Action Of Mannitol Research Articles

Comments: New approach to treat an old problem: Mannitol for post dural puncture headache.

Sir, We read with great interest the article, ‘New approach to treat an old problem: Mannitol for post-dural puncture headache (PDPH)’.[1] PDPH is a low pressure headache. The role of cerebrospinal fluid (CSF) leak and lowering CSF pressure are the causes for the headache. Two theories are postulated in this regard.[2,3] First, decrease in CSF pressure leading to the traction on the pain sensitive parietal dura and intracranial structures leading to the headache. The second theory is based on the Monro Kellie doctrine[2] which states that the sum of volume of brain, CSF and intracranial blood is kept constant; loss of CSF leads to increase in the blood volume due to venodilatation. This venodilatation is attributed as the cause of the headache. As rightly mentioned in the article, there is no evidence suggesting a role for use of mannitol in relieving PDPH which is a low pressure headache. Mannitol is a drug commonly used for lowering high intracranial pressure (ICP). The mechanism leading to reduction in PDPH may be explained as below: ICP reduction can be due to two mechanisms, the early reduction being due to plasma expansion and late, due to diuresis.[4] Plasma expansion reduces the blood viscosity and increases the cerebral blood flow and oxygenation. This eventually leads to a probable reduction in the headache due to cerebral vasoconstriction as a compensatory mechanism. This may be cited as the reason behind the improvement of the headache. As far as the osmotic action of mannitol is concerned, an intact blood brain barrier is a prerequisite, and frequent dosing would cause dyselectrolytaemia and dehydration which would worsen the situation.[4] Another theory can be related to the rebound increase in ICP that can occur after the initial reduction because of the eventual passage of mannitol into the brain. This rebound phenomenon[4,5] is particularly associated with mannitol administration in a patient without an intact blood brain barrier which is possibly the case here. But utilising this disadvantage of mannitol to get relief from a self-limiting headache which is expected to resolve in 50% of the patients in 3–4 days[2] and as well as subjecting them to the risk of dehydration and electrolyte imbalance may not be acceptable.

Comparison of DNA Damage Photoinduced by Ketoprofen, Fenofibric Acid and Benzophenone via Electron and Energy Transfer¶

Ketoprofen (KP) and fenofibrate, respectively, anti-inflammatory and hypolipidemiant agents, promote anormal photosensitivity in patients and may induce photoallergic cross-reactions correlated to their benzophenone-like structure. Here, their ability to photosensitize the degradation of biological targets was particularly investigated in DNA. The photosensitization of DNA damage by KP and fenofibric acid (FB), the main metabolite of fenofibrate, and their parent compound, benzophenone (BZ), was examined on a 32P–end-labeled synthetic oligonucleotide in phosphate-buffered solution using gel sequencing experiments. Upon irradiation at λ > 320 nm, piperidine-sensitive lesions were induced in single-stranded oligonucleotides by KP, FB and BZ at all G sites to the same extent. This pattern of damage, enhanced in D2O is characteristic of a Type-II mechanism. Spin trapping experiments using 2,2,6,6-tetramethyl-4-piperidone have confirmed the production of singlet oxygen during drug photolysis. On double-stranded oligonucleotides, highly specific DNA break occurred selectively at 5′-G of a 5′-GG-3′ sequence, after alkali treatment. Prolonged irradiation led to the degradation of all G residues, with efficiency decreasing in the order 5′-GG > 5′-GA > 5′-GC > 5′-GT, in good agreement with the calculated lowest ionization potentials of stacked nucleobase models supporting the assumption of a Type-I mechanism involving electron transfer, also observed to a lesser extent with adenine. Cytosine sites were also affected but the action of mannitol which selectively inhibited cytosine lesions suggests, in this case, the involvement of hydroxyl radical, also detected by electronic paramagnetic resonance using 5,5-dimethyl-1-pyrrolidine-1-oxide as spin trap. On a double-stranded 32P–end-labeled 25-mer oligonucleotide containing TT and TTT sequences, the three compounds were found to photosensitize by triplet–triplet energy transfer the formation of cyclobutane thymine dimers detected using T4 endonuclease V.

Mannitol in reperfusion skin island flaps injury

In the skin, the concept of reperfusion injury is well established. The application of this knowledge to deal with skin flap surgery problems, has a great prophylactic potential. This experimental study was performed to evaluate the action of mannitol as a scavenger of oxygen-free radicals, after an ischemia-reperfusion injury on skin island flaps. Thirty six male Wistar rats were divided into three test groups (n = 12): a non-ischemic group (group I), and two others (groups II and III) which were subjected to nine hours of ischemia following by 30 minutes of reperfusion. After seven days, all animals of group II, treated with saline, showed full skin flap necrosis. The assessment of group III, that received a 20% solution of mannitol prior to the onset of reperfusion, revealed 75% (9/12) of flap viability. These results suggest that pre-treatment with mannitol is able to enhance flaps survival with significantly less tissue necrosis (p <0.02).

Action of mannitol in ciguatoxin-intoxicated rats

This study reports the effects of mannitol on nerve conduction when used as a therapeutic agent in mammals following the administration of ciguatoxin. Electrophysiological studies were performed in vivo on the rat ventral coccygeal nerve. The absolute and relative refractory periods, conduction velocity and the supernormal response were measured in rats treated with i.p. ciguatoxin, both prior to, and following, the infusion of i.v. mannitol. Ciguatoxin induced significant prolongation of the absolute refractory period as well as significant slowing of the compound nerve conduction velocity. The magnitude of the supernormal response was significantly increased and the duration of the supernormal period extended in ciguatoxin-treated animals. Recordings collected following the infusion of mannitol in these ciguatoxin-treated animals showed that mannitol did not reverse the effects of ciguatoxin on nerve conduction in any of the parameters measured.

Stimulation of ACC oxidase activity « in vivo» by different effectors is differentially sensitive to inhibitors

Summary The 1-aminocyclopropane-l-carboxylate oxidase (ACC-ox) reaction of cultured sycamore cells was previously shown to be stimulated « in vivo » by fusicoccin and plasma-membrane (PM) red-ox activity. In this paper we report that a stimulation of « in vivo » ACC-ox was also obtained by administration of isobutyric acid (IBA) and staurosporine to the cultures. A comparison of the characteristics of the stimulation by all of these different chemicals has shown that: 1) as with fusicoccin-induced, the red-ox-induced ethylene formation was inhibited by high osmotica (0.6 mol/L mannitol); 2) on the contrary, the stimulation of ethylene production, either by IBA or by staurosporine, was insensitive to plasmolyzing mannitol; 3) ethylene overproduction, sensitive to mannitol, was also inhibited by vanadate, an inhibitor of the PM proton pump, and by tetraethylammonium (TEA), an inhibitor of PM K + channels; and 4) any stimulation insensitive to plasmolyzing mannitol was not inhibited either by vanadate or by TEA. The relationship between the action of mannitol and the ACC-ox activity was also investigated. A gende rehydration of the mannitol-treated cells led to the recovery of a large part of the stimulation, while this did not occur if the cells were subjected to a rapid rehydration in the cold which leads to an osmotic shock. The data indicate that two differently regulated types of ethylene production are present in sycamore cells and that one of these is largely dependent on the biochemical and physical status of the cell membranes.

Mechanism of Action of C2H4 in Promoting the Germination of Cocklebur Seeds. III. A Further Enhancement of Priming Effect With Nitrogenous Compounds and C2H4 Responsiveness of Seeds

Efficiency of organic or inorganic osmotica for seed priming of cocklebur (Xanthium pennsylvanicum Wallr.) revealed that KNO3 was the most promising, and was more effective than mannitol or other salts at the same concentration (200 mM) and was independent of the C2H4 action. However, KNO3 applied as a priming reagent enhanced the effect of C2H4 or that of the water stress imposed with mannitol. Unlike the action of mannitol, both KNO3M and C2H4 augmented the pool size of amino acids in seed cells. However, below 50 mM KNO3 imposing no stress only slightly, though insignificantly, affected the germinability as well as the levels of total cyanogen. On the other hand, at a high concentration which imposed water stress on the seeds, 200 mM KNO3 remarkably elevated the contents of both cyanogenic glycosides and lipids in the excised cotyledons. When C2H4 was added with KNO3, the level of cyanogenic compounds significantly increased but when added without KNO3, the contrary effect was shown. Hence the enhancement of the mannitol-induced priming effect by nitrogenous reagents in cocklebur seeds could be implicated in the accumulation of cyanogenic compounds. Unlike cocklebur, both common chickweed and barnyard grass seeds are very responsive to 30 mM KNO3 on germination, and such species abundantly contain cyanogen. The amount of cyanogen was further augmented by contact with KNO3 at only 30 mM. The role of NO-3 -dependent cyanogenesis is highlighted in relation to germination response of seeds.

Pronounced increases in brain levels of calcitonin gene-related peptide after kainic acid induced seizures

Changes in immunoreactivity of calcitonin gene-related peptide (CGRP) were investigated in the brains of rats subsequently to seizures induced by intraperitoneal injection of kainic acid (10 mg/kg, i.p.). Increased levels of the neuropeptide were observed in the frontal cortex (increase of 1300% of control value), striatum (900%), dorsal hippocampus (400%) and amygdala/pyriform cortex (135%) three days after injection of the neurotoxin. Intravenous infusion of mannitol (1.5 g/kg, under thiopental anesthesia) which prevents seizures and post-seizure brain damage suppressed the changes in CGRP-like immunoreactivity. Injection of pentylenetetrazol causing generalized motor seizures resulted in no change of CGRP-immunoreactivity after three days. The pronounced but reversible increases of brain CGRP levels suggest a strong but short-lasting activation of the peptide system. The failure of pentylenetetrazol to produce a similar effect and the protective action of mannitol suggest that sustained seizures and/or post-seizure brain damage may be required to produce the rise in peptide levels.

The Na+/H+ exchange system in glial cell lines. Properties and activation by an hyperosmotic shock.

The properties of the Na+/H+ exchange system in the glial cell lines C6 and NN were studied from 22Na+ uptake experiments and measurements of the internal pH (pHi) using intracellularly trapped biscarboxyethyl-carboxyfluorescein. In both cell types, the Na+/H+ exchanger is the major mechanism by which cells recover their pHi after an intracellular acidification. The exchanger is inhibited by amiloride and its derivatives. The pharmacological profile (ethylisopropylamiloride greater than amiloride greater than benzamil) is identical for the two cell lines. Both Na+ and Li+ can be exchanged for H+. Increasing the external pH increases the activity of the exchanger in the two cell lines. In NN cells the external pH dependence of the exchanger is independent of the pHi. In contrast, in C6 cells, changing the pHi value from 7.0 to 6.5 produces a pH shift of 0.6 pH units in the external pH dependence of the exchanger in the acidic range. Decreasing pHi activates the Na+/H+ exchanger in both cell lines. Increasing the osmolarity of the external medium with mannitol produces an activation of the exchanger in C6 cells, which leads to a cell alkalinization. Mannitol action on 22Na+ uptake and the pHi were not observed in the presence of amiloride derivatives. Mannitol produces a modification of the properties of interaction of the antiport with both internal and external H+. It shifts the pHi dependence of the system to the alkaline range and the external pH (pHo) dependence to the acidic range. It also suppresses the interdependence of pHi and pHo controls of the exchanger's activity. NN cells that possess an Na+/H+ exchange system with different properties do not respond to mannitol by an increased activity of the Na+/H+ exchanger. The action of mannitol on C6 cells is unlikely to be mediated by an activation of protein kinase C.

Ultrastructural changes in the myxamoebae of Physarum polycephalum in response to a microcyst-inducing concentration of mannitol

The response of axenically cultured Physarum polycephalum myxamoebae to a microcyst-inducing concentration of mannitol (0.5 M) has been studied for both log-phase and maximum-concentration cultures. Results indicate that mannitol alone is not sufficient to induce encystment; a population effect is also necessary. Myxamoebae may continue to divide in the presence of mannitol if this effect is absent. Early ultrastructural changes have been noted indicating that the primary mode of action of mannitol is via the change in osmotic potential of the medium. Nuclear and cytoplasmic ultrastructural changes during the encystment process are documented. Recovery of log-phase cells to undergo mitosis involves definite morphological changes, which are also described. Ruthenium red staining was utilised to emphasize changes in the cell coat and indicate possible sites of accumulation of cell wall material.

Effect of mannitol and furosemide on urinary fluoride excretion of surgical patients anaesthetized with enflurane or halothane.

Urinary excretion of fluoride after enflurane anaesthesia has been found to correlate with urinary pH, while the correlation with urinary volume has remained unsettled. We therefore studied the effect of moderate doses of mannitol and furosemide on serum fluoride levels and urinary excretion of fluoride in surgical patients after controlled doses of enflurane (6+6+6 patients) or halothane (5+5+5 patients). The highest serum fluoride level was 31 mumol/1 in an enflurane patient (enflurane dose 1.26 end-tidal vol % x h) and 8 mumol/1 in a halothane patient (halothane dose 0.59 end-tidal vol. % x h). Mannitol caused th greatest mean excretion of fluoride (not significant (n.s)) in the enflurane patients without any marked rise in urinary pH or volume. Furosemide increased urinary output markedly but did not enhance urinary fluoride excretion or raise urinary pH. Compared with the control groups of both inhalation anaesthetic patients, the diuretics appeared to have no effect on the serum fluoride levels. In the enflurane patients there was a positive correlation between the change in fluoride clearance and the change in urinary pH, but no with the change in urinary volume during the first postoperative hours. On the other hand, in the halothane patients there was a positive correlation between the change in fluoride clearance and the change in urinary volume. A possible "fluoro-uretic" action of mannitol was also seen in the halothane patients, as in the later postoperative period fluoride excretion was greatest when mannitol had been given.

The renal response to ureteral obstruction: a model for the study of factors which influence glomerular filtration pressure.

Abstract The relationship of glomerular filtration pressure to filtration rate has been examined under various experimental conditions in the rat. Unilateral ureteral obstruction, of 24 hours' duration, produces a marked reduction in filtration rate, measured after release of occlusion. This excretory lesion is associated with a reduction in glomerular filtration pressure. The relationship between filtration rate and pressure after release of obstruction closely resembles that observed in the normal kidney in which perfusion pressure is reduced by aortic constriction. The data indicate that the reduction in filtration pressure is the sole factor responsible for excretory failure after ureteral obstruction and that this lesion is characterized by an increase in preglomerular arteriolar resistance. This conclusion is supported by the observation that the intraarterial infusion of vasodilators, papaverine and acetylcholine, markedly augments filtration rate and pressure in the affected kidney. The effect of volume expansion with mannitol or albumin solutions has been studied in this lesion. Both produce a rapid and marked increase in filtration rate and pressure after release of obstruction. The effect of mannitol on filtration pressure appears to be manifest only in the free flow state, not when mannitol is given after ureteral clamping. This suggests that the action of mannitol is mediated by an intrarenal feedback mechanism responsive to changes in sodium delivery to the distal nephron. Although the precise mechanism involved in the pathogenesis of decreased filtration pressure after unilateral ureteral obstruction remains undefined, this appears to offer a simple and useful model for the study of physiologic and pathologic factors which affect glomerular filtration pressure.

Prevention of acute anuria with special regard to the administration of mannitol.

Authors give a brief review of the pathogencsis of acute anuria and record therapeutic methods as hibernation, hypothermia, i. v. novocaine, osmotic diuretic, paravertebral novocaine blockade, avoiding anuria when administering in due time. Action of mannitol is delt with in details. Favourable clinical results show high value of mannitol in preventing anuria.