Montelukast Influence on Lung in Experimental Diabetes.

Background and Objectives: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. Materials and Methods: The study was conducted on four groups of six adult male Wistar rats. Diabetes was produced by administration of streptozotocin 65 mg/kg ip. in a single dose. Before the administration of streptozotocin, after 72 h, and after 8 weeks, the serum values of glucose, SOD, MDA, and total antioxidant capacity (TAS) were determined. After 8 weeks, the animals were anesthetized and sacrificed, and the lungs were harvested and examined by optical microscopy. Pulmonary fibrosis, the extent of lung lesions, and the lung wet-weight/dry-weight ratio were evaluated. Results: The obtained results showed that MK significantly reduced pulmonary fibrosis (3.34 ± 0.41 in the STZ group vs. 1.73 ± 0.24 in the STZ+MK group p < 0.01) and lung lesion scores and also decreased the lung wet-weight/dry-weight (W/D) ratio. SOD and TAS values increased significantly when MK was administered to animals with diabetes (77.2 ± 11 U/mL in the STZ group vs. 95.7 ± 13.3 U/mL in the STZ+MK group, p < 0.05, and 25.52 ± 2.09 Trolox units in the STZ group vs. 33.29 ± 1.64 Trolox units in the STZ+MK group, respectively, p < 0.01), and MDA values decreased. MK administered alone did not significantly alter any of these parameters in normal animals. Conclusions: The obtained data showed that by blocking the action of peptide leukotrienes on cysLT1 receptors, montelukast significantly reduced the lung lesions caused by diabetes. The involvement of these leukotrienes in the pathogenesis of fibrosis and other lung diabetic lesions was also demonstrated.

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.

Importance of Magnesium Status in COVID-19.

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted.

Assessment and outcome of hospitalized patients during delta variant COVID-19 pandemic: A multicenter international study.

INTRODUCTION: To date, the world has experienced four waves of the Coronavirus disease- 19 (COVID-19) pandemic. Patients infected during the era of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant were the subject of this study. The objectives were to describe their clinical manifestations, explain their laboratory and radiological findings, conclude factors contributing to clinical outcomes, and evaluate treatment protocols. METHODOLOGY: Relevant data were collected retrospectively from records of patients admitted to six referral centers in four countries. Data included sociodemographic patterns, symptoms, associated comorbidities, physical examination, laboratory and radiologic findings, treatment received, and patient outcomes. RESULTS: Data analysis identified symptomatology and variables related to acquisition and infection outcome. The most prevalent symptoms were cough (81.5%), body aches (74.1%), and fever (71.6%). Independent risk factors for mortality were age, vomiting, epigastric pain, diabetes, obesity, oxygen saturation less than 90%, leukocytosis, neutrophilia, lymphopenia, thrombocytopenia, elevated creatinine, high glucose level, lung ground glass opacities with consolidation, affection of four lobes and bilateralism. Neither d-dimer nor lactate dehydrogenase nor ferritin foretells death possibility. The efficacy of the medications used was convenient. CONCLUSIONS: Assessing the clinical features of different COVID-19 waves, identifying predictors of outcomes, and concluding the efficacy of treatment protocols provide insight into patients' responses and viral behaviors, which help in the proper diagnosis and treatment of subsequent surges.

Recommendation on an updated standardization of serum magnesium reference ranges.

PURPOSE: Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization. METHODS: We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide. RESULTS: Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD. CONCLUSIONS: Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

RT- PCR testing of upper respiratory tract samples for diagnosis of SARS-CoV-2: Between justification and overestimation, a multi-center international study.

BACKGROUND: It has been found that patients recovered from COVID 19 may still test Reverse Transcriptase- Polymerase Chain Reaction (RT- PCR) positive without being infectious; the reasons are unclear. The occurrence of false-negative results of RT- PCR interferes with a proper diagnosis. The objectives of that work were to determine factors associated with persistently detectable SARS-CoV-2 RNA among recovered hospitalized patients and to determine the incidence of false-negative RT-PCR results and associated factors. METHODS: Relevant data were collected from 482 COVID 19 patients hospitalized in six referral centers from four countries. RESULTS: The median duration of RT- PCR conversion to negative was 20 days. Out of 482 studied patients, 8.7% tested positive after more than four weeks and were considered prolonged convertors. Binary logistic regression analysis revealed headache as an independent risk factor for short conversion time while fever, hypertension, chronic obstructive pulmonary disease, lymphopenia, elevated erythrocyte sedimentation rate, and the number of lobes affected, and bilateralism were found to be independent risk factors for prolonged positivity. Eighteen patients had initial negative results then turned positive after 24-48 h. Associated factors and outcomes were identified. CONCLUSION: Identifying patients with a high likelihood of COVID-19 despite a negative RT-PCR is critical for effective clinical care. However, patient isolation resumption depending on positive RT-PCR despite clinical and radiological recovery is an overrating that greatly burdens the health sector.

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.

Chromium picolinate reduces morphine-dependence in rats, while increasing brain serotonin levels.

Chromium is an essential trace element with anti-diabetic and anti-depressant effect; the latter is considered related to chromium properties of increasing brain serotonin. Cr3+ salts were shown to improve some forced swimming-parameters and to induce rewarding effects, which are additive to those of morphine, but Cr effect on addictive processes has not been tested. AIM: The present study aimed to assess chromium picolinate (CrPi) influence on morphine-dependence in rats. MATHERIAL AND METHODS: We used five groups of 10 rats. Groups 1 and 2 (controls) received saline, respectively CrPi, 0.01 mg/kg/day, for 10 days. In groups 3, 4 and 5 dependence was induced with progressively-increased morphine doses (from 5 - day 1-90 mg/kg/day - day 10, s.c.). Group 3 received only morphine, while groups 4 and 5 received CrPi, i.p., 10 and respectively 5 µg/kg/day, during the 10 days of dependence induction. On day 11, groups 3, 4, and 5 were administered 90 mg/kg morphine, and, 2 h later, all rats received naloxone, 2 mg/kg s.c., to precipitate withdrawal. We compared withdrawal intensity in group 3 vs. groups 4 and 5, assessing both individual symptoms and Gellert-Holtzman global withdrawal score. Upon rats sacrifice at the end of the experiments, brain serotonin (5HT) in certain areas and serum Cr were assessed. RESULTS: Some withdrawal signs were unequally influenced by CrPi: compulsive mastication was reduced by both CrPi doses (p < 0.05), while teeth chattering and grooming were significantly reduced only by the higher dose (p < 0.05). Withdrawal score was reduced by both CrPi doses: from 132.4 ±â€¯9.87 - group 3 to 122.2 ±â€¯6.47 - group 4 (p < 0.01 vs. group 3) and 124.1 ±â€¯8.41 - group 5 (p < 0.05 vs. group 3). CrPi reduction of withdrawal is accompanied by increased brain 5 H T, mainly in the prefrontal cortex (646.3 ±â€¯8.51 - group 3 vs. 661.5 ±â€¯14.63 - group 4, p < 0.01 and 660.7 ±â€¯14.01 pg/mg tissue - group 5, p < 0.05 vs. group 3). CrPi also increases brain 5 H T in non-dependent rats (prefrontal cortex: 541.6 ±â€¯31.80, group 1 and 565.5 ±â€¯16. 46 pg/mg tissue, group 2, p < 0.05). Administration of CrPi determined a dose-dependent increase of serum Cr. CONCLUSIONS: Our study evidenced a slight, but significant reduction of morphine dependence in rats induced by chromium picolinate, accompanied by increased brain serotonin. This might be considered a supplementary evidence for chromium anti-depressant effect and its serotonin-mediated mechanisms.

Magnesium in addiction - a general view.

Addiction is a dysregulation of brain reward systems that progressively increases, resulting in compulsive drug use and loss of control over drug-taking. Addiction is a brain disease. There is evidence that magnesium deficit is involved in addiction to various addictive substances (heroin, morphine, cocaine, nicotine, alcohol, caffeine, and others). Magnesium is involved in all the stages of addiction. Magnesium deficit enhances the vulnerability to psychoactive substance addiction. Stress and trauma reduce the brain magnesium level and at the same time favor addiction development. In experimental studies, administration of magnesium while inducing morphine dependence in rats reduced the dependence intensity. Magnesium reduces the NMDA receptor activity and the glutamatergic activity. Because stress and trauma induce hypomagnesemia with increased vulnerability to addiction, magnesium intake by people who are under prolonged stress could be a way to reduce this vulnerability and the development of addiction to different psychoactive substances. Anxiety and depression appear to be associated with increases in drug-related harm and addictive substance use. Magnesium anxiolytic effect could be important for the antiaddictive action. Addiction is characterized by relapses. Magnesium deficiency may be a contributing factor to these relapses.

Hydrocephalus and vasculitis delay therapeutic responses in tuberculous meninigitis: Results of Haydarpasa-III study.

AIMS: There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. MATERIALS AND METHODS: This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. RESULTS: In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27-86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for >9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68-19.57]). According to linear regression analysis, fever was significantly persisting (>7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. CONCLUSIONS: In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.

Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study.

Predicting unfavorable outcome is of paramount importance in clinical decision making. Accordingly, we designed this multinational study, which provided the largest case series of tuberculous meningitis (TBM). 43 centers from 14 countries (Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria, Turkey) submitted data of microbiologically confirmed TBM patients hospitalized between 2000 and 2012. Unfavorable outcome was defined as survival with significant sequela or death. In developing our index, binary logistic regression models were constructed via 200 replicates of database by bootstrap resampling methodology. The final model was built according to the selection frequencies of variables. The severity scale included variables with arbitrary scores proportional to predictive powers of terms in the final model. The final model was internally validated by bootstrap resampling. A total of 507 patients' data were submitted among which 165 had unfavorable outcome. Eighty-six patients died while 119 had different neurological sequelae in 79 (16%) patients. The full model included 13 variables. Age, nausea, vomiting, altered consciousness, hydrocephalus, vasculitis, immunosuppression, diabetes mellitus and neurological deficit remained in the final model. Scores 1-3 were assigned to the variables in the severity scale, which included scores of 1-6. The distribution of mortality for the scores 1-6 was 3.4, 8.2, 20.6, 31, 30 and 40.1%, respectively. Altered consciousness, diabetes mellitus, immunosuppression, neurological deficits, hydrocephalus, and vasculitis predicted the unfavorable outcome in the scoring and the cumulative score provided a linear estimation of prognosis.

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.

Surveillance, control and management of infections in intensive care units in Southern Europe, Turkey and Iran--a prospective multicenter point prevalence study.

OBJECTIVE: We aimed to compare the features of intensive care units (ICUs), their antimicrobial resistance patterns, infection control policies, and distribution of infectious diseases from central Europe to Mid-West Asia. METHODS: A cross-sectional point prevalence study was performed in 88 ICUs from 12 countries. Characteristics of ICUs, patient and antibiotic therapy data were collected with a standard form by infectious diseases specialists. RESULTS: Out of 749, 305 patients at least with one infectious disease were assessed and 254 patients were reported to have coexistent medical problems. When primary infectious diseases diagnoses of the patients were evaluated, 69 had community-acquired, 61 had healthcare-associated, and 176 had hospital-acquired infections. Pneumonia was the most frequent ICU infection seen in half of the patients. Distribution of frequent pathogens was as follows: Enteric Gram-negatives (n = 62, 28.8%), Acinetobacter spp. (n = 47, 21.9%), Pseudomonas aeruginosa (n = 29, 13.5%). Multidrug resistance profiles of the infecting microorganisms seem to have a uniform pattern throughout Southern Europe and Turkey. On the other hand, active and device-associated infection surveillance was performed in Turkey more than Iran and Southeastern Europe (p < 0.05). However, designing antibiotic treatment according to culture results was highest in Southeastern Europe (p < 0.05). The most frequently used antibiotics were carbapenems (n = 92, 30.2%), followed by anti-gram positive agents (vancomycin, teicoplanin, linezolid, daptomycin, and tigecycline; n = 79, 25.9%), beta-lactam/beta lactamase inhibitors (n = 78, 25.6%), and extended-spectrum cephalosporins (n = 73, 23.9%). CONCLUSION: ICU features appears to have similar characteristics from the infectious diseases perspective, although variability seems to exist in this large geographical area.

The influence of oral steroidal contraceptives on magnesium concentration in breast milk.

This study determined the total magnesium concentration in the breast milk of mothers that were using oral, steroidal contraceptives during lactation. The study involved two groups of breast-feeding mothers that were receiving oral contraception, and a control group of 15 breast-feeding mothers that did not receive oral contraception. The first group received a daily combination pill (levonorgestrel 0.15 mg + ethinylestradiol 0.03 mg); the second group received a daily mini-pill (progestin-only pill, containing norethindrone 0.35 mg). The total magnesium concentrations of plasma and breast milk were determined before the start of contraception and after 30 days of contraception. The results showed that after 30 days of contraception, the contraceptive drugs had not significantly modified the total breast milk magnesium concentration (1.16 ± 0.11 mmol/L before treatment versus 1.01 ± 0.12 mmol/L, in first group; 0.97 ± 0.16 mmol/L before contraception versus 1.08 ± 0.11 mmol/L, in the second group). There were no significant changes in the total magnesium concentration in the breast milk of the control group after the 30 days. In addition, the oral, steroidal contraceptives (pill and mini-pill) did not affect the total magnesium concentration in the plasma of lactating mothers.

Effects of some dopamine agents on modulation of memory processes performance in rats.

UNLABELLED: Apomorphine is a potent dopamine receptor agonist which has been used as a neuro-protective agent in the treatment of Parkinson's disease. SCH-23390 is a synthetic compound that presents selective D1 dopamine receptors antagonist activity and possesses pharmacologic effects similar to standard antipsychotics. AIM: Experimental researches on the effects of two substances acting on dopamine receptors on the cognitive processes in rats. MATERIAL AND METHODS: The experiment was carried out on white male Wistar rats (150-200 g) divided into 3 groups of 6 animals each, treated intraperitonealy with the same volume of solution as follows: Group I (Control): saline solution 0.3 ml; Group II (coded APO): apomorphine 2 mg/kbw; Group III (coded SCH): SCH-23390 0.3 mg/kbw. Working memory was assessed using the radial-arm maze. The following measures were recorded: the number of entering an arm containing food, but previously entered (working memory errors); the number of entering an arm that was not baited (reference memory errors); time taken to consume all five baits and the number of arms entered until a repeat entry was made (entries to repeat). The data were presented as mean +/- standard deviation and significance was tested by SPSS Statistics for Windows version 17.0 and ANOVA method. Experimental protocol was implemented according to the recommendations of the "Grigore T. Popa" University Committee for Research and Ethical Issues. RESULTS: In our experimental conditions dopamine agonist apomorphine produced significantly (p < 0.05) more novel choices in the first eight-arm entries than the saline vehicle. The animals treated with apomorphine entered significantly (P < 0.05) more arms compared to the control group. D1 receptor antagonist SCH-23390 induced a significant decrease (p < 0.05) in the number of working memory errors (elements relevant for short-time memory quantification) and average time taken to consume all five baits (p < 0.05), but did not modify the number of reference memory errors (for long-time memory quantification) compared to the control group, suggesting a short-time memory retention enhancement and an improvement of discriminative spatial learning. SCH-23390 administration resulted in a not quite significant increase in the number of entries to repeat compared to control rats. CONCLUSIONS: The administration of apomorphine also increased the search efficiency in total arm entries, suggesting that it facilitates the response in the test session of secondary reinforcement, more than rewarding, effect combined with a lack of discrimination. Our research revealed that D1 receptor antagonist SCH-23390 influenced short-time memory, without affecting long-time memory of experimented animals.

Manganese SOD mimics are effective against heat stress in a mutant fission yeast deficient in mitochondrial superoxide dismutase.

UNLABELLED: Previous studies revealed a close connection between heat shock and manganese-dependent superoxide dismutase (SOD2) in eukaryotes. This paper shows that SOD mimics based on manganese complexes caused an increase in thermotolerance for a mutant fission yeast deficient in mitochondrial superoxide dismutase. Manganese compounds used for tests are SOD mimics, from two different classes: salen manganese (EUK-8) and Mn porphyrin (Mn(III)TE-2-PyP(5+)). The tests were conducted using a Schizosaccharomyces pombe model, comparing the viability of two strains at chronic heat stress (37°C)--a wild type versus a strain with the mitochondrial superoxide dismutase gene deleted [SOD2(-)]. The presence of massive free radical species in S. pombe SOD2(-) was demonstrated using a luminol-enhanced chemiluminescence test derived from a menadione-mediated survival protocol. CONCLUSIONS: Survival tests revealed that the SOD2-deleted S. pombe is about 100 times more sensitive to heat stress than the wild-type strain. This survival deficit can be corrected by EUK-8 and Mn(III)TE-2-PyP(5+) to almost the same degree but not by manganese chloride II (MnCl(2)). Using a simple spot assay for viability testing, this new model proved to be an easy alternative for the initial estimation of manganese SOD mimics efficiency.

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.

Influence of therapy with metformin on the concentration of certain divalent cations in patients with non-insulin-dependent diabetes mellitus.

Research was performed on a group of 30 patients with non-insulin-dependent diabetes mellitus (NIDDM), who never received antidiabetic medication before, and on a group of 17 healthy adults. The patients were administered treatment with metformin, 1,000 mg/day. Plasmatic and urinary concentration of magnesium have been measured, copper and zinc along with the concentrations of glucose, HDL, LDL, cholesterol, tryglicerides, HbA1c, and total erythrocyte magnesium, in advance and after 3 months of treatment. Data showed significant differences in the NIDDM group vs the control group: for plasma magnesium-1.95 ± 0.19 vs 2.20 ± 0.18 mg/dl, p < 0.001; urine magnesium-237.28 ± 34.51 vs 126.25 ± 38.22 mg/24 h, p < 0.001; erythrocyte magnesium-5.09 ± 0.63 vs 6.38 ± 0.75 mg/dl, p < 0.001; plasma zinc-67.56 ± 6.21 vs 98.41 ± 20.47 µg/dl, p < 0.001; urine zinc-1,347.54 ± 158.24 vs 851.65 ± 209.75 µg/24 h, p < 0.001; plasma copper-111.91 ± 20.98 vs 96.33 ± 8.56 µg/dl, p < 0.001; and urine copper-51.70 ± 23.79 vs 36.00 ± 11.70 µg/24 h, p < 0.05. Treatment with metformin for 3 months modified significant erythrocyte magnesium-5.75 ± 0.61 vs 5.09 ± 0.63 mg/dl, p < 0.001 and urine magnesium-198.27 ± 27.07 vs 237.28 ± 34.51 mg/24 h, p < 0.001, whereas it did not modify significant the plasmatic and urinary concentration of the other cations. The erythrocyte magnesium concentration was inversely correlated with HbA1c (r = -0.438, p = 0.015). The plasma level of copper was positively correlated with HbA1c (r = 0.517, p < 0.003), tryglicerides (r = 0.534, p < 0.003), and cholesterol (r = 0.440, p < 0.05), and the plasma level of zinc was inversely correlated with glycemia (r = -0.399, p = 0.029). Our data show a significant action of metformin therapy, by increasing the total intraerythrocyte magnesium concentration and decreasing the urinary magnesium elimination, positively correlated with the decrease of glycemia and HbA1c in NIDDM patients.