflammation. In this study, we evaluated the effects of the angiogenesis inhibitor vasostatin on inflammations induced by contact hypersensitivity reactions in mouse ears. Vasostatin-treated mice revealed significantly reduced edema formation, resulting from lower plasma leakage and inhibition of inflammation-associated vascular remodeling. Intravital microscopy studies of inflamed ears showed a decrease in the fraction of rolling leukocytes in vasostatin-treated mice, and Lycopersicon esculentum lectin-perfused ears revealed fewer leukocytes adherent to the vessel wall. The inflammatory infiltrate from vasostatin-treated mice was characterized by fewer CD8+ T cells, neutrophils, and macrophages compared to the saline-treated animals. In a modified Miles assay, vasostatin inhibited vascular endothelial growth factor-A-induced permeability, and inflamed ear tissues from vasostatin-treated mice expressed significantly reduced levels of the vascular destabilizer angiopoietin-2. These results reveal a previously unrecognized anti-inflammatory property of the angiogenesis inhibitor vasostatin, and suggest that vasostatin is a potential candidate drug for the treatment of inflammation.     

Murine experimental leprosy: Evaluation of immune response by analysis of peritoneal lavage cells and footpad histopathology

This study evaluated the immune response of nude and BALB/c mice inoculated in the footpads (FP) with Mycobacterium leprae after 3, 5 and 8 months. At each timepoint peritoneal cells, peripheral blood, FP and popliteal lymph nodes (PLN) were collected. Peritoneal cell cultures were performed to measure the H₂O₂, O₂^?, NO, IL‐2, IL‐4, IL‐10, IL‐12, IFN‐γ and TNF levels. Serum levels of anti‐PGL‐I antibodies were also quantified. The results showed that the infection was progressive in nude mice with bacterial multiplication, development of macroscopic lesions in the FP and presence of bacilli in the PLN at 8 months. In BALB/c mice, the infection reached a plateau of bacillary multiplication at 5 months and regressed at 8 months. Histopathological analysis of FP revealed a mononuclear inflammatory infiltrate with a large number of neutrophils at 5 months, with a higher number in nude mice. At 8 months, the number of neutrophils decreased and the infiltrate was predominantly mononuclear in both mouse strains. There was no H₂O_2, O₂^?, IL‐2, IL‐4, IL‐10 and IFN‐γ production in the course of infection in nude mice; however, in BALB/c, O₂^? and IL‐12 production was higher at 5 months and NO, IFN‐γ and TNF production was higher at 8 months when there was a decrease in the number of bacilli. The level of anti‐PGL‐I antibodies was higher in BALB/c mice. Thus, nude and BALB/c mice can be used as experimental models for the study of various aspects of leprosy.     

Trends in Pharmacy College Admission Test Requirements and Utilization Across Colleges and Schools of Pharmacy

Objective. To identify national trends among US pharmacy schools and colleges in their requirements for the Pharmacy College Admission Test (PCAT) and underlying rationales for not requiring pharmacy school applicants to take it.Methods. An electronic survey regarding the following was sent to all US pharmacy programs: current and future PCAT requirements for applicants, use of the PCAT or other means to assess applicants’ written communication skills, use of unofficial PCAT scores, and, if applicable, the rationale for not requiring applicants to submit PCAT scores. Data analysis was performed using Excel.Results. One hundred five (73%) of 144 schools and colleges of pharmacy responded to the survey. Twelve institutions discontinued the PCAT requirement between the 2018-2019 and 2019-2020 admissions cycles. The most commonly selected reason for discontinuation was a desire to increase pharmacy applications by reducing admission barriers. Pharmacy schools nationwide had concerns regarding high PCAT registration fees. The majority of pharmacy programs that used PCAT scores in their application process indicated that they always, often, or sometimes invited applicants for an interview before they had received the applicant’s official PCAT scores. The majority of pharmacy programs considered applicants’ PCAT writing score in making their admissions decisions. Other methods used included onsite essays and personal statements.Conclusion. At the time of this study the majority of US pharmacy schools required applicants to submit the PCAT scores before being considered for admission to pharmacy school; however, the use of this examination has declined nationally.