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G Rindi

Publications and source records attributed to G Rindi.

At least 145 records · Page 8Linked to original sources

Nervous tissue thiamine metabolism in vivo. I. Transport of thiamine and thiamine monophosphate from plasma to different brain regions of the rat.

The transport of thiamine (T) and thiamine monophosphate (TMP) across the blood-brain barrier was measured in vivo in the rat. Different doses of [14C]T (15-550 nmol) and [14C]TMP (11-110 nmol) were injected into the femoral vein. The content of T and its phosphoesters in blood and brain tissue (cerebellum, pons, medulla and cerebral cortex) 20 s after the injection was determined radiometrically after electrophoretic separation. Blood flow and blood volume in the same regions of the brain was also determined. Both T and TMP entered rapidly the cerebral tissue, where they were found chemically unmodified. The cerebral tissue extracted less than 7% of plasma T. At physiological plasma T concentrations, the rate of transport ranged from 0.43 to 0.65 nmol X g-1 X h-1 with only minor differences among the various regions. T was transported into the nervous tissue by two separate mechanisms: one saturable, that at physiological plasma T levels accounted for 95% (cerebellum) to 91% (cerebral cortex) of the total T taken up, and one non-saturable, that was most efficient in the cerebral cortex. The Km (half-saturation constant) of the former transport mechanism ranged from 1.95 to 2.75 nmol X ml-1 in the 4 areas investigated. Vmax (maximal transport rate) values ranged from 6 to 9 nmol X g-1 X h-1, the highest value being found in the cerebellum. The overall transport rate of TMP was on average 5-10 times as low as that of T and also showed a saturable and a non-saturable component. Both components were slower than those observed for T.

Animals↗

Nervous tissue thiamine metabolism in vivo. II. Thiamine and its phosphoesters dynamics in different brain regions and sciatic nerve of the rat.

Different steps of the metabolism of thiamine (T), thiamine mono- (TMP), pyro- (TPP) and triphosphate (TTP) in the cerebellum, brainstem, cerebral cortex and the sciatic nerve were evaluated in the rat in vivo. The radioactivity of T and its phosphoesters was determined at fixed time intervals (0.5-240 h) after an intraperitoneal injection of [14C]T (30 micrograms:1.25 muCi), under steady state conditions. The dynamics of thiamine compounds was evaluated using a compartmental mathematical model that allowed the fractional rate constants (FRC), turnover rates (TR) and turnover times to be calculated. The phosphorylation of T to TPP and the dephosphorylations of TPP to TMP and TMP to T could be estimated in all the structures investigated. Their turnover rates were found to be ordered in the sequence: cerebellum greater than brainstem greater than cerebral cortex greater than sciatic nerve. The transphosphorylation of TPP to TTP was so small that it could not be determined in a reliable way. Regional differences were found both the rate and in the composition of T and TMP mixture released from nervous structures. The shortest turnover time of TPP was found in the cerebellum, while the sciatic nerve exhibited the fastest renewal of T and TMP. In all the structures investigated TPP had a rather short turnover time, suggesting that its function might be associated to a rapid conversion into chemically different forms. The possible relationships between the rates of turnover of T compounds are the sensitivity of the nervous structures to T deficiency are discussed.

Animals↗

Ultrastructural localization of secretin in endocrine cells of the dog duodenum by the immunogold technique. Comparison with ultrastructurally characterized S cells of various mammals.

Secretin has been localized by the immunogold technique in endocrine cells of the dog duodenum--previously described as "K cells"--characterized by secretory granules with double structure consisting of a secretin-containing osmiophilic core surrounded by an argyrophil halo. Granules resembling those of dog secretin cells were also found in some ultrastructurally characterized S cells of the cat, pig, rat and rabbit duodenum, thus confirming in these species the identification of S cells with secretin cells. Conversely, the cells previously described as "S cells" in the dog lacked secretin immunoreactivity.

Animals↗

Thiamin absorption by small intestine.

In different animal species, including man, thiamin is absorbed in vivo from the small intestine by means of two mechanism: at low intraluminal concentrations (less than 1.5 microM), absorption shows a saturation kinetics; at higher concentrations, passive transport (diffusion) takes place. The absorption is maximal in the duodenum, its rate decreasing caudally along the small intestine. In vitro at low concentrations, the transcellular transport system of thiamin shows the following general features: it takes place against a chemical concentration gradient, is easily saturable (Km = 0.16-0.63 microM; Vmax = 5.2 mumol X g-1 X h-1), is blocked by cellular metabolic inhibitors, anoxia, low temperature and thiamin structural analogues. It is Na+-dependent and operates mainly from mucosa to serosa. In contrast, distinctive features of the thiamin transfer are the following: entry in the enterocyte in the free form (sodium-independent); pyrophosphorylation by means of a cytoplasm thiamin-pyrophosphokinase; the dephosphorylation of thiamin-pyrophosphate by means of particulate intracellular phosphatases; the cellular exit mainly in the free form, through the action of the controluminal Na-K activated ATPase. A working scheme for thiamin intestinal transport is proposed and discussed.

Animals↗

Sucralfate and carbenoxolone in the treatment of functional disturbances following partial gastrectomy.

30 patients submitted to partial gastrectomy (Billroth II) who later suffered digestive complaints (pain, "heartburn", bilious vomiting) showed gastric hyperemia, oedema and some erosions of the gastric stump when examined by endoscopy, the presence of cancer having been excluded by biopsy. These patients were randomly allocated into 2 groups of 15, one of which was treated with sucralfate (1 g 4 times), and the other with carbenoxolone (50 mg 4 times), daily for 8 weeks. After sucralfate the endoscopic finding showed a clear improvement in the gastric wall, accompanied by the almost complete disappearance of the complaint symptoms, in 13 cases (86.6%). After carbenoxolone the same improvement was observed at the endoscopy in 12 cases (80%), with similar recovery from symptoms. Nevertheless, no histological changes that could be attributed to the treatments were observed. In those patients whose endoscopic pattern remained unchanged by either drug, the complaints did not show any relief. No side-effects were detected during either of these drug treatments, each of which showed a similar therapeutic efficacy.

Aluminum↗

Ranitidine, cimetidine and antacids in the prevention of recurrence after healed duodenal ulcer: one-year experience.

A total of 110 subjects with duodenal ulcer healed with cimetidine (C) (50 patients), ranitidine (R) (40 patients) or pirenzepine (20 patients) was randomly divided in 3 groups. The first group (40 patients) was treated with R (150 mg nightly); the second group (40 patients) with C (400 mg nightly) and the third group with antacids as needed for symptomatic relief. The presence of the ulcer and its healing were established by endoscopy, which was repeated after 6 and 12 months of treatment, or previously if symptoms suggested recurrence. At the end of the year's follow-up, no recurrence of ulcers was observed in 75% of the R group, in 77.5% of the C group and in 40% of the antacids group. Some erosive duodenitis developed in the first and second groups (17.5% and 20% respectively), but none in the antacids group. Most of the ulcers that recurred did so in the first 6 months of treatment. No relevant side-effects were observed with the treatments described. Although no significant difference was detected between C and R treatments, both appeared to be clearly more effective than antacids. The usefulness of adequate prophylactic treatment against the tendency of duodenal ulcer to recur is stressed.

Antacids↗

Pirenzepine in long-term therapy for duodenal ulcer.

A total of 60 patients with endoscopically diagnosed duodenal ulcer were treated with pirenzepine or cimetidine for 8-10 weeks until endoscopic healing of the ulcer. After ulcer healing 20 random patients received 50 mg pirenzepine per os daily for 6 months, 20 received 400 mg cimetidine per os daily for 6 months, and the remaining 20 received topic antacids for 6 months whenever they complained of pyrosis and/or epigastric pain. Endoscopic checks were repeated after 6 months (or earlier, if clinical picture was consistent with relapsing ulcer). Relapsing duodenal ulcer or erosive duodenitis was observed in 5 patients treated with pirenzepine (25%), in 4 patients treated with cimetidine (20%), and in 13 patients treated with occasional antacids (65%). Differences were significant between the antacid-treated patients and each of the other two groups, but not significant between pirenzepine-treated and cimetidine-treated groups.

Adult↗

Intestinal glucose absorption in adrenalectomized rats: transport by isolated microvillous membrane vesicles.

D-glucose uptake by microvillous membrane vesicles, isolated from the intestine of the adrenalectomized, control (pair-fed) and normal rat, and incubated in 1 mM D-[U-14C]-glucose was measured. No qualitative difference in the time course of transport in the presence of an initial gradient of NaSCN or KSCN (100 mM, out greater than in) was found among the different groups. The small but significant decrease of 50% equilibration time (t 1/2) of adrenalectomized rat vesicles was aspecific, being the same as that of control, pair-fed (semistarved) animals. Thus adrenalectomy did not modify the transport properties of the rat luminal enterocyte membrane.

Adrenalectomy↗

Thiamin monophosphate in the CSF of patients with amyotrophic lateral sclerosis.

Free thiamin and thiamin monophosphate levels were determined by an electrophoretic fluorometric micromethod in plasma and CSF of patients with amyotrophic lateral sclerosis (ALS), alcoholics, and controls. In plasma of patients with ALS as well as in plasma and CSF of alcholics, both thiamin and thiamin monophosphate concentrations were decreased so that the thiamin-thiamin monophosphate (T/TMP) ratio remained unchanged compared with that of controls. In CSF of patients with ALS, however, thiamin monophosphate values decreased much more than thiamin levels, so that the T/TMP ratio was significantly increased. The selective impairment of thiamin monophosphate production by nerve cells is likely to result from the reduction of the activity of thiamin pyrophosphatase, an enzyme synthetized and highly concentratd in the Golgi complex. Thiamin pyrophosphatase is known to diminish in ALS as well as in experimental motor neuronal degeneration or axotomy. Thus, the T/TMP ratio could be taken as an index of the impairment of neuronal protein synthesis in ALS.

Adult↗

Localization of bombesin and GRP (gastrin releasing peptide) sequences in gut nerves or endocrine cells.

Five anti-gastrin releasing peptide (GRP) sera have been characterized against GRP, bombesin and related polypeptides spotted on cellulose acetate discs. Antibodies reacting with the C-terminal G-14 sequence of bombesin and the 19-27 sequence of GRP, were detected in all sera. Antibodies directed exclusively against the bombesin unrelated 1-17 sequence of GRP were found only in one serum (R-6902). With parallel immunohistochemical tests only the C-terminal immunoreactivity was detected in endocrine-paracrine cells of the chicken proventriculus, while both immunoreactivities were present in nerve fibres and a few nerve cell bodies of the mammalian gut. The distribution of GRP- and bombesin-like immunoreactive nerves in the gastric mucosa of both pyloric and oxyntic type the submucosal and myenteric plexus along the whole gastrointestinal wall and at sphincter regions is detailed.

Animals↗

Intestinal thiamin transport in rats. Thiamin and thiamin phosphoester content in the tissue and serosal fluid of everted jejunal sacs.

Rat everted jejunal sacs were incubated at 37 degrees C for 15-60 min in Krebs-Henseleit buffer, pH 7.4, with or without (control experiments) 0.2 microM [thiazole-2-14C]-thiamin. The determination of thiamin and its phosphoesters in the sac wall and in serosal fluid was carried out by an electrophoretic micromethod. Irrespective of the presence of 14C-thiamin, the tissue content of endogenous thiamin pyro- and triphosphate decreased during the incubation, whilst that of thiamin-monophosphate remained relatively constant. The tissue content of free thiamin increased substantially only in control experiments. Endogenous free thiamin, together with a small amount of monophosphate, was found to enter the serosal fluid. The transfer of both compounds was greatly enhanced by the incubation with 14C-thiamin, when an efficient thiamin phosphorylation could be demonstrated. During incubation with 14C-thiamin, the concentration of 14C-thiamin-pyrophosphate and, to a lesser extent, that of free 14C-thiamin increased progressively in the tissue, while 14C- thiamin-monophosphate content remained almost unchanged. No 14C-thiamin-triphosphate was detected. There was a rapid increase in the tissue specific radioactivity of free thiamin and thiamin-monophosphate, which preceded the rise in the specific radioactivity of thiamin-pyrophosphate. The specific radioactivities of the former compounds in the serosal fluid reflected those observed in the intestinal tissue. These results are interpreted as evidence suggesting that the active transport of thiamin is efficient only when intracellular thiamin phosphorylation is operating.

Animals↗

Metabolism of thiamin and its phosphoric esters in different regions of the nervous system: a new approach.

In the nervous system thiamin could have two main functions: coenzymatic, as thiamin pyrophosphate, and/or non-coenzymatic, but related to the nervous activity. In order to investigate the thiamin role we studied the turnover and metabolism of thiamin and its phosphoesters (mono-, pyro-, and tri-phosphate) in different regions (cerebellum, brain stem, cerebral cortex and sciatic nerve) of the nervous system, in a steady state condition. Practically, we determined the regional radioactivity of thiamin and its phosphoesters at different times (up to 240 hrs) from labeled thiamin administration, analyzing the obtained data by suitable compartmental models. From the results of two different types of experiment and from their mathematical elaboration, the cerebellum, with the highest thiamin compound content, appeared to be the most active region of the brain in different steps of thiamin metabolism (phosphorylation, dephosphorylation, uptake and release). The sciatic nerve, however, stood out for only thiamin and thiamin monophosphate metabolism, in spite of its very low total thiamin content.

Animals↗

Monophosphate, the only phosphoric ester of thiamin in the cerebro-spinal fluid.

With a specific and sensitive electrophoretic-fluorometric method, thiamin was found in the cerebro-spinal fluid of different mammals both in free and phosphorylated form, monophosphate being the only thiamin phosphoric ester. In humans, its amount was about 60% of total thiamin. Alcoholism greatly lowered total thiamin content, affecting both thiamin forms.

Alcoholism↗

Thiamin transport by rat small intestine "in vitro": influence of endogenous thiamin content of jejunal tissue.

The relationship between thiamin intestinal transport and phosphorylation in vitro was investigated using everted jejunal sacs from normal rats, rats affected with dietary thiamin deficiency at different degrees and relative pair-fed controls; recovered rats, i.e. severely thiamin-deficient animals, 6 hours after the intravenous injection of 1 mg of thiamin chloride/100 g body weight. The sacs were incubated at 37 degrees for 30 min with 0.2 microM 14C-labeled thiamin. During incubation, the endogenous phosphorylated thiamin undergoes a dephosphorylation, which is lowest in thiamin deficient rats. The jejunal sacs from all experimental groups take up and phosphorylate labeled thiamin: the rate is inversely proportional to the endogenous cellular content of phosphorylated thiamin. The net transport of labeled thiamin is enhanced in thiamin-deficient rats. The labeled thiamin net transport after incubation is linearly related to the labeled phosphorylated thiamin content of intestinal tissue. Thiamin repletion of severely thiamin-deficient rats restore the normal levels of endogenous free and phosphorylated thiamin in the intestinal within 6 hours. In addition after incubation, the labeled phosphorylated thiamin content reverts to the levels of the control, while thiamin net transport remains high.

Animals↗

A preliminary approach to the study of thiamine phosphorylation and dephosphorylation in some rat nervous regions and the liver.

Free and phosphorylated thiamine were determined in the liver and 9 regions of rat nervous system, after i.p. injection of labeled thiamine. A compartmental model was used to evaluate the rates of the phosphorylation of thiamine and the complete dephosphorylation of its phosphates. Remarkable differences between the liver and the nervous tissue as well as among different nervous regions were shown: high rates were found in hypothalamus, midbrain and cerebellum, low rates in cerebral cortex.

Animals↗

Thiamine content and turnover rates of some rat nervous regions, using labeled thiamine as a tracer.

The content of total thiamine radioactivity in some nervous structures and liver of the rat was determined in a steady state condition, using [thiazole-2-14C]thiamine as a tracer. The contents were analyzed by a mamillary type compartmental model which enabled us to calculate the influx and efflux fractional rate constants, turnover times, turnover rates and relative accuracy. Total thiamine turnover rates of the central nervous system regions were found to be ordered in the following sequence: cerebellum (0.55 microgram/g.h) greater than medullar and pons greater than spinal cord and hypothalamus greater than midbrain (plus thalamic area) and corpus striatum greater than cerebral cortex (0.16 microgram/g.h). Sciatic nerve turnover rate was 0.58 microgram/g.h. The turnover times were mainly between 5 and 10 h (range 2.4--16.4 h). The influx rate constants could be ordered as follows: cerebellum greater than hypothalamus, pons and medulla greater than corpus striatum, spinal cord, midbrain (plus thalamic area) and sciatic nerve greater than cerebral cortex. The results show in general a good agreement between turnover rate values and brain regional sensitivity to thiamine deficiency, the most vulnerable areas to thiamine depletion being those with the highest turnover rates.

Animals↗