Influence of repeated vitamin B administration on the frequency pattern analysed from rat brain electrical activity (tele-stereo-EEG)

Summary Recording of field potentials from different brain areas of freely behaving rats and subsequent spectral analysis of the signals has proved to be a most sensitive method in pharmacology. This new model is used to measure the effect on the electrical activity of the brain of repeated daily injections of 1 ml/kg of a vitamin B mixture (Neurobion^®, 1 ml containing 33.3 mg B₁, 33.3 mg B₆, and 0.333 mg B₁₂). Subacute application of the vitamin B combination for 1 week in a group of six rats resulted in changes in the power spectra, which became more prominent from day to day. Particularly increases in the power of the alpha₁ and beta range from the thalamus dominated the vitamin-induced changes. From the comparison with earlier results obtained with centrally acting serotonergic drugs, it is concluded that the pharmacodynamic action of the vitamin B mixture predominantly influences this transmitter system. The same group of animals, once challenged with a single dose of 0.2 mg/kg morphine before the repeated vitamin treatment, responded to the same challenge after the treatment in a more sensitive manner. Particularly power changes in the beta range were more pronounced. This higher sensitivity to a morphine challenge persisted for more than 1 week after the end of the vitamin treatment which points to a plastic change in serotonergic neurotransmitter control processes. The results obtained here may be linked to the antinociceptive properties of the vitamin B mixture and practical consequences may include a reduction of morphine dose for analgesia during repeated vitamin B treatment.     

Antioxidant protecting effects of vitamin B6 at reducing hemodynamic toxicity of gentamicin in rat model of nephrotoxicity

Routine therapeutic use of gentamicin in patients with preexisting renal failure may confront us with the toxic effects of aminoglycosides in the kidney known as nephrotoxicity. It is a common and often overlooked clinical entity that presents itself in the setting of oxidative stress-associated diseases in older individuals with renal failure. In this study, we investigated the antioxidant protecting effects of vitamin B₆ in the kidney, with a view on vasoregulatory role of renal pyridoxal 5′-phosphate at reducing the hemodynamic toxicity of gentamicin. Hence, 50 male Sprague–Dawley rats were randomly assigned in five groups to receive a corresponding dose of either normal saline, vitamin B₆ (100 mg/kg/bw; i.m.) or gentamicin alone (80 mg/kg/bw; i.m.), or in combination with vitamin B₆ at low (100 mg/kg/bw; i.m.) and high dose (200 mg/kg/bw; i.m.) for 10 days as animal model of nephrotoxicity. Daily administration of gentamicin at a dose of 80 mg/kg resulted in a significant increase in local and systemic oxidative stress and a decrease in glomerular functions as result of early hemodynamic toxicity. Histopathological examinations of renal tissues revealed acute tubular necrosis with hyaline cast formation triggered by gentamicin over 9 days of the experiment, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies in HVB group showed the protecting effects of supplemented vitamin B₆ at a high dose, including a slowdown in urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and ATPase activity up to 50 % when compared to low-dose rats and controls. In high-dose animals, normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that antioxidant properties of vitamin B₆ consistently increase with dose intensity. The present study also provided evidence that high dose of vitamin B₆ prevented both functional and histological renal changes induced by gentamicin in rats, more efficient than low dose of the vitamin.     

Differential involvement of central 5-HT<Subscript>1B</Subscript> and 5-HT<Subscript>3</Subscript> receptor subtypes in the antinociceptive effect of paracetamol

Objective: We investigated the effect of pre-treatment with ondansetron or CP 93129 (a 5-HAT_1B agonist) on the antinociceptive activity of paracetamol and the changes in central 5-HT₃ receptors induced by paracetamol alone or co-administered with ondansetron.Materials and Subjects: Male Wistar rats (eight per group) were injected with ondansetron (2 and 4 mg/kg s.c.) or CP 93129 (0.5, 1 and 2 mg/kg s.c.) 15 min before paracetamol (400 mg/kg, i.p.).Methods: Pain threshold was evaluated in the hot-plate or in the paw pressure test 30 min after the last treatment. 5-HT₃ receptor binding capacity was measured in the frontal cortex, temporal-parietal cortex and midbrain by means of radioligand binding technique. Statistical analysis was done using ANOVA followed by Student-Newman-Keuls test and 2 X 2 factorial analysis when appropriate.Results: Pre-treatment with ondansetron, at doses of 2 and 4 mg/kg, did not affect the antinociceptive activity of paracetamol in the hot-plate test and in the paw pressure test. Paracetamol did not change the characteristics of 5-HT₃ receptors in all the areas investigated. Ondansetron (4 mg/kg s.c) per se significantly increased the 5-HT₃ receptor number in the areas used, the effect not being modified by co-administration with paracetamol. On the other hand, CP 93129 (2 mg/kg s.c.) significantly prevented the effect of paracetamol in both algesimetric tests used.Conclusions: Our data indicate that 5-HT_1B but not 5-HT₃ receptors are involved in the antinociceptive effect of paracetamol in our experimental conditions.Received 25 November 2002; returned 10 April 2003; accepted by G. Geisslinger 22 April 2003     

Anatibant,a selective non-peptide bradykinin B2 receptor antagonist,reduces intracranial hypertension and histopathological damage after experimental traumatic brain injury

Bradykinin, the main metabolite of the kallikrein-kinin system and one of the first mediators released during inflammation, is well known to increase the permeability of the blood brain barrier (BBB) by activation of kinin B₂ receptors and hence promote brain edema formation following traumatic brain injury (TBI). Anatibant^® (LF 16-0687), a selective non-peptide bradykinin B₂ receptor antagonist, reduces brain edema after experimental TBI, however, so far no data are available if Anatibant^® reduces also the sequels of brain edema formation, i.e. morphological brain damage. Therefore, we investigated the effect of Anatibant (3.0 mg/kg b.w.) on intracranial pressure (ICP) and contusion volume after experimental TBI. Male C57/Bl6 mice (25–28 g) were subjected to Controlled Cortical Impact trauma (CCI). Anatibant^® was administrated as a subcutaneous bolus 15 min and 8 h after TBI. ICP was measured 3, 6, and 10 h after injury and contusion volume was quantified 24 h after trauma. Our data demonstrate a significant reduction of ICP (16.6 ± 1.67 mmHg vs. 24.40 ± 3.58 mmHg; n = 6; p = 0.002) and of contusion volume 24 h after trauma (28.28 ± 5.18 mm³ vs. 35.0 ± 3.32 mm³n = 7; p = 0.003) in treated mice. Therefore we conclude, that inhibition of bradykinin B₂ receptors seems to be a promising treatment option, and might therefore be investigated in clinical trails for the treatment of TBI.     

Vitamin B12-bindende Glykoproteine

Zusammenfassung 1. Mittels fraktionierter Ammonsulfatfällung bei pH 3,5 wurde sowohl aus einem Mischserum von Normalpersonen als auch aus einem Mischserum von Patienten mit chronischer myeloischer Leukämie (CML) jeweils ein Vitamin B₁₂-bindendes Protein isoliert. Nach säulenchromatographischer Reinigung mit DEAE-Sephadex^® A-50 ließ sich durch Dialyse eine spezifische Bindungskapazität (BBK) von 0,87 ng B₁₂/mg Protein für Normalserumprotein und von 4,54 ng für CML-Serumprotein ermitteln. Die Sedimentationskoeffizienten beider Serumglykoproteine betrugen 'S _{20 W} ^0.5 =3,0. Somit handelt es sich bei dem spezifisch B₁₂-bindenden Protein sicher nicht um TC I, sondern wahrscheinlich um TC II oder um ein anderes niedermolekulares Protein.2. Aus dem Harn von einer Normalperson und von drei CML-Patienten wurden durch sukzessive fraktionierte Fällung mit Ammoniumsulfat, 2% Rivanol^® und 0,067-M Glutaminsäure zusammen mit 2-M Ammoniumsulfat ziemlich reine Uroglykoproteine isoliert. Das Normaluroglykoprotein besaß eine BBK von 2,0 ng B₁₂/mg Protein, während die BBK-Werte bei den CML-Uroglykoproteinen zwischen 4,6 und 23,6 ng B₁₂/mg Protein betrugen.3. Zwischen spezifisch Vitamin B₁₂-bindenden Serum- und Uroglykoproteinen ließen sich imOuchterlony-Diffusionstest und bei der Autoradiographie keine immunologischen Unterschiede feststellen.Mit dankenswerter Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Vitamin B6 dose-dependently ameliorates renal hemodynamic toxicity of cisplatin in rat model of nephrotoxicity: the histopathologic and biochemical findings

Despite its significant anticancer activity, the clinical use of cisplatin is often limited by its undesirable side effects in the kidney known as nephrotoxicity. It is a common and often overlooked clinical entity that presents itself in the setting of oxidative stress-associated diseases in older individuals with renal failure. In this study, we investigated the antioxidant-protecting effects of vitamin B₆ in the kidney, with a view on the vasoregulatory role of renal pyridoxal 5′-phosphate at reducing the hemodynamic toxicity of cisplatin. Hence, 50 male Sprague–Dawley rats were randomly assigned in one of five groups of the study to receive a corresponding dose of either normal saline, vitamin B₆ (200 mg/kg/bw; i.m.) or cisplatin alone (7 mg/kg/bw; i.m.), or in combination with vitamin B₆ at low (100 mg/kg/bw; i.m.) and high dose (200 mg/kg/bw; i.m.) for 10 days as animal model of renal failure. Daily administration of cisplatin at a dose of 7 mg/kg/bw resulted in a significant increase in local and systemic oxidative stress of the kidney and a decrease in glomerular function as a result of early hemodynamic toxicity. Histopathological examinations of renal tissues revealed acute tubular necrosis with hyaline cast formation triggered by cisplatin over 9 days of the study, in addition to interstitial nephritis and tubular epithelial loss. Further biochemical studies in HVB group showed the protecting effects of supplemented vitamin B₆ at a high dose, including a slowdown in urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and ATPase activity up to 50 % when compared to the low-dose rats and controls. In high-dose animals, the normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that the antioxidant property of vitamin B₆ consistently increases with the dose intensity. The present study also provided evidence that high dose of vitamin B₆ prevented both functional and histological renal changes induced by cisplatin in rats, more efficient than low dose of the vitamin.     

Development of ic-ELISA and lateral-flow immunochromatographic strip for detection of vitamin B2 in an energy drink and vitamin tablets

Vitamin B₂ (riboflavin) is a water-soluble vitamin that has important roles in human health. In this study, we developed a sensitive and specific monoclonal antibody-based indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and lateral-flow immunochromatographic assay (ICA) strip for the rapid detection of vitamin B₂. Following routine fusion and selection, the optimum monoclonal antibody against vitamin B₂ was obtained. The 50% inhibitory concentration and limit of detection of ic-ELISA were 8.18 and 1.80?ng/mL, respectively. The cut-off value of the lateral-flow ICA strip was 50?ng/mL. The results revealed that our developed methods are suitable for the on-site detection and mass screening of vitamin B₂ in food and pharmaceutical products.     

Association of Vitamin B12 Deficiency and Metformin Use in Patients with Type 2 Diabetes

We evaluated the prevalence of vitamin B₁₂ deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B₁₂ and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B₁₂ deficiency was defined as vitamin B₁₂ ≤ 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B₁₂ deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B₁₂ level was 662.5 ± 246.7 pg/mL. Vitamin B₁₂ deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of ≤ 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and ≥ 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and ≥ 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B₁₂ deficiency, especially at higher dosages (> 1,000 mg) and longer durations (≥ 4 yr) of treatment.

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The effect of glutathione,vitamins B12 and B1. and rutin on the level of cholesterol in the brain,liver and blood in alimentary hypercholesterinemia

Summary The paper deals with materials on the effect of glutathione, vitamins B₁₂ and B₁, rutin and a combination of glutathione with vitamin B₁ or rutin on the cholesterol level in the blood, liver and brain during alimentary hypercholesterinemia. Experiments were staged on 266 chicks.Hypercholesterinemia was provoked by cholesterol-containing diet given for a period of 18 days. After the cessation of cholesterol administration, the chicks were given vitamin B₁₂ in a dose of 0.1 and 2, 0.2 mg of vitamin B₁ subcutaneously, rutin with food –100 mg per kg of body weight, glutathione –12.5 mg per 100 g of weight and combinations of glutathione with rutin or with vitamin B₁ in the aforesaid doses for a period of 10, 15, and 20 days. The chicks were decapitated after suspension of this treatment. Cholesterol concentration was determined in the blood, liver and brain. As established, cholesterol feeding markedly increased its content in the blood and liver. After discontinuance of cholesterol administration its content in the blood and liver drops almost to the initial level in 20 days. The hypocholesterizing effect of vitamin B₁₂ given in a dose of 0.1, of glutathione-rutin combination and of rutin alone was established. These were no changes in the cholesterol content of the brain tissue.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten Ékjsperimental'noi Biologii i Meditsiny, Vol. 51, No. 2, pp. 46–48, February, 1961     

Effect of acute and repeated administration of paracetamol on opioidergic and serotonergic systems in rats

Objective and design: We investigated the antinociceptive effect of paracetamol or morphine after repeated administration and the changes in the characteristics of central μ-, κ- and 5-HT₂ receptors. Treatment: Male rats were injected twice a day for seven days with paracetamol (400 mg/kg, i. p.) or morphine (5 mg/kg, s. c.). Methods: The antinociceptive effect was evaluated 30 min after single and multiple doses of paracetamol and morphine through the hot-plate test. Binding techniques were used to evaluate the receptor characteristics in the frontal cortex. Results: Both paracetamol and morphine induced an antinociceptive effect on day 1 but only paracetamol maintained this effect for seven days while morphine did not. The number of μ-opioid receptors decreased on days 1, 3, and 7 by a similar percentage after paracetamol administration (by 29, 31 and 34 %, respectively), while morphine produced a progressive decrease in comparison with controls (by 37, 49 and 60 %, respectively) and κ-opioid receptors were unaffected. Both drugs similarly decreased the 5-HT₂ receptor number on all days of treatment (by about 30 %). Conclusions: The opioidergic and serotonergic systems are involved in different ways in the induction and maintenance of antinociception after paracetamol or morphine treatment. Received 10 May 2006; returned for revision 14 September 2006; accepted by G. Geisslinger 30 October 2006     

The effects of vitamin E on penicillin-induced epileptiform activity in rats

Epilepsy is a disorder characterized by recurrent seizures, which can increase the content of reactive oxygen in the brain. Active oxygen free radical scavengers such as ascorbic acid or α-tocopherol (vitamin E) might prevent epilepsy. A variety of animal seizure models exist which help to document the effects of vitamin E and specify its action. In this study, we have evaluated dose-dependent effect of α-tocopherol on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, 100, 300, or 500 mg/kg of α-tocopherol was administrated intramuscularly (i.m.). α-Tocopherol (100, 300, or 500 mg/kg) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. α-Tocopherol of 300, or 500 mg/kg significantly decreased the frequency of epileptiform activity in the penicillin-pretreated animals. The low dose of α-tocopherol (100 mg/kg) did not significantly change either amplitude or frequency of epileptiform activity. α-Tocopherol of 500 mg/kg i.m. was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The anti-convulsant effects of α-tocopherol appeared 80, 60, 30 min after α-tocopherol injection in 300, 500, and 3 day vitamin E supplemented groups. These data indicate that α-tocopherol decreases the frequency of penicillin-induced epileptic activity.     

Immunohistochemical distribution of vitamin B12 R-binder in renal cell carcinoma

Summary Renal cell carcinomas and normal kidney tissues were examined for the expression of vitamin B₁₂ R-binder by the indirect immunoperoxidase method. In normal kidney tissue, the presence of the vitamin B₁₂ R-binder was shown to be confined to the straight portion (pars recta) of proximal tubules. Seven of the 38 cases of renal cell carcinoma (18%) expressed the vitamin B₁₂ R-binder antigen. This provides a further evidence of the proximal tubular nature of renal cell carcinoma, and suggests that a small proportion of renal cell carcinomas originate from the straight portion of the renal proximal tubules.     

Instantaneous measurement of glomerular filtration rate in the isolated perfused rat kidney

In perfusion studies on the isolated cellfree perfused rat kidney, the glomerular filtration rate (GFR) can be controlled if the GFR can be measured instantaneously. This paper reports on a GFR meter which opens this possibility. Vitamin B₁₂ is used as a marker for the GFR. A bubble flow meter determines urine flow rates ranging from 10 up to 200 l · min^–1. A fiberoptic colorimeter measures vitamin B₁₂ concentrations in the urine up to 400 mg · l^–1. The flow meter and the colorimeter are described in detail. The reliability of vitamin B₁₂ as a marker for the GFR is demonstrated and, moreover, the identity of GFR values obtained with the GFR meter and those from B₁₂ spectrophotometry is demonstrated.     

Changes in activity of some mechanisms of specific and nonspecific immunity in vitamin B1 deficiency

The effect of thiamine deficiency on the immune response and activity of certain mechanisms of natural immunity was studied in adult rats. Thiamine deficiency was simulated experimentally by a single injection of hydroxythiamine, a vitamin B₁ antagonist. Administration of hydroxythiamine caused a marked decrease in complement activity, phagocytic activity of the peripheral blood leukocytes, bactericidal activity of the serum, and antibody production in response to immunization with sheep's red blood cells. Conversely, lysozyme activity increased. In vitamin B₁ deficiency the intensity of incorporation of [¹⁴C]leucine into liver protein synthesis was reduced.Department of Pathological Physiology, N. I. Sechenov First Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR G. V. Vygodchikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 60–62, July, 1979.     

Inhibition of the action of tetanus toxin by vitamin B1

Experiments on rabbits showed that preliminary injections of vitamin B₁ and their continuation after injection of tetanus toxin increased the resistance of the animals to tetanus. A more marked protective effect was observed if the tetanus toxin was injected into the rabbits in vitamin B₁ solution. Injection of the vitamin 2 h after the toxin led to a tendency toward an increase in resistance.     

Systemic immunosuppression following a single pharyngeal aspiration of 1,2:5,6-dibenzanthracene in female B6C3F1 mice

1,2:5,6-Dibenzanthracene (DBA) is ubiquitous in our environment as a contaminant produced by incomplete combustion of organics from sources such as forest fires, cigarette smoke, and asphalt paving, and it is more immunosuppressive of the T-dependent antibody-forming cell (AFC) response than the well-studied polycyclic aromatic hydrocarbon, benzo(a)pyrene. The systemic immunosuppressive effects of DBA were investigated following a single pharyngeal aspiration (pa) in female B₆C₃F₁ mice. The immunotoxic effects of DBA were evaluated using numerous assays of varying complexity to evaluate innate (natural killer [NK] cell activity), cell-mediated (T-lymphocyte proliferation, mixed leukocyte response [MLR], cytotoxic T-lymphocyte [CTL] activity, delayed-type hypersensitivity [DTH]), and humoral immunity (B-lymphocyte proliferation, T-dependent antibody responses). A single pa of DBA at doses up to 30?mg/kg had no effect on NK cell activity, anti-CD3 antibody-mediated T-lymphocyte proliferation, the MLR, or B-lymphocyte proliferation. DBA at 30?mg/kg suppressed Concanavalin A (ConA)-stimulated T-lymphocyte proliferation and the CTL response. DBA exposure reduced cytokine production in spleen cell culture supernatants after in vitro stimulation with ConA or lipopolysaccharide (LPS). Immunosuppression was observed at lower doses in the holistic assays. The DTH response to Candida albicans was significantly decreased at 3.0?mg/?kg DBA, while the AFC response was intermittently suppressed at 1.0?mg/kg, with no effect observed at 0.3?mg/kg. These results demonstrate that a single pa of DBA produces systemic immunotoxicity, and of the assays utilized, the holistic assays (i.e., DTH, AFC) appear to be most sensitive to the immunosuppressive effects of DBA.     

Seminiferous epithelium damage after short period of busulphan treatment in adult rats and vitamin B12 efficacy in the recovery of spermatogonial germ cells

Several different strategies have been adopted in attempt to recover from chemotherapy‐damaged spermatogenesis that is often seen in oncologic patients. In this study, we have evaluated the impact of short period of exposure to busulphan on the haemogram and seminiferous epithelium of adult rats, focusing on spermatogonial depletion and Sertoli cell (SC) integrity. We then examined whether vitamin B₁₂ supplementation improves the haematological parameters and spermatogonia number. The animals received 10 mg/kg of busulphan (BuG) or busulfan+vitamin B₁₂ (Bu/B₁₂G) on the first and fourth days of treatment. In H.E.‐stained testicular sections, the areas of the seminiferous tubule (ST) and seminiferous epithelium were measured. The number of spermatogonia in H.E‐stained and PCNA‐immunolabelled testicular sections was quantified. The frequency of tubules with abnormal SC nuclei or TUNEL‐positive SC was evaluated. Vimentin immunofluorescence in ST was also evaluated. In BuG and Bu/B₁₂G, the animals showed leukopenia and thrombocytopenia, but the body weight reduced only in BuG. The areas of ST and seminiferous epithelium decreased in Bu/B₁₂G and BuG. In BuG, the number of H.E.‐stained and PCNA‐immunolabelled spermatogonia reduced significantly. The frequency of tubules containing abnormal SC nuclei and TUNEL‐positive SC increased and the vimentin immunoexpression pattern changed. In Bu/B₁₂G, the number of H.E.‐stained or PCNA‐immunolabelled spermatogonia increased fourfold in comparison with BuG. The structural changes in ST after 6 days of busulphan exposure may be associated with the potential effect of this anti‐neoplastic agent on SC. The increased number of spermatogonia in the busulphan‐treated animals receiving vitamin B₁₂ indicates that this vitamin can be an adjuvant therapy to improve the fertility in male cancer patients.     

Phosphate fluxes in isolated enterocytes from vitamin D replete and vitamin D deficient rats — early effects of calcitriol

In the present work we studied rapid in vitro effects of calcitriol (1,25(OH)₂ vitamin D₃) on the intestinal transport of inorganic phosphate (P_i). Enterocytes from vitamin D replete (D⁺) as well as vitamin D depleted (D^–) rats were isolated mechanically from the duodeno-jejunum. In this model, P_i uptake was a temperature and Na⁺-dependent phenomenon. The in vitro-addition of calcitriol (1 pM) resulted in a significant enhancement of initial P_i uptake rate by enterocytes from D⁺ (P<0.01) and D^– (P<0.05) rats. This effect which was Na⁺-dependent, was observed within the time of 20 min, but not before. A similar effect on P_i uptake rates of D⁺ or D^– enterocytes could be elicited by the in vitro addition of the methyl ester of cis-vaccinic acid (MCVA) which is thought to increase membrane fluidity by modifying the lipid composition of the cell membrane. The stimulatory effect of calcitriol on P_i uptake rate was blunted in the presence of the methyl ester of transvaccinic acid (MTVA) thought to decrease membrane fluidity. Enterocyte P_i efflux rate constant (^o KP_i) remained unchanged in the presence of calcitriol (1 pM). In conclusion, the study demonstrates a rapid in vitro effect of calcitriol on P_i uptake by isolated enterocytes from D⁺ and D^– rats. It suggests, but does not prove, that the hormone may act via an action independent of genomic nuclear activation.     

Increases of kinin B1 and B2 receptors binding sites after brain infusion of amyloid-beta 1-40 peptide in rats

Although numerous inflammation pathways have been implicated in Alzheimer's disease, the involvement of the kallikrein–kinin system is still under investigation. We anatomically localized and quantified the density of kinin B₁ and B₂ receptors binding sites in the rat brain after the infusion of amyloid-β (Aβ) peptide in the right lateral brain ventricle for 5 weeks. The conditioned avoidance test showed a significant reduction of memory consolidation in rats infused with Aβ (68.6 ± 20.9%, P < 0.05) when compared to control group (90.8 ± 4.1%; infused with vehicle). Autoradiographic studies performed in brain samples of both groups using [¹²⁵I]HPP-[des-Arg¹⁰]-Hoe-140 (150 pM, 90 min, 25 °C) showed a significant increase in density of B₁ receptor binding sites in the ventral hippocampal commissure (1.23 ± 0.07 fmol/mg), fimbria (1.31 ± 0.05 fmol/mg), CA1 and CA3 hippocampal areas (1.05 ± 0.03 and 1.24 ± 0.02 fmol/mg, respectively), habenular nuclei (1.30 ± 0.04 fmol/mg), optical tract (1.30 ± 0.05 fmol/mg) and internal capsule (1.26 ± 0.05 fmol/mg) in Aβ group. For B₂ receptors ([¹²⁵I]HPP-Hoe-140, 200 pM, 90 min, 25 °C), a significant increase in density of binding sites was observed in optical tract (2.04 ± 0.08 fmol/mg), basal nucleus of Meynert (1.84 ± 0.18 fmol/mg), lateral septal nucleus – dorsal and intermediary portions (1.66 ± 0.29 fmol/mg), internal capsule (1.74 ± 0.19 fmol/mg) and habenular nuclei (1.68 ± 0.11 fmol/mg). In control group, none of these nuclei showed [¹²⁵I]HPP-Hoe-140 labeling. This significant increase in densities of kinin B₁ and B₂ receptors in animals submitted to Aβ infusion was observed mainly in brain regions related to cognitive behavior, suggesting the involvement of the kallikrein–kinin system in Alzheimer's disease in vivo.     

The urinary excretion of assayable vitamin B12 and radioactivity after parenteral 58Co B12 in man

Evidence is presented that after injection of radioactive vitamin B₁₂ in man, there is a close correlation between the amount of radioactivity excreted and the amount of assayable vitamin B₁₂ excreted, and thus that the amount of radioactivity excreted is a true measure of the vitamin B₁₂ excreted. The possible reasons for this occurrence are discussed and it is suggested that in the body vitamin B₁₂ does not exist as such but as an analogue or active derivative.