Relative weight of glucose, insulin and parathyroid hormone in the urinary loss of phosphate by chronically diabetic rats

This report deals with the relationships between glucose (G) and insulin on the tubular transport of phosphate (P) in chronically diabetic rats with high plasma levels of parathyroid hormone (PTH). Alloxan-induced diabetes leads to phosphorus depletion of the soft tissues. This phenomenon appears associated with weight loss and negative P balances caused by the increased urinary P excretion. Administration of 2 IU of insulin/100 g body weight (bw) to diabetic rats normalized their P balance and body weight. The effect of parathyroid function on the P metabolism of diabetic rats was investigated with balance experiments. Diabetic rats, intact or thyroparathyroidectomized (TPTX), have a greater urinary excretion of P than their controls. However, in control rats, the ratio intact:TPTX for urinary P is 1.0:0.76, showing the antiphosphaturic effect of parathyroid ablation. For diabetic animals, on the other hand, the ratio is 1.0:1.44. The simultaneous deficit of insulin and PTH thus quadruples the urinary P loss, instead of compensating for each other. The contribution of insulin deficit and hyperglycemia to the defect in tubular reabsorption (TRP) was investigated with clearance experiments (done on anesthetized, perfused rats). Five experimental groups were used: Controls (C), diabetics (D), controls+glucose (C+G), diabetics+insulin (D+I) and diabetics+insulin+glucose (D+I+G). All experimental groups showed a linear relationship between the TRP of P and G. The regression equation for C is significantly different (F=40.1, P<0.001) from that of D animals. The slope value measure the number of μmoles of P per μmol of G reabsorbed. For C and D rats, the ratio P:G approximates 1:4 and 1:20, respectively. The increase in P:G ratios represents the competition between both substrates for tubular resorption. Glycemias up to 11 mM (C and D+I) exist concurrent with the P:G ratio 1:4. Glycemias above 25 mM (D, C+G and D+I+G) produce a P:G ratio of 1:20. Fractional excretion of P (FEP) increased significantly in untreated, chronically diabetic rats (0.47± 0.12 vs controls=0.05±0.01, P<0.001). After a single intramuscular injection of insulin, the FEP decreased as a function of insulin levels. To normalize the FEP of diabetic rats in short-term experiments, insulin had to be administered in doses that produce plasma insulin levels 25 times greater than normal. The general information afforded by the present experiments shows that in untreated, chronically diabetic rats, insulin deficit plays an indirect role. The absence of PTH enhances the effect of hyperglycemia. The latter and the concurrent tubular overload of glucose are the cause of hyperphosphaturia in these animals. Received: 10 September 1996 / Accepted in revised form: 18 April 1997     

Towards cellular receptors for prions

Transmissible spongiform encephalopathies (TSE) are attributed to the conversion of the cellular prion protein (PrP(c)) into an abnormal isoform (PrP(sc)). This can be caused by the invasion of living organisms by infectious particles, or be inherited due to mutations on the PrP(c) gene. One of the most intriguing problems of prion biology is the inability to generate the infectious agent in vitro. This argues strongly that other cellular proteins besides those added in test tubes or found in cellular preparations are necessary for infection. Despite recent progress in the understanding of prion pathology, the subcellular compartments in which the interaction and conversion of PrP(c) into PrP(sc) take place are still controversial. PrP(c) interacts with various macromolecules at the cell membrane, in endocytic compartments and in the secretory pathway, all of which may play specific roles in the internalisation of PrP(sc) and conversion of PrP(c). A specific interacting protein required for the propagation of prions was originally proposed as a prion receptor, and later referred to as a ligand, a cofactor, protein X, or a partner. However, current studies indicate that PrP(c) associates with multi-molecular complexes, which mediate a variety of functions in distinct cellular compartments. It is proposed that a deeper understanding of the mechanics of such interactions, coupled to a better knowledge of the corresponding signalling pathways and ensuing cellular responses, will have a major impact on the prevention and treatment of TSE.     

B cell lymphoma of the thymus and salivary gland.

A case of primary low grade B cell lymphoma of the salivary gland associated with a low grade B cell lymphoma of the thymus and involvement of the skin is reported. The lesions in the salivary gland and in the thymus showed the typical features of a lymphoma arising from the mucosa associated lymphoid tissue (MALT) and comprised lymphatic follicles, centrocyte-like (CCL) cells and lymphoepithelial lesions. Immunohistochemistry and Southern blot analysis supported the hypothesis that these lesions can originate from the same cellular clone. These findings confirm the occurrence of low grade B cell MALT lymphoma in the thymus and the possibility of spread of MALT lymphoma to other mucosal sites.     

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.

     

Image-guided core breast biopsy: a suitable method for preoperative biological characterization of small (pT1) breast carcinomas

Multiple prognostic indicators, namely histological grade and immunostaining for estrogen (ER) and progesterone receptors (PgR), MIB 1, bc1-2, and p53, were retrospectively determined on preoperative core biopsies from 75 patients with pT 1 breast carcinoma. The association of the preoperatively evaluated factors with those on the corresponding resected tumors (i.e. nodal status, histological grade, presence or absence of vascular invasion and necrosis) was assessed. In univariate analysis, histological grade on resected tumors was significantly associated with histological grade on core biopsy, p53 expression, MIB1 immunostaining. An inverse association was found between postoperative histologic grade and ER, PgR, and bc1-2. Necrosis was significantly associated with grade, p53, MIB1, and inversely with ER, PgR, and bc1-2. Nodal involvement and vascular invasion were significantly associated with MIB1. In multivariate analysis, histological grade and ER were the only independent core biopsy variables associated with postoperative histological grade and necrosis, respectively. This study showed that image-guided core biopsy is a suitable method that can be used to reveal some characteristics of the tumor biology in a preoperative stage.     

Impact of hepatitis C virus infection on clinical features, quality of life and survival of patients with lymphoplasmacytoid lymphoma/immunocytoma

Background: The non-Hodgkins lymphoma (NHL) subgroup most frequentlyassociated with hepatitis C virus (HCV) infection is the lymphoplasmacytoidlymphoma/immunocytoma (Lp-Ic). We have assessed the impact of the infectionon the clinical features, quality of life and survival of HCV+ve Lp-Icpatients as compared to its impact in HCV–ve patients.Patients and methods: Seventy patients with Lp-Ic consecutively observedover a six-year period were studied. Clinical, virological andhistopathological features were recorded at diagnosis. Quality of life wasassessed using a scoring system including disease-related symptoms,performance status, working ability, hospital admissions and therapiesrequired.Results: Eighteen patients (26%) with HCV infection wereidentified. Significant differences between those patients and theHCV–ve group included number of symptomatic patients, Hb levels, serumprotein levels, entity of the IgM monoclonal component, number of patientswith cryoglobulins and with organ (liver, kidney) involvement, and entityand pattern of bone marrow infiltration. Survival rates were similar (P =0.8383), but the quality-of-life score was significantly worse for theHCV+ve patients (P = 0.002). All anti-HCV Ab+ve patients tested positive forHCV RNA; genotype 2ac was detected in a significant proportion of cases.Conclusions: This study confirms that HCV infection is present in aboutone-third of patients with Lp-Ic. HCV infection does not seem to affect theoverall survival of patients with Lp-Ic, but it affects the clinicalexpression of the disease, so that the overall quality of life of HCV+vepatients is significantly worse.     

Systemic review of trials on the use of tramadol in the treatment of acute and chronic pain

BACKGROUND: The purpose of the study was to verify the effectiveness of tramadol in the treatment of non-oncologic chronic pain, oncologic chronic pain and postoperative acute pain, applying the principles of meta-analytic analysis to randomized clinical trials (TCR). METHODS: I: Medline research of the TCR on the question in the period between 1989-1999, II: exclusion of single TCR through the question of Moore and Mcquay; calculation of the relative risk reduction (RRR), of the number needed to treat (NNT), of the odds ratio (OR) and of the typical odds ratio (TOR) of the trials which responded to characteristics of correct randomization and blindness, which expressed citation of the patients excluded from trial, and patients with measurable analgesic effectiveness (number of patients with reduction of the pain intensity 50%). RESULTS: 52 trials extracted from Medline: 10 on the treatment of non-oncologic chronic pain, 36 on the treatment of postoperative acute pain and 6 on the treatment of oncologic chronic pain. Responded fully to requirements: 8 studies (3 for non-oncologic chronic pain, 3 for postoperative acute pain and 2 for oncologic pain). The OR was 0.55 (-0.31/1.41); 0.44 (1.04/1.92) and 0.98 (0.5/1.46); the RRR was 0.26 (-0.19/0.71), 0.38 (0.15/0.61), 0.005 (0.19/0.20) and the NNT 6.6 (6.39/6.81), 5.26 (5.12/5.4), infinity in the 3 trials selected between those that concern the treatment of the nononcologic chronic pain (with TOR: 0.57 and confidence index: 0.23-0.9); the OR was 0.36 (1.06/1.78), 0.78 (-0.08/-1.64) and 1.12 (0.54/1.69); the RRR was 0.26 (-0.18/0.7), 0.07 (-0.2/0.35), -0.01 (-0.09/0.07) and the NNT 4.7 (4.42/4.58), 20 (19.8/20.20), infinity in the trials on the treatment of postoperative acute pain (with TOR: 0.4 and confidence index: -0.6-0.86); the OR was 0.53 (-0.67/1.73), 0.27 (-0.71/1.12); the RRR was 0.19 (-0.33/0.72), 0.35 (0.02/0.68) and the NNT 7.1 (6.78/7.42), 3.57 (3.37/3.76) in those that involved the treatment of oncologic chronic pain (with TOR: 0.49 and confidence index: 0.36-0.8). CONCLUSIONS: Although the short number of trials which can treated by the metanalytic technique the treatment with tramadol, compared comparison's to drugs (morphine, pentazocine, bupremorphine, etc.) determined a slight improvement in analgesic parameters or at least in analgesic effectiveness.