The role of cyclic‐AMP on arginase activity by a murine macrophage cell line (RAW264.7) stimulated with lipopolysaccharide from Actinobacillus actinomycetemcomitans

Aims: The aim of the present study was to determine the role of cyclic adenosine monophosphate (cAMP) on arginase activity in a murine macrophage cell line (RAW264.7 cells) stimulated with lipopolysaccharide (LPS) from Actinobacillus actinomycetemcomitans. Materials and methods: The cells were treated with A. actinomycetemcomitans LPS for 24 h. The effects of SQ22536 (an adenylyl cyclase inhibitor), ODQ (a guanylyl cyclase inhibitor), dibutyryl cAMP (a cAMP analog), 8‐bromo cyclic guanosine monophosphate (a cGMP analog), forskolin (an adenylyl cylase activator), and cycloheximide (a protein synthesis inhibitor) on arginase activity in A. actinomycetemcomitans LPS‐stimulated RAW264.7 cells were also determined. Arginase activity was assessed in LPS‐stimulated cells in the presence of 3‐isobutyl‐1‐methylxanthine (IBMX), siguazodan and rolipram [phosphodiesterase (PDE) inhibitors] as well as KT5720 [a protein kinase A (PKA) inhibitor]. Results: Arginase activity in A. actinomycetemcomitans LPS‐stimulated RAW264.7 cells was suppressed by SQ22536 but not ODQ. Enhancement of arginase activity was observed in the presence of cAMP analog or forskolin but not cGMP analog. Cycloheximide blocked arginase activity in the cells in the presence of cAMP analog or forskolin with or without A. actinomycetemcomitans LPS. IBMX augmented arginase activity in A. actinomycetemcomitans LPS‐stimulated cells. Rolipram (a PDE4 inhibitor) increased the levels of arginase activity higher than siguazodan (a PDE3 inhibitor) in the antigen‐stimulated cells. The effect of cAMP analog or forskolin on arginase activity in the presence or absence of A. actinomycetemcomitans LPS was blocked by the PKA inhibitor (KT5720). Conclusion: The results of the present study suggest that A. actinomycetemcomitans LPS may stimulate arginase activity in murine macrophages (RAW264.7 cells) in a cAMP‐PKA‐dependent pathway.     

Elastofibromatous polyp of the sigmoid colon--a case report and review of gastrointestinal elastofibromas.

Elastofibromatous change in the gastrointestinal tract is a rarely reported, usually polypoid lesion of unknown etiology with submucosal stromal change that may mimic amyloid deposition. The constituent amorphous material of the polyp stroma has distinctive features that permit an accurate assessment and diagnosis including: distribution of the material predominantly in the submucosa; distinctive fibrillar and granular appearance of the deposits; thick, irregular, haphazardly arranged bundles of elastic fibres positive for Verhoeff's elastic stain; ultrastructural fibres with an electron dense curvilinear or beaded appearance; lack of amyloid type vascular wall deposits; and lack of amyloid congophilia or crystal violet metachromasia. The clinical, light microscopic, histochemical and ultrastructural characteristics of this deposited material are reviewed in detail in the present report of a patient who presented with an asymptomatic polypoid lesion of the sigmoid colon. Other reported cases are summarized, and their clinical and pathological features are compared with the current case.     

Research note: HLA degenerate T-cell epitopes from Plasmodium falciparum liver stage-specific antigen 1 (LSA-1) are highly conserved in isolates from geographically distinct areas

Considerable effort is directed at the development of a malaria vaccine that elicits antigen-specific T-cell responses against pre-erythrocytic antigens of Plasmodium falciparum. Genetic restriction of host T-cell responses and polymorphism of target epitopes on parasite antigens pose obstacles to the development of such a vaccine. Liver stage-specific antigen-1 (LSA-1) is a prime candidate vaccine antigen and five T-cell epitopes that are degenerately restricted by HLA molecules common in most populations have been identified on LSA-1. To define the extent of polymorphism within these T-cell epitopes, the N-terminal non-repetitive region of the LSA-1 gene from Malaysian P. falciparum field isolates was sequenced and compared with data of isolates from Brazil, Kenya and Papua New Guinea. Three of the T-cell epitopes were completely conserved while the remaining two were highly conserved in the isolates examined. Our findings underscore the potential of including these HLA-degenerate T-cell epitopes of LSA-1 in a subunit vaccine.     

Immune Augmentation of Single Contact Hepatitis B Vaccine by Using PLGA Microspheres as an Adjuvant

The present study was aimed to replace the alum type adjuvant for hepatitis B vaccine. The hepatitis B vaccine was encapsulated in poly (DL-lactide-co-glycolide) microspheres by solvent evaporation technique. The formulated microspheres were characterized in terms of morphology, particle size analysis, in vitro release study and in vivo immune response in male Wistar rats. The FT IR spectrum illustrates the characteristics bands of poly (DL-lactide-co-glycolide) microspheres and hepatitis B vaccine at 1750 cm^-1 and 1650 cm^-1, respectively. The hepatitis B vaccine loaded poly (DL-lactide-co-glycolide) microspheres were able to release antigens till day 42. Significant enhancement of specific antibodies to HBsAg was produced till day 90 after a single administration of HBsAg encapsulated poly (DL-lactide-co-glycolide) microspheres. However, the conventional alum adsorbed hepatitis B vaccine was not found to produce any significant specific antibody levels till day 90 after a single dose. The results showed that poly (DL-lactide-co-glycolide) microspheres show potential as an adjuvant for hepatitis B vaccine.     

Fine needle aspiration cytology as an adjunct to core biopsy in the assessment of symptomatic breast carcinoma

INTRODUCTION: Core biopsy (CB) has now largely replaced fine needle aspiration cytology (FNAC) in the pre-operative assessment of breast cancer. We studied the contribution of FNAC, when done as an adjunct to CB, in cancer patients presenting symptomatically. PATIENTS: 112 patients had both CB and FNAC pre-operatively and subsequently had surgery (wide local excision or mastectomy). CB & FNAC were done clinically in half the patients and under ultrasound guidance in the majority of others. RESULTS: The complete sensitivity of FNAC was 90% and that of CB was 99%. Absolute sensitivity was 67% and 94%, respectively. CB was not suspicious of malignancy (B1) only in 1 patient in whom FNAC was suspicious (C3). In this patient there was a high degree of suspicion of breast cancer clinically & radiologically so a negative CB would not have been accepted even in the absence of FNAC. CONCLUSIONS: FNAC, when performed in addition to CB, does not provide useful additional information in symptomatic breast cancer patients.     

Environmental and biological monitoring in a lead acid battery manufacturing unit in India

An environmental and biological monitoring of a lead acid battery manufacturing unit was carried out to measure the respirable particulate matter, lead content in working atmosphere and blood lead levels of workers employed in different sections. The results showed high mean air lead concentration in buffing (1444.45 microg/m(3)), plate cutting (430.14 microg/m(3)) and pasting (277.48 microg/m(3)) sections. The mean blood lead levels of employees in these sections were also higher than the values prescribed by ACGIH.     

Amelogenesis imperfecta: enamel ultra structure and molecular studies

Amelogenesis imperfecta (AI) is a hereditary disorder resulting in generalized defects in the enamel. The case reported here is of a seven-year-old male child with yellow color of all his teeth. Two of his primary molars were extracted due to dental abscess with advanced root resorption. Histologically hypoplastic enamel layer, positively birefringent, generalized pitting, roughness with irregular general cracked borders were observed. Scanning electron microscope, revealed extensive irregular, disorganized rough superficial enamel layer. The enamel was irregularly decussate with filamentous prisms accompanied by small rounded formations. The morphological and histological examination of the tooth revealed that this patient has the features of AI. For genetic study blood sample were collected from the patient and PCR analysis revealed that there is no mutation in exons 1-7 of AMELX gene on the X chromosome of the patient. Hence, it is probable that the AI of this patient is not X-linked. It is more likely to be an autosomal mutation.     

Rifampicin antagonizes the effect of choloroquine on chloroquine-resistant Plasmodium berghei in mice

Chloroquine (CQ)-resistant Plasmodium falciparum appears to decrease CQ accumulation in its food vacuole by enhancing its efflux via an active membrane pump, which has been reported to be a P-glycoprotein-like transporter. Rifampicin (RIF) is a P-glycoprotein inhibitor and also has some antimalarial activity. It is hoped that a combination of choloroquine-rifampicin (CQ + RIF) would be advantageous in the treatment of CQ-resistant malaria. Swiss albino mice were inoculated with CQ-resistant P. berghei intraperitoneally, and studied for the effect of CQ versus the combination of CQ + RIF at various doses on the clearance of parasitemia, the survival of the mice, and the recrudescence of malaria. Paradoxically, RIF decreased the survival rate and rate of clearance of parasitemia and increased the rate of recrudescence significantly when combined with various doses of CQ. Our results indicated that RIF worsened the course of the disease, and we concluded that RIF should not be combined with CQ in the treatment of malaria.