Immune modulation by cadmium and lead in the acute reporter antigen-popliteal lymph node assay.

Immune modulation by heavy metals may cause serious adverse health effects in humans, although the mechanisms involved are not well understood. Both cadmium and lead are important environmental and occupational toxins. Therefore, in the current study, the costimulatory/adjuvant effects and the T-cell-activating potential of these metals (i.e., CdCl2 and PbCl2), are examined. These immune-modulating properties are critical in the development of conditions such as allergy, hypersensitivity, and autoimmunity. Using the direct popliteal lymph node assay (PLNA) and reporter antigen-popliteal lymph node assay (RA-PLNA) both metals were examined individually for immunotoxicity. Mercury (i.e., HgCl2) was included for comparative purposes as its effects in the RA-PLNA are well documented. Seven days following a single footpad injection containing metal and/or RA (trinitrophenyl-ovalbumin [TNP-OVA] or TNP-Ficoll), BALB/c mice were sacrificed and the popliteal lymph nodes (PLNs) removed. PLN cellularity, TNP-specific antibody-secreting cells (ASCs), and lymphocyte subsets were assessed. All three metals strongly stimulated T- and B-cell proliferation and ASC production following coinjection with the RA TNP-OVA. In each case, ASC production was skewed towards the IgG1 isotype. In addition, all three metals induced IgG production to TNP-Ficoll (although relatively weakly in the case of Cd). These results show that each of these metals can provide adjuvant signals to promote lymphocyte proliferation and enhance adaptive immune responses to unrelated antigens. Skewing of immune responses towards T helper type 2 responses suggests that each of these metals can enhance allergic and hypersensitivity reactions to environmental antigens. Furthermore, the induction of IgG responses to TNP-Ficoll, a T-cell-independent antigen, indicates that each of these metals can activate neoantigen-specific T cells. T-cell activation by metals can lead to metal hypersensitivity and has been implicated in the development of autoimmunity. This is the first report of immune modulation by CdCl2 and PbCl2 in the RA-PLNA.     

Total pancreatectomy with islet autotransplantation: an overview

Pain control is one of the most challenging aspects in the management of chronic pancreatitis. Total pancreatectomy can successfully relieve the intractable abdominal pain in these patients but will inevitably result in insulin-dependent diabetes. Islet autotransplantation aims to preserve, as far as possible, the insulin secretory function of the islet cell mass thereby reducing (or even removing) the requirement for exogenous insulin administration after a total pancreactomy. Despite the relatively small number of centres able to perform these procedures, there are important technical variations in the details of their approaches. The aim of this review is to provide details of the current surgical practice for total pancreatectomy combined with islet autotransplantation, and outline the potential advantages and disadvantages of the variations adopted in each centre.     

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.     

Structured treatment and teaching of patients with Type 2 diabetes mellitus and impaired cognitive function--the DICOF trial.

BACKGROUND: Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self-management. AIM: To evaluate structured TTP for geriatric patients with impaired cognitive function. PATIENTS AND METHODS: A neuropsychological examination was performed on all patients over 54 years [n=102, age 68.6 +/- 8.7 years, diabetes duration 10.3 (0.03-35.4) years, HbA1c 10.3 +/- 1.7% (HPLC, Diamat, NR 4.5-6.3%), cognitive function 87.7 +/- 12.3 IQ points] who took part in TTP for insulin therapy. Patients with impaired cognitive function participated either in the standard TTP of Berger [n = 35, age 67.6 +/- 8.9 years, diabetes duration 9.9 (0.04-35.4) years, HbA1c 10.3 +/- 2.0%] or in the specialized structured geriatric DICOF-TTP [n=33, age 70.4 +/- 8.2 years, diabetes duration 10.4 (0.03-24.9) years, HbA1c 10.7 +/- 1.8%]. RESULTS: After TTP there were no differences in knowledge and ability for diabetes self-management (standard/DICOF: knowledge 11.0 +/- 2.6 vs. 12.2 +/- 2.7 points, P = 0.11; handling 14.9 +/- 3.3 vs. 15.9 +/- 2.5 points, P = 0.18). However, patients who took part in the DICOF programme showed better scores in satisfaction with the education programme [standard/DICOF 44.7 (31-57) vs. 52.5 (45-59) points, P < 0.001]. Six months later the DICOF participants showed better results regarding diabetes self-management (standard/DICOF: handling 12.5 +/- 4.1 vs. 15.9 +/- 3.1 points, P = 0.001). Both groups showed HbA1c decrease (8.3 +/- 1.4 vs. 8.5 +/- 1.3%, P=0.62) and similar incidence of acute complications. CONCLUSIONS: Elderly patients with impaired cognitive function should take part in specialized structured TTP. This leads to both better satisfaction with the education programme and an improved ability for diabetes self-management.