Bone disease in primary biliary cirrhosis: Lack of association with distal renal tubular acidosis

Background and Aims: Primary biliary cirrhosis (PBC) might be complicated by osteoporosis, whose etiology remains unknown but seems to be multifactorial. Prevalence rates of 30% to 60% for distal renal tubular acidosis (DRTA) have been reported in PBC patients, generally as incomplete DRTA. Although it is undisputed that a reduced bone mineral density (BMD) is the expected outcome among patients who have been suffering from longstanding chronic metabolic acidosis, it is unclear if incomplete DRTA is also associated with metabolic bone disease in PBC patients. The present study was undertaken to compare the BMD of PBC patients with and without DRTA.
Methods: The BMD of 23 PBC patients (11 with DRTA and 12 without), all with normal clearance of creatinine, was assessed by dual energy radiograph absorptiometry. The diagnosis of DRTA was made if the urine pH was above 5.4 in all samples after the oral acid overload, showing tubular inability to acidify urine in the presence of test-induced systemic metabolic acidosis.
Results: Densitometric signs of osteoporosis were found in 82% of DRTA cases and in 83% of patients without DRTA (difference not significant). There were no significant differences in BMD measurement, T and Z scores of patients with and without DRTA.
Conclusions: The present study could not support a correlation between the presence of DRTA and the bone loss observed in PBC patients.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

The immunodepressive effect of Friend virus. IV. Effects on spleen B lymphocytes.

Splenic immune responses having varying dependence on accessory cell co-operation have been studied after infection of mice with Friend virus. Infection has no effect on cell proliferation or antibody production in cultures stimulated with E. coli lipopolysaccharide. The response in vivo to type III pneumococcal polysaccharide is depressed only moderately. The response to sheep red blood cells is depressed severely both in vivo and in vitro. Depression in vitro is greatly reduced by co-stimulation with E. coli lipopolysaccharide. Depletion of potential suppressor lymphocyte populations by irradiation or adult thymectomy does not ameliorate depression of responses to sheep red blood cells or pneumococcal polysaccharide. Responses after adult thymectomy plus irradiation are not affected by the virus. Although it is known that macrophage and helper T-lymphocyte co-operation are not themselves impaired by infection, these results suggest that there is a direct relationship between severity of immune depression and dependence on co-operation. Implications for the action of the virus are discussed.     

Demonstration of immunoglobulin on the surface of thymus lymphocytes

Immunoglobulin molecules on the surface of mouse thymus cells have been shown by immunofluorescence. Ninety-five to 100 per cent of thymus lymphocytes were found to bind polyvalent rabbit anti-mouse immunoglobulin, although the density of the fluorescence was much less than that on the surface of B lymphocytes derived from the spleen.

Two purified antisera, an anti-IgM and an anti-kappa chain serum, also stained the cells.

The resynthesis of these immunoglobulin molecules in vitro was demonstrated after they had been removed with pronase.

     

Immune phagocytosis of Plasmodium yoelii-infected erythrocytes by macrophages and eosinophils.

Unstimulated peritoneal cells from C57Bl mice were allowed to phagocytose in vitro different mixtures of Percoll-separated parasitized and non-parasitized erythrocytes (PE and NPE) from the blood of mice infected with Plasmodium yoelii in the presence of immune and normal serum. Immune serum caused a significant enhancement of phagocytosis, and both the number of PE adhering to and/or ingested by 100 macrophages and the number of the latter cells engaged in phagocytosis was increased. The effect of immune serum was more marked when the ratio of PE/macrophages was 5--40/1, but was less at a ratio of 80/1, when considerable phagocytosis of PE occurred in the presence of normal serum. From 83--100% of the phagocytosed cells were parasitized erythrocytes, even when the ratio of PE/NPE was as low as 1/15. In the system used, macrophages were unable to discriminate between non-parasitized erythrocytes from infected mice and normal erythrocytes. Eosinophils were also observed to engage in phagocytosis of parasitized erythrocytes. Their activity was entirely dependent on immune serum and was never directed against non-parasitized red blood cells.