Effects of chronic and acute protein administration on renal function in patients with chronic renal insufficiency

In 6 volunteers with normal renal function, we investigated the effects of various kinds of protein (soy, lactoprotein and beef) and various amounts of an intravenously administered amino acid solution on glomerular filtration (GFR) and effective renal plasma flow (ERPF). As for the protein-induced changes in renal function, rises in GFR and ERPF were lowest with soy protein, and highest with beef (baseline GFR, 110 +/- 5; soy, 122 +/- 5; beef, 131 +/- 5 ml/min/1.73 m2; mean +/- SEM). High doses of intravenous amino acids induced a rise in GFR comparable to that after beef (132 +/- 5 ml/min/1.73 m2). In a combined test a liquid mixed meal together with intravenously administered amino acids induced a comparable increase of the GFR (baseline 114 +/- 5 versus 129 +/- 5 ml/min/1.73 m2). When investigating 9 patients with chronic renal insufficiency after 4 weeks of low protein intake (LP) and after 4 weeks of high protein intake (HP), GFR and ERPF rose significantly under baseline conditions (GFR-LP41 +/- 9 versus GFR-HP 45 +/- 9 ml/min/1.73 m2, p less than 0.02; ERPF-LP 169 +/- 39 versus ERPF-HP 180 +/- 40 ml/min/1.73 m2, p less than 0.02; paired Wilcoxon). At the end of both dietary periods a comparable rise in renal function could be induced through acute stimulation (GFR-LP 20 +/- 5, GFR-HP 16 +/- 4; ERPF-LP 23 +/- 7, ERPF-HP 22 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of total body water and lean body mass from anthropometry, Watson formula, creatinine kinetics, and body electrical impedance compared with antipyrine kinetics in peritoneal dialysis patients

Background. Indirect methods such as anthropometry (A), Watson formula (W), creatinine kinetics (CK), and body electrical impedance (BEI) are increasingly applied to determine total body water (TBW) and lean body mass (LBM) in dialysis patients. These methods share the disadvantage that they have been validated for healthy men only. We studied which of these four commonly applied methods can best be used routinely in CAPD patients. Methods. TBW estimates obtained from A, W, CK, and BEI were compared with those obtained by a gold standard (antypirine distribution volume, ADV) in eight CAPD patients. In addition, several BEI equations to derive lean body mass (LBM) were compared with LBM estimated by ADV in order to determine which equation is the most valuable for the assessment of LBM by BEI in CAPD patients. Results. TBW as ADV was 41.4±6.6 (mean±SD) L. TBW estimated by W, A and CK underestimated ADV by a mean±SD of 2.3±13, 5±8.4 and 12.3±10.9% respectively. TBW as measured by BEI overestimated ADV by 2.5±8.8%. The correlation coefficients between ADV-TBW and TBW estimated by the indirect methods were r=0.88 (A), r=0.87 (BEI), r=0.82 (CK), and 0.68 (W). LBM estimated by ADV was 56.7±8.9 (mean±SD) kg; LBM by different BEI equations ranged from 49.9±7 to 58.1±10.7 kg. The correlation coefficient between LBM by ADV and LBM according to the various BEI equations ranged from 0.81 to 0.93. Conclusions. A and BEI: can be used to estimate TBW, but the considerable SD (or inaccuracy) makes individual predictions hazardous. Considering the correlation coefficients and difference between LBM by ADV and LBM according to different BEI equations, Deurenberg's formula can be advocated for use in the estimation of LBM by BEI.     

Immunological alterations found in mesothelioma patients and supporting experimental evidence

It is common knowledge that exposure to asbestos causes asbestos-related diseases, such as asbestosis, lung cancer and malignant mesothelioma, not only in people who have had long-term contact with asbestos in their work environment but also in residents living near factories that handle asbestos. Since the summer of 2005, these revelations turned into a large medical problem and caused and social unrest. We have focused on the immunological effects of both asbestos and silica on the human immune system. In this brief review, we introduce immunological alterations found in patients with malignant mesothelioma and describe the experimental background in which these were found. Analyzing the immunological effects of asbestos may improve our understanding of the biological effects of asbestos.     

A case of multiple skin metastases from gastric cancer successfully treated with docetaxel combined with doxifluridine

The results of treatment of gastric cancer with docetaxel have scarcely been reported. Combination chemotherapy of docetaxel and doxifluridine was administered to five patients with recurrent or unresectable gastric cancer in the authors' department, and the overall response rate was 40%. Among them, we report here a case of multiple skin metastases successfully treated with this chemotherapy. A 71-year-old man had already undergone total gastrectomy with splenectomy about one year previously because of advanced gastric cancer: type 3, tub2, se, n1, INF gamma, ly3(+), v1(+), stage IIIa. He was treated with adjuvant chemotherapy of low-dose FP (CDDP/5-FU) for two weeks, and thereafter 5-FU (200 mg/day orally) was administered. Skin metastases appeared on the right upper eyelid and the left femoral region, though no recurrent findings were detected by CT, US, and the like one year after operation. The combination chemotherapy of docetaxel and doxifluridine was administered because multiple skin tumors rapidly appeared on the back and the right upper eyelid region. These tumors disappeared after 3 weeks and he has had no recurrence more than one year after chemotherapy.     

Thromboxane synthetase inhibitors. I. Synthesis of some imidazolylarylmethanols and their inhibitory activity on platelet aggregation

Several imidazolylpyridinemethanols and imidazolylbenzenemethanols were prepared and evaluated for an inhibitory activity against arachidonic acid-induced platelet aggregation. The result shows that the arylmethanol moiety is essential for the activity and may correspond to the 15-OH group of prostagrandin H2 (PGH2). Among the compounds tested, 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid (XV) was found to have a potent inhibitory activity and a long duration of action. Structure-activity relationships are also discussed briefly.     

Persistence of N7-(2,3,4-trihydroxybutyl)guanine adducts in the livers of mice and rats exposed to 1,3-butadiene

Liquid chromatography (LC) in combination with tandem mass spectrometry (MS/MS) and stable isotope methodology was employed for the analysis of the N7-guanine (Gua) adducts derived from 1,2:3, 4-diepoxybutane (BDO2) a reactive metabolite of 1,3-butadiene (BD). Two diastereomeric forms of N7-(2,3,4-trihydroxybutyl)guanine (THBG) were identified in the livers of both mice and rats. One of the diastereomers [(+/-)-THBG] was formed by reaction of DNA with (+/-)-BDO2, and the other diastereomer (meso-THBG) was formed by reaction of DNA with meso-BDO2. There was significantly more (+/-)-THBG and meso-THBG in the liver DNA of the mice when compared with those of the rats during the 10 days of exposure to BD and the 6 days of postexposure that were monitored. There was a 2-fold excess of (+/-)-THBG over meso-THBG in the rat liver at all the time points. In the mouse liver after 10 days of exposure to BD, the (+/-)-THBG (3.9 adducts/10(6) normal bases) was also present in an almost 2-fold excess over meso-THBG (2.2 adducts/10(6) normal bases). However, 6-days after exposure to BD, (+/-)-THBG (1.2 adducts/10(6) normal bases) and meso-THBG (1.0 adduct/10(6) normal bases) were present in almost equal amounts in the mouse liver. Furthermore, there was an almost 5-fold excess of the two THBG diastereomers in the mouse liver DNA 6 days after exposure to BD when compared with rat liver DNA. The half-lives of (+/-)-THBG and meso-THBG appeared to be slightly longer in mouse liver (4.1 and 5.5 days, respectively) than in rat liver (3.6 and 4.0 days, respectively). The apparent persistence of these adducts in the mouse may contribute to the increased susceptibility of this species to BD-induced carcinogenesis. It is possible that (+/-)-THBG and meso-THBG could have also been derived from the reaction of DNA with the hydrolysis product of BDO2, 1,2-dihydroxy-3,4-epoxybutane (DHEB). Surprisingly, a vast majority of the studies in which the mutagenic and carcinogenic potential of BDO2 have been examined have only employed the commercially available (+/-)-BDO2. In light of the present findings, additional studies will be required to determine the potency of meso-BDO2 and the DHEB that is the precursor to meso-THBG as mutagens and carcinogens.     

Histamine immunoreactive neurons in the brain stem of the rabbit

Distribution of histamine-like immunoreactive (HA-LI) neurons in the rabbit brain stem was demonstrated by histamine antiserum. A number of HA-LI cell bodies were localized in the tuberomammillary nucleus of the posterior hypothalamus. A dense to moderate amount of HA-LI fibers was found distributed in the raphe nuclei, the inferior olive, the nucleus of the solitary tract, vestibular nuclei, and the paragigantocellular reticular nucleus in the medulla oblongata, and the parabrachial nuclei, the Klliker-Fuse nucleus, the pontine nuclei, and the locus coeruleus in the pons. HA-LI axons synapsed on dendrites of neurons in the nucleus of the solitary tract. This evidence suggests that histaminergic neurons control neuronal activity through synaptic transmission in the lower brain stem.