Interleukin 3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex "re-presentation" of exogenous antigen by tumor-infiltrating antigen-presenting cells.

We show that interleukin 3 (IL-3) enhances the generation of tumor-specific cytotoxic T lymphocytes (CTLs) through the stimulation of host antigen-presenting cells (APCs). The BALB/c (H-2d) spontaneous lung carcinoma line 1 was modified by gene transfection to express ovalbumin as a nominal "tumor antigen" and to secrete IL-3, a cytokine enhancing myeloid development. IL-3-transfected tumor cells are less tumorigenic than the parental cell line, and tumor-infiltrating lymphocytes isolated from these tumors contain increased numbers of tumor-specific CTLs. By using B3Z86/90.14 (B3Z), a unique T-cell hybridoma system restricted to ovalbumin/H-2b and implanting the tumors in (BALB/c x C57BL/6)F1 (H-2d/b) mice, we demonstrate that the IL-3-transfected tumors contain an increased number of a rare population of host cells that can process and "re-present" tumor antigen to CTLs. Electron microscopy allowed direct visualization of these host APCs, and these studies, along with surface marker phenotyping, indicate that these APCs are macrophage-like. The identification of these cells and their enhancement by IL-3 offers a new opportunity for tumor immunotherapy.     

Isolated hepatic tuberculosis: An uncommon presentation of a common culprit

Hepatic tuberculosis (HTB) is commonly encountered in patients with widespread miliary disease. Isolated affection of the liver is extremely rare. We present a case of a young woman who presented with a subacute afebrile hepatic failure. Investigations including a liver biopsy proved that the presentation was due to granulomatous hepatitis secondary to mycobacterial infection of the liver. It is important that tuberculosis (TB) be kept in mind especially in endemic areas even in atypical clinical scenarios by clinicians, radiologists, and pathologists. Use of anti-tuberculous drugs in such cases is usually successful and must be instituted early.     

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections.     

Clinical Efficacy of Subgingivally Delivered 1.2% Atorvastatin in Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: Atorvastatin (ATV) is a specific competitive inhibitor of 3‐hydroxy‐2‐methyl‐glutaryl coenzyme A reductase. Recently, statins have shown pleiotropic effects such as anti‐inflammation and bone stimulation. The aim of the present study is to investigate the effectiveness of 1.2% ATV as an adjunct to scaling and root planing (SRP) in the treatment of intrabony defects (IBDs). Methods: Sixty individuals were randomized into two treatment groups: SRP plus 1.2% ATV and SRP plus placebo gel. At baseline and 3, 6, and 9 months, clinical parameters, which included modified sulcus bleeding index, plaque index, probing depth (PD), and clinical attachment level (CAL), were recorded at baseline. Radiologic assessment of IBD fill was done using computer‐aided software at baseline and 6 and 9 months. Results: Mean PD reduction and mean CAL gain were greater in the ATV group than the placebo group at 3, 6, and 9 months. A significantly greater mean percentage of radiographic bone fill was found in the ATV group (35.49% ± 5.50%) compared to the placebo group (1.82% ± 1.32%) after 9 months. Conclusion: ATV as an adjunct to SRP can provide a new direction in the management of IBDs.     

Locally Delivered 1% Metformin Gel in the Treatment of Smokers with Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: Metformin (MF) (1,1‐dimethylbiguanide HCl) is one of the most commonly used oral antihyperglycemic agents for the treatment of type 2 diabetes mellitus. Recently, MF has been shown to have bone‐sparing properties. The present study is designed to investigate the effectiveness of MF 1% in an indigenously prepared, biodegradable, controlled‐release gel, as an adjunct to scaling and root planing (SRP) in treatment of vertical defects in smokers with generalized chronic periodontitis (CP). Methods: Fifty patients were categorized into two treatment groups: SRP plus 1% MF and SRP plus placebo. Clinical parameters were recorded at baseline and at 3 and 6 months; they included plaque index (PI), modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). At baseline and after 6 months, intrabony defect (IBD) fill was radiologically assessed using computer software. Results: Mean PD reduction and mean CAL gain were found to be greater in the MF group than the placebo group at all visits. Furthermore, a significantly greater mean percentage of bone fill was found in the MF group (26.17% ± 6.66%) than the placebo sites (3.75% ± 8.06%) (P <0.001). Conclusion: There was greater decrease in mSBI and PD and more CAL gain with significant IBD fill at vertical defect sites treated with SRP plus locally delivered MF, versus SRP plus placebo, in smokers with generalized CP.     

Efficacy of Subgingivally Delivered Simvastatin in the Treatment of Patients With Type 2 Diabetes and Chronic Periodontitis: A Randomized Double‐Masked Controlled Clinical Trial

Background: Simvastatin (SMV) is a specific competitive inhibitor of 3‐hydroxy‐2‐methyl‐glutaryl coenzyme A reductase. Recently, it has been reported that statins promote bone formation. The present study is designed to investigate the effectiveness of 1.2% SMV in an indigenously prepared, biodegradable, controlled‐release gel as an adjunct to scaling and root planing (SRP) in the treatment of patients with type 2 diabetes and chronic periodontitis (CP). Methods: Thirty‐eight patients were categorized into two treatment groups: SRP plus 1.2% SMV and SRP plus placebo. Clinical parameters were recorded at baseline before SRP and at 3, 6, and 9 months; they included modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). At baseline and after 6 and 9 months, radiologic assessment of intrabony defect (IBD) fill was done using computer‐aided software. Results: Mean PD reduction and mean CAL gain were found to be greater in the SMV group than the placebo group at 3, 6, and 9 months. Furthermore, significantly greater mean percentage of bone fill was found in the SMV group (32.64% ± 12.90%) compared to the placebo group (4.22% ± 9.75%) after 9 months. Conclusion: There was a greater decrease in mSBI and PD and more CAL gain with significant IBD fill at sites treated with SRP plus locally delivered SMV in patients with type 2 diabetes and CP.     

Role of nuclear hormone receptors in butyrate-mediated up-regulation of the antimicrobial peptide cathelicidin in epithelial colorectal cells

BACKGROUND AND AIMS: The human cathelicidin (LL-37) is one of the major antimicrobial peptides of the non-specific innate immune system in the intestinal tract. Altered expression has been associated with gastrointestinal disease. Recent studies demonstrated that butyrate induces LL-37 mRNA in colonic epithelial cells, however the underlying molecular mechanisms have not been elucidated. The objective of this study was to investigate the regulatory pathways involved in butyrate-induced up-regulation of LL-37. METHODS AND RESULTS: Treatment of Caco-2 and HT-29 cells with butyrate led to a time-dependent up-regulation of LL-37 mRNA expression as determined by semi-quantitative RT-PCR. Up-regulation of LL-37 mRNA by butyrate was subsequently followed by an increase in LL-37 protein expression as observed by immunofluorescence. Co-incubation of butyrate with a VDR, p38 MAPK, ERK 1/2 and TGF-beta1 receptor kinase inhibitor all reduced butyrate-mediated LL-37 mRNA up-regulation. In contrast, transfection of Caco-2 cells with a dominant-negative PPARgamma mutant vector did not affect butyrate-mediated up-regulation of LL-37 mRNA. CONCLUSION: Our results clearly demonstrate that butyrate-mediated up-regulation of LL-37 is influenced by several signalling pathways and receptors including MAPKs as well as VDR and TGF-beta1, but not by PPARgamma. These data may provide new opportunities in the treatment of gastrointestinal diseases.