Montelukast influence on kidney in experimental induced diabetes mellitus.

Leukotrienes are important icosanoids group involved in a lot of normal and pathological states. Montelukast (MK) is a selective cysteinyl leukotriene receptor (Cys LT1) antagonist. Purpose. The purpose of the study is to observe the influence of MK on renal damage caused by experimental diabetes in rats. The experiment was carried out on four groups of adult male Wistar rats. Lot I was a witness and received 1.5ml of physiological saline ip. in unique dose on the first day of the experiment. Lots II and III have been caused experimental diabetes by streptozotocin (STZ) administration of 60mg/kg ip. in the unique dose. Lot III also received MK daily 10mg/kg/day daily 8weeks.Lot IV received only MK 10mg/kg/day daily 8 weeks. After eight weeks all animals were anesthetized and were sacrificed. The following pathological modifications were observed: tubular injury, glomerular hypertrophy and lesions, leukocytes infiltration. Obtained data showed that MK has significantly reduced the intensity of glomerular lesions (score 3.50+/-0.21 in STZ lot vs. 2.50+/-0.17 in STZ+MK lot p<0.01) and tubular damages. Renal interstitial leukocyte infiltration in animals with diabetes has been also reduced by MK. MK has a partially protective action against the lesions produced by experimental diabetes.

The diagnostic utility of the "Thwaites' system" and "lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients.

BACKGROUND: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. METHODS: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. RESULTS: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. CONCLUSION: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

Protective effect of magnesium and metformin on endometrium and ovary in experimental diabetes mellitus.

We evaluated the effect of magnesium and metformin on streptozotocin (STZ)-induced diabetes mellitus (DM) in non-pregnant female rats. The study comprised four groups, each consisting of eight, non-pregnant, adult Wistar female rats with a weight range of 170-250 g, maintained under the usual laboratory conditions. One group of female rats was the control group that received no treatment. To induce DM, the other three groups of animals received streptozotocin (STZ), 60 mg/kg i.p. (in a single dose). The first STZ group received no additional treatment. The second group received MgCl2 1 mmol/kg/day i.p. daily, for eight weeks. The third group received daily metformin, 100 mg/kg/day per os (endogastric probe), for eight weeks. Blood glucose, total plasma magnesium concentrations, and oxidative status were determined prior to, 24 hours and eight weeks after administration of the STZ. After eight weeks of treatment, the animals were anesthetized and sacrificed. The uterus and ovaries were removed and examined under optical microscopy. The data obtained were analyzed statistically using the ANOVA test. The results showed that the number of atretic ovarian follicles was 84%higher in the STZ-induced diabetes group compared to the control group (p<0.01). The number of atretic follicles found in the group receiving daily MgCl2 was 32% higher compared to the untreated control group (p<0.05). The number of atretic follicles was increased by only 27% in the metformin-treated group, as compared with the untreated control group.. The STZ-induced diabetes group presented an endometrial epithelial atrophy not seen in the control group. MgCl2 administration attenuated the degree of endometrial atrophy, there being an endometrial epithelial thickness of 19.43 ± 0.51 µm in the STZ+MgCl2 group (p<0.05), as compared to a thickness of 13.51 ± 0.27 µm in the STZ only-treated diabetic group.

A new method for the quantification of superoxide dismutase mimics with an allopurinol-xanthine oxidase-lucigenin enhanced system.

Allopurinol is a prodrug converted to oxypurinol by xanthine oxidase, a process followed by an efficient enzyme inhibition. Using a lucigenin-enhanced chemiluminescence method, we found that, under alkaline conditions, superoxide radicals are produced in large amounts in the first step of the interaction between the enzyme and the inhibitor. A comparison between lucigenin and cytochrome c as final detectors revealed that only the chemiluminescence technique is able to detect the superoxide anions from allopurinol oxidation. The allopurinol-xanthine oxidase-lucigenin system can be used for the quantification of various free-radical scavengers, in particular superoxide dismutase mimics. Three manganese compounds from different structural classes [manganese(II) chloride, manganese N,N'-bis(salicylidiene)ethylenediamine chloride, and manganese(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin] were compared at five concentrations (0.01, 0.1, 1, 10, and 100 µM). The method is fast, 16 times more sensitive than the cytochrome c assay at pH 10.1 and could be used for in vivo investigations avoiding the lucigenin redox cycle. If the concentrations of the reagents are increased and Tween 20 is added, the method is also operative at pH 7.4.

Magnesium in drug dependences.

Magnesium decreases the intensity of some drug-induced dependences (e.g. opiates, nicotine, cocaine, amphetamine, ethanol, etc.). The main mechanism involved is a decreasing activity of central glutamatergic synapses, especially those involved in the reward system. There are many particularities of action for each drug dependence. Apart from the effects during emerging dependence, magnesium ions administered only during the withdrawal syndrome decrease the intensity of clinical symptoms. In some cases, Mg2+ decreased the relapse and reinstatement of cocaine and amphetamine intake. Administered alone, in the absence of any abused drug, Mg2+ has moderate stimulatory effects on the reward system and reinforcement, without inducing dependence. The existent data stress a modulatory role of Mg2+ in some drug-induced dependences. Therapeutic administration of magnesium decreases nicotine dependence and cocaine/amphetamine self-administration.

Magnesium and other bivalent cations influence upon sodium montelukast effect in experimental-induced thermoalgesia.

We tested the influence of magnesium, zinc and copper upon the montelukast (MK, antagonist of cysteinyl leukotriene receptor type 1) effect in experimentally-induced thermoalgesia. We worked on 5 groups of 10 adults, each Wistar rats, that received: group I-control; group II: MK (10 mg/kg) unique administration; group III: MgCl2 (1 mM/kg/day) i.p., 3 days and MK (10 mg/kg) unique administration on the 3rd day; group IV: ZnCl2, (0.1 mM/kg/day), i.p., 3 days and MK (10 mg/kg) unique administration on the 3rd day; group V: copper acetate (0.05 mM/kg/day), i.p., 3 days and MK (10 mg/kg) unique administration on the 3rd day. We determined the thermoalgesic sensitivity (TS) using a tail flick analgesia meter, initially, 3 days after daily cation administration and 3 hours after MK administration. Our data show that MK has a statistically significant reduction of TS vs control group (3.76 +/- 1.04 s vs 1.81 +/- 0.98 s, p < 0.05). Copper and magnesium administration do not significantly change the MK effect to decrease TS. The co-administration of zinc and MK statistically significantly increased the TS of the group that received only MK (2.51 +/- 0.21 s vs 3.76 +/- 1.04 s, p < 0.05). Animals that received only cations (in the above mentioned doses) did not significantly change TS.

Effect of propranolol on mepivacaine serum concentrations in dental practice.

OBJECTIVE: The objective of this study was to determine the effect of propranolol pretreatment on mepivacaine serum concentrations in dental patients. STUDY DESIGN: In a double blind, randomized, 2-way crossover study, 10 patients ingested 30 mg propranolol or placebo, 2 hours before local anesthesia for dental scaling. Each subject received a single dose of 51 mg mepivacaine for posterior superior alveolar nerve block. Mepivacaine in venous serum was measured for up to 1 hour, after 5, 15, 30, 45, and 60 minutes from injection. Serum concentrations of mepivacaine were determined by gas chromatography. Blood pressure and heart rate were measured before and after propranolol or placebo and after each sampling. RESULTS: Peak serum concentrations of mepivacaine, C(max) (1.214 +/- 0.746 microg/mL(-1)), were significantly increased by propranolol (2.249 +/- 1.559 microg/mL(-1), P < .05). Propranolol pretreatment reduced blood pressure and heart rate. CONCLUSION: Although propranolol pretreatment increased almost doublefold mepivacaine serum concentrations and reduced blood pressure and heart rate, mepivacaine can be used safely in dental patients taking propranolol for short-duration interventions.

Blood plasma and saliva levels of magnesium and other bivalent cations in patients with parotid gland tumors.

The plasma and saliva cations in parotid malignant tumors of stages II-III were studied in 31 patients before surgical therapy and in 27 control group volunteers. The magnesium (t-Mg), calcium (t-Ca), copper (t-Cu) and zinc (t-Zn) concentrations in plasma were determined, and t-Mg and t-Ca in saliva. Our results showed that salivary and plasma t-Mg concentrations were significantly higher in patients with parotid malignant tumors in comparison to control group (saliva: 0.25 +/- 0.04 mmol/L versus 0.14 +/- 0.03/L, p < 0.01; plasma: 1.05 +/- 0.06 mmol/L versus 0.86 +/- 0.05 mmol/L, p < 0.05). The t-Ca plasma concentrations were lower for patients with parotid malignant tumors by 20-22% in comparison to the control group (p < 0.05). Plasma and salivary t-Mg/t-Ca molar ratios are respectively 0.38 and 0.12 for control group, and respectively 0.61 and 0.31 for patients with parotid gland tumors. The t-Zn plasma concentration for patients with parotid malignant tumors (0.017 +/- 0.010 mmol/L) was significantly lower (p < 0.05) in comparison to control group (0.024 +/- 0.011 mmol/L). Plasma t-Cu/t-Zn molar ratio is respectively 0.68 for control group and 1.12 for patients with parotid gland tumors. The mechanism responsible for the increase of salivary magnesium as a consequence of the development of tumoral tissue needs to be clarified.

Magnesium influence on nicotine pharmacodependence and smoking.

We followed the magnesium effect (Magne B(6)R, Sanofi-Synthelabo) with internal administration in 53 adult neurotic smoking patients (more than 10 cigarettes/day) of both genders admitted into psychiatric hospital. The nicotine dependence was assessed by the Fagerstrom test, initially and after 28 days of magnesium intake. Plasmatic magnesium level was determined before any therapy and at 28 days. All patients received benzodiazepines during the trial. Our data show that patients that received magnesium therapy showed a significant decrease in the number of cigarettes smoked and Fagerstrom test after 4 weeks [Fagerstrom score 7.93 +/- 0.17 before magnesium therapy versus 6.78 +/- 0.18 (P < 0.05) after 28 days of magnesium therapy]. In the group of smokers who did not receive magnesium, the Fagerstrom score did not change significantly [Fagerstrom score 7.48 +/- 0.22 initial versus 7.24 +/- 0.19 after 28 days]. Magnesium supplementation raised plasmatic levels (17.2 +/- 1.2 mg/L before versus 26.1 +/- 1.6 mg/L after 28 days of magnesium intake, P < 0.01). The results suggest that this cation might be a useful adjuvant in treatment of nicotine pharmacodependence.