Topical azole treatments for otomycosis.

BACKGROUND: Otomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole group ('azoles') being among the most widely used. OBJECTIVES: To evaluate the benefits and harms of topical azole treatments for otomycosis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 11 November 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults and children with otomycosis comparing any topical azole antifungal with: placebo, no treatment, another type of topical azole or the same type of azole but applied in different forms. A minimum follow-up of two weeks was required. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) clinical resolution as measured by the proportion of participants with complete resolution at between two and four weeks after treatment (however defined by the authors of the studies) and 2) significant adverse events. Secondary outcomes were 3) mycological resolution and 4) other less serious adverse effects. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included four studies with 559 participants from Spain, Mexico and India. Three studies included children and adults; one included only adults. The duration of symptoms was not always explicitly stated. Mycological resolution results were only reported in one study. The studies assessed two comparisons: one type of topical azole versus another and the same azole but administered in different forms (cream versus solution). A. Topical azoles versus placebo None of the studies assessed this comparison. B. Topical azoles versus no treatment None of the studies assessed this comparison. C. One type of topical azole versus another type of topical azole i) Clotrimazole versus other types of azoles (eberconazole, fluconazole, miconazole) Three studies examined clotrimazole versus other types of azoles. The evidence is very uncertain about the difference between clotrimazole and other types of azole in achieving complete clinical resolution at four weeks (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.07; 3 studies; 439 participants; very low-certainty evidence). The anticipated absolute effects are 668 per 1000 for clotrimazole versus 835 per 1000 for other azoles. One study planned a safety analysis and reported no significant adverse events in either group. The evidence is therefore very uncertain about any differences between clotrimazole and other types of azole (no events in either group; 1 study; 174 participants; very low-certainty evidence). Clotrimazole may result in little or no difference in mycological resolution at two weeks follow-up (RR 1.01, 95% CI 0.96 to 1.06; 1 study; 174 participants; low-certainty evidence) or in other (less serious) adverse events at two weeks follow-up (36 per 1000, compared to 45 per 1000, RR 0.79, 95% CI 0.18 to 3.41; 1 study; 174 participants; very low-certainty evidence). ii) Bifonazole cream versus bifonazole solution One study compared bifonazole 1% cream with solution. Bifonazole cream may have little or no effect on clinical resolution at two weeks follow-up when compared to solution, but the evidence is very uncertain (RR 1.07, 95% CI 0.73 to 1.57; 1 study; 40 ears; very low-certainty evidence). Bifonazole cream may achieve less mycological resolution compared to solution at two weeks after the end of therapy, but the evidence for this is also very uncertain (RR 0.53, 95% CI 0.29 to 0.96; 1 study; 40 ears; very low-certainty evidence). Five out of 35 patients sustained severe itching and burning from the bifonazole solution but none with the bifonazole cream (very low-certainty evidence). AUTHORS' CONCLUSIONS: We found no studies that evaluated topical azoles compared to placebo or no treatment. The evidence is very uncertain about the effect of clotrimazole on clinical resolution of otomycosis, on significant adverse events or other (non-serious) adverse events when compared with other topical azoles (eberconazole, fluconazole, miconazole). There may be little or no difference between clotrimazole and other azoles in terms of mycological resolution. It may be difficult to generalise these results because the range of ethnic backgrounds of the participants in the studies is limited.

Fear expression is reduced after acute and repeated nociceptin/orphanin FQ (NOP) receptor antagonism in rats: therapeutic implications for traumatic stress exposure.

RATIONALE: Evaluation of pharmacotherapies for acute stress disorder (ASD) or post-traumatic stress disorder (PTSD) is challenging due to robust heterogeneity of trauma histories and limited efficacy of any single candidate to reduce all stress-induced effects. Pursuing novel mechanisms, such as the nociceptin/orphanin FQ (NOP) system, may be a viable path for therapeutic development and of interest as it is involved in regulation of relevant behaviors and recently implicated in PTSD and ASD. OBJECTIVES: First, we evaluated NOP receptor antagonism on general behavioral performance and again following a three-species predator exposure model (Experiment 1). Then, we evaluated effects of NOP antagonism on fear memory expression (Experiment 2). METHODS: Adult, male rats underwent daily administration of NOP antagonists (J-113397 or SB-612,111; 0-20 mg/kg, i.p.) and testing in acoustic startle, elevated plus maze, tail-flick, and open field tests. Effects of acute NOP antagonism on behavioral performance following predator exposure were then assessed. Separately, rats underwent fear conditioning and were later administered SB-612,111 (0-3 mg/kg, i.p.) prior to fear memory expression tests. RESULTS: J-113397 and SB-612,111 did not significantly alter most general behavioral performance measures alone, suggesting minimal off-target behavioral effects of NOP antagonism. J-113397 and SB-612,111 restored performance in measures of exploratory behavior (basic movements on the elevated plus maze and total distance in the open field) following predator exposure. Additionally, SB-612,111 significantly reduced freezing behavior relative to control groups across repeated fear memory expression tests, suggesting NOP antagonism may be useful in dampening fear responses. Other measures of general behavioral performance were not significantly altered following predator exposure. CONCLUSIONS: NOP antagonists may be useful as pharmacotherapeutics for dampening fear responses to trauma reminders, and the present results provide supporting evidence for the implication of the NOP system in the neuropathophysiology of dysregulations in fear learning and memory processes observed in trauma- and stress-related disorders.

Modulation of the NOP receptor signaling affects resilience to acute stress.

BACKGROUND: The peptide nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are implicated in the modulation of emotional states. Previous human and rodent findings support NOP antagonists as antidepressants. However, the role played by the N/OFQ-NOP receptor system in resilience to stress is unclear. AIMS: The present study investigated the effects of activation or blockade of NOP receptor signaling before exposure to acute stress. METHODS: The behavioral effects of the administration before stress of the NOP agonists Ro 65-6570 (0.01-1 mg/kg) and MCOPPB (0.1-10 mg/kg), and the NOP antagonist SB-612111 (1-10 mg/kg) were assessed in mice exposed to inescapable electric footshock and forced swim as stressors. The behavioral phenotype of mice lacking the NOP receptor (NOP(-/-)) exposed to inescapable electric footshock was also investigated. RESULTS: The activation of NOP receptor signaling with the agonists increased the percentage of mice developing helpless behavior and facilitated immobile posture. In contrast, the blockade of NOP receptor reduced the acquisition of depressive-like phenotypes, and similar resistance to develop helpless behaviors was observed in NOP(-/-) mice. Under the same stressful conditions, the antidepressant nortriptyline (20 mg/kg) did not change the acquisition of helpless behavior and immobile posture. CONCLUSIONS: These findings support the view that NOP activation during acute stress facilitates the development of depressive-related behaviors, whereas NOP blockade has a protective outcome. This study showed for first time that NOP antagonists are worthy of investigation as preemptive treatments in patients with severe risk factors for depression.

Genetic and pharmacological evidence that endogenous nociceptin/orphanin FQ contributes to dopamine cell loss in Parkinson's disease.

To investigate whether the endogenous neuropeptide nociceptin/orphanin FQ (N/OFQ) contributes to the death of dopamine neurons in Parkinson's disease, we undertook a genetic and a pharmacological approach using NOP receptor knockout (NOP(-/-)) mice, and the selective and potent small molecule NOP receptor antagonist (-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111). Stereological unbiased methods were used to estimate the total number of dopamine neurons in the substantia nigra of i) NOP(-/-) mice acutely treated with the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), ii) naïve mice subacutely treated with MPTP, alone or in combination with SB-612111, iii) rats injected with a recombinant adeno-associated viral (AAV) vector overexpressing human mutant p.A53T α-synuclein, treated with vehicle or SB-612111. NOP(-/-) mice showed a 50% greater amount of nigral dopamine neurons spared in response to acute MPTP compared to controls, which was associated with a milder motor impairment. SB-612111, given 4 days after MPTP treatment to mimic the clinical condition, prevented the loss of nigral dopamine neurons and striatal dopaminergic terminals caused by subacute MPTP. SB-612111, administered a week after the AAV injections in a clinically-driven protocol, also increased by 50% both the number of spared nigral dopamine neurons and striatal dopamine terminals, and prevented accompanying motor deficits induced by α-synuclein. We conclude that endogenous N/OFQ contributes to dopamine neuron loss in pathogenic and etiologic models of Parkinson's disease through NOP receptor-mediated mechanisms. NOP receptor antagonists might prove effective as disease-modifying agents in Parkinson's disease, through the rescue of degenerating nigral dopamine neurons and/or the protection of the healthy ones.

The Efficacy and Safety of Eberconazole Nitrate 1% and Mometasone Furoate 0.1% w/w Cream in Subjects with Inflamed Cutaneous Mycoses.

BACKGROUND: Topical antifungal agents along with the steroids may provide not only rapid symptomatic relief but also clearance of disease causing fungi in inflamed cutaneous mycoses (ICM). AIM: To assess the efficacy and safety of fixed dose combination (FDC) of Eberconazole nitrate 1% and Mometasone furoate 0.1% w/w cream, in subjects with ICM. METHODS: This was a multi-centric, non-comparative study conducted in 155 eligible adult Indian subjects with ICM. They were treated with study medication for 21 days (D21) and followed up on day 35 (D35). Efficacy (by Investigator's Static Global Assessment-ISGA, symptom severity scores) and safety were assessed to evaluate the therapeutic response. RESULTS: Of 155 subjects, 129 completed the study. Lesions healed completely in 77.52% and improved markedly in 22.48% patients by D21. There was a statistically significant reduction (p<0.001) in total symptom score (TSS) and mean severity scores of erythema, scaling and pruritus on days 7 and 21 compared to baseline. There was no treatment failure. Only 11 patients remained culture positive on D21 compared to 68 at baseline. Physicians evaluated the drug as 'Good' in 72% and 'Excellent' in 28% of subjects; adverse events were reported in 27.74% subjects and none was severe. There was a decrease in serum cortisol level in 4.52% (7/155) subjects and was considered clinically significant in three subjects. On D35, 18.55% and 24.20% subjects had greater ISGA score and TSS respectively, compared to D21. CONCLUSION: Tested FDC demonstrated efficacy and was well tolerated by study population. It offers an effective and safe therapeutic option for the management of ICM.

Investigation of ethyl cellulose microsponge gel for topical delivery of eberconazole nitrate for fungal therapy.

BACKGROUND: The aim of the study was to investigate ethyl cellulose microsponges as topical carriers for the controlled release and cutaneous drug deposition of eberconazole nitrate (EB). MATERIALS & METHOD: EB microsponges were prepared using the quasiemulsion solvent diffusion method. The effect of formulation variables (drug:polymer ratio, internal phase volume and amount of emulsifier) and process variables (stirring time and stirring speed) on the physical characteristics of microsponges were investigated. The optimized microsponges were dispersed into a hydrogel and evaluated. RESULTS & DISCUSSION: Spherical and porous EB microsponge particles were obtained. The optimized microsponges possessed particle size, drug content and entrapment efficiency of 24.5 µm, 43.31% and 91.44%, respectively. Microsponge-loaded gels demonstrated controlled release, nonirritancy to rat skin and antifungal activity. An in vivo skin deposition study demonstrated fourfold higher retention in the stratum corneum layer as compared with commercial cream. CONCLUSION: Developed ethyl cellulose microsponges could be potential pharmaceutical topical carriers of EB in antifungal therapy.

Ferutinin dose-dependent effects on uterus and mammary gland in ovariectomized rats.

The present paper completes our recent study on the effects of phytoestrogen ferutinin in preventing osteoporosis and demonstrating the superior osteoprotective effect of a 2 mg/kg/day dose in ovariectomized (OVX) rats, compared to both estrogens and lower (0.5, 1 mg/kg/day) ferutinin doses. Morphological and morphometrical analyses were performed on the effects of different doses of ferutinin administrated for one month on uterus and on mammary gland of Sprague-Dawley OVX rats, evaluated in comparison with the results for estradiol benzoate. To verify whether ferutinin provides protection against uterine and breast cancer, estimations were made of both the amount of cell proliferation (by Ki-67), and the occurrence of apoptosis (by TUNEL), two processes that in unbalanced ratio form the basis for cancer onset. The results suggest that the effects of ferutinin are dose dependent and that a 2 mg/kg/day dose might offer a better protective action against the onset of both breast and uterine carcinoma compared to ferutinin in lower doses or estradiol benzoate, increasing cellular apoptosis in glandular epithelia.

Acute and chronic antiparkinsonian effects of the novel nociceptin/orphanin FQ receptor antagonist NiK-21273 in comparison with SB-612111.

BACKGROUND AND PURPOSE: Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonists have been proposed as a novel therapeutic approach to Parkinson's disease. Main limitations of previous studies were the use of structurally similar compounds and the evaluation of their acute effects only. We report here on the acute and long-term antiparkinsonian effects of the novel compound 2-[3-[4-(2-chloro-6-fluoro-phenyl)-piperidin-1-ylmethyl]-2-(morpholine-4-carbonyl)-indol-1-yl]-acetamide (NiK-21273) in comparison with the potent and selective NOP receptor antagonist SB-612111. EXPERIMENTAL APPROACH: Basic pharmacological properties of NiK-21273 were studied in cell lines and isolated tissues (mouse and rat vas deferens). Antiparkinsonian effects were studied in reserpinized mice and 6-hydroxydopamine hemilesioned rats under both acute and chronic administration protocols. KEY RESULTS: In vitro, NiK-21273 behaved as a potent (pA(2) 7.7) and selective NOP receptor antagonist. In vivo, it reduced hypokinesia in reserpinized mice at 0.1 and 1 but not 10 mg·kg(-1), whereas SB-612111 (0.01-1 mg·kg(-1)) provided a dose-dependent antiparkinsonian effect. NiK-21273 ameliorated motor performance in 6-hydroxydopamine hemilesioned rats at 0.5 and 5 but not 15 mg·kg(-1). SB-612111 replicated these effects in the 0.01-1 mg·kg(-1) range without loss of efficacy. Both antagonists synergized with L-DOPA at subthreshold doses. Chronic administration of NiK-21273 provided delayed improvement in baseline activity at 0.5 and 1.5 mg·kg(-1), although tolerance to the higher dose was observed. Conversely, SB-612111 (1 mg·kg(-1)) maintained its effects over time without modifying baseline activity. CONCLUSIONS AND IMPLICATIONS: NOP receptor antagonists provide motor benefit in parkinsonism models although the 'therapeutic' window and long-term effects may vary between compounds.

Effects of different doses of ferutinin on bone formation/resorption in ovariectomized rats.

This study analyzes the effects of different doses of ferutinin on bone loss caused by estrogen deficiency in ovariectomized rats, in comparison with estradiol benzoate. Thirty female Sprague-Dawley rats were ovariectomized and treated for 30 days from the day after ovariectomy. Static/dynamic histomorphometric analyses were performed on trabecular and cortical bone of lumbar vertebrae and femurs. Very low weight increments were recorded only in all F-OVX groups, with respect to the others. Although the great differences in weight, that could imply a decrease of bone mass in F-OVX groups compared to the control ovariectomized group (C-OVX), trabecular bone in lumbar vertebrae did not show significant differences, suggesting that ferutinin, opposing estrogen deficiency, inhibits bone resorption. Newly formed cortical bone was always low in all F-OVX groups and high in C-OVX, suggesting that it is mainly devoted in answering mechanical demands. In contrast, in distal femoral metaphyses, trabecular bone was reduced and the number of osteoclasts was increased in C-OVX with respect to all other groups, suggesting that it is mainly devoted in answering metabolic demands; moreover, ferutinin dose of 2 mg/kg seemed to be more effective than the lower doses used and estrogens, particularly in those skeletal regions with higher metabolic activity. Our results suggest that the role of ferutinin in preventing osteoporosis caused by estrogen deficiency is expressed in decreasing bone erosion; moreover, in all F-OVX groups bone turnover is very low and seems correlated to the trivial body weight increase, which, in turn, depends on ferutinin treatment.

Brain and whole-body imaging in rhesus monkeys of 11C-NOP-1A, a promising PET radioligand for nociceptin/orphanin FQ peptide receptors.

UNLABELLED: Our laboratory developed (S)-3-(2'-fluoro-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran]-1-yl)-2-(2-fluorobenzyl)-N-methylpropanamide ((11)C-NOP-1A), a new radioligand for the nociceptin/orphanin FQ peptide (NOP) receptor, with high affinity (K(i), 0.15 nM) and appropriate lipophilicity (measured logD, 3.4) for PET brain imaging. Here, we assessed the utility of (11)C-NOP-1A for quantifying NOP receptors in the monkey brain and estimated the radiation safety profile of this radioligand based on its biodistribution in monkeys. METHODS: Baseline and blocking PET scans were acquired from head to thigh for 3 rhesus monkeys for approximately 120 min after (11)C-NOP-1A injection. These 6 PET scans were used to quantify NOP receptors in the brain and to estimate radiation exposure to organs of the body. In the blocked scans, a selective nonradioactive NOP receptor antagonist (SB-612111; 1 mg/kg intravenously) was administered before (11)C-NOP-1A. In all scans, arterial blood was sampled to measure the parent radioligand (11)C-NOP-1A. Distribution volume (V(T); a measure of receptor density) was calculated with a compartment model using brain and arterial plasma data. Radiation-absorbed doses were calculated using the MIRD Committee scheme. RESULTS: After (11)C-NOP-1A injection, peak uptake of radioactivity in the brain had a high concentration (∼5 standardized uptake value), occurred early (∼12 min), and thereafter washed out quickly. V(T) (mL · cm(-3)) was highest in the neocortex (∼20) and lowest in hypothalamus and cerebellum (∼13). SB-612111 blocked approximately 50%-70% of uptake and reduced V(T) in all brain regions to approximately 7 mL · cm(-3). Distribution was well identified within 60 min of injection and stable for the remaining 60 min, consistent with only parent radioligand and not radiometabolites entering the brain. Whole-body scans confirmed that the brain had specific (i.e., displaceable) binding but could not detect specific binding in peripheral organs. The effective dose for humans estimated from the baseline scans in monkeys was 5.0 µSv/MBq. CONCLUSION: (11)C-NOP-1A is a useful radioligand for quantifying NOP receptors in the monkey brain, and its radiation dose is similar to that of other (11)C-labeled ligands for neuroreceptors. (11)C-NOP-1A appears to be a promising candidate for measuring NOP receptors in the human brain.

The phytoestrogen ferutinin affects female sexual behavior modulating ERalpha expression in the hypothalamus.

This study was designed to assess the effect of the phytoestrogenic compound ferutinin, chronically administered in ovariectomized progesterone primed rats, alone or in combination with estradiol benzoate. After 2, 3 and 4 weeks of treatments, female rats were tested for receptive (lordosis) and proceptive behaviors (hops, darts and ear wigglings). Ferutinin given alone markedly increased the intensity of the lordotic response in ovariectomized rats but failed to significantly affect proceptivity. On the other hand estradiol benzoate significantly increased both receptive and proceptive behaviors. When administered in combination with estradiol, ferutinin reduced the increase in receptivity and proceptivity due to estrogen effects, acting as an antiestrogen. At the end of the behavioral experiments, animals were sacrificed and Western blot analysis of estrogen receptor alpha (ERalpha) levels was performed in the dissected hypothalami. Ferutinin increased ERalpha expression when administered alone, as estradiol did, but decreased the response to estradiol when administered in combination. These results suggest that ferutinin displays estrogenic or antiestrogenic activity through ERalpha in the hypothalamus, depending on the absence or the presence of estrogen priming.

Eberconazole 1% cream is an effective and safe alternative for dermatophytosis treatment: multicenter, randomized, double-blind, comparative trial with miconazole 2% cream.

BACKGROUND: Eberconazole is a topical, broad-spectrum imidazole derivative, effective in dermatophytoses, candidiasis, and pityriasis treatment. In previous trials, it showed a higher efficacy than clotrimazole in the treatment of dermatophytoses. The purpose of this trial was to evaluate the efficacy of eberconazole 1% cream compared with miconazole 2% cream in the treatment of dermatophytoses. METHODS: A multicenter, double-blind, randomized trial was performed in 653 patients with dermatophytoses, randomized to eberconazole 1% cream every 12 h or miconazole 2% cream every 12 h for 4 weeks. Treatment efficacy was assessed on the basis of the percentage of effective response after 4 weeks through mycologic and clinical assessment. RESULTS: Of the 653 patients included in the trial, 360 produced positive baseline mycologic cultures and were included in the efficacy assessment. Clinical efficacy was shown in 76.1% of patients receiving eberconazole and in 75.0% of patients receiving miconazole. The incidence of adverse events related to treatment was 0.91% for eberconazole and 0.92% for miconazole, none being serious, and all being local and transient. CONCLUSIONS: Eberconazole 1% cream is an effective treatment for fungal infections produced by dermatophytes, with a good safety and tolerability profile, and can be considered a good alternative for the treatment of dermatophytoses.

Azulene incorporation and release by hydrogel containing methacrylamide propyltrimenthylammonium chloride, and its application to soft contact lens.

We have developed the epoch-making contact lens that is equipped with drug delivery system. The hydrogels contain cationic functional group in its side chain were prepared with 2-hydroxyethyl methacylate (HEMA) and methacrylamide propyltrimethylammonium chloride (MAPTAC). The obtained hydrogel is capable to store the anionic drug such as azulene based on ion-exchange reaction. The incorporated anionic drug would be released in physiological condition. The size change of the hydrogel may occur before and after drug release, but we have discovered that the addition of anionic monomer such as methacrylic acid (MAA) and 2-methacryloxyethyl acid phosphate (MOEP) to the above-mentioned composition is effective to prevent the size change, indicating that this hydrogel has the possibility to be applied as a significant drug delivery system device.

In vitro anti-multidrug resistance activities of acyclic and cyclic disulfonamides in murine leukemia cells.

We synthesized seven acyclic ethylenedisulfonamides and twelve cyclic disulfonamides, 1, 5-bis(arenesulfonyl)-1, 3, 5-triazacycloheptanes, and compared their in vitro anti-multidrug resistance effects in P388/ADR multidrug-resistant cells which overexpress the multidrug transporter P-glycoprotein (P-gp). Acyclic disulfonamides with 4-methoxyphenyl, pyridyl, quinolyl, or isoquinolyl groups hardly influenced the sensitivity of P388/ADR cells to vinblastine (VLB), and cyclic disulfonamides with these aryl groups only slightly increased the sensitivity to VLB. Acyclic or cyclic disulfonamides with 4-chlorophenyl or naphthyl groups moderately potentiated the effect of VLB. The maximum effect was observed with 1, 5-bis(1-naphthale-nesulfonyl)-1, 3, 5-triazacycloheptan (B3). B3 enhanced the effects of vincristine, adriamycin, daunomycin and actinomycin D in P388/ADR cells, but not in sensitive P388 cells. B3 increased intracellular concentrations of VLB and adriamycin in P388/ADR cells. The expression of P-gp in P388/ADR cells was not affected by cultivation with B3 for 72 hours. These results indicated that the anti-multidrug resistance activities of B3 were dependent on its inhibitory effect on P-gp.

Effect of marzulene on the restitution of rat gastric mucosa after NaOH-induced injury.

BACKGROUND/AIMS: The purpose of this study was to assess the effect of marzulene (L-glutamine plus azulene) on the repair of NaOH-induced gastric mucosal injury in rats. METHODOLOGY: Gastric mucosal injury was induced with intragastric instillation of 3.0 ml of 5% NaOH for 1 minute. From 2 days after the operation, the rats were orally given chow pellets containing 0%, 0.25%, or 0.5% of marzulene for 25 weeks. RESULTS: Oral administration of marzulene at both dosages significantly increased the mucosal heights of the fundic and antral mucosa at week 25. Marzulene also increased the labeling indices of the fundic and antral epithelial cells, but not the mucosal blood flow. CONCLUSIONS: These findings indicate that marzulene stimulates repair mechanisms of rat gastric mucosa after NaOH injury. This effect of marzulene may be associated with a stimulation of gastric epithelial cell proliferation.

Influence of aging on the acute depletion of reduced glutathione induced by electrophilic agents.

A severe age-dependent depletion of reduced glutathione (GSH) occurs in rat forebrain at 1-3 h from intraperitoneal injection of the electrophilic agents cyclohexene-1-one and cycloheptene-1-one. Chronic pretreatment with central dopamine agonists (i.e., ergot alkaloids; particularly, dihydroergocriptine) partially counteracts the GSH depletion induced in 15-month-old forebrains by the prooxidants tested. In contrast, chronic pretreatment with a vasodilator agent (i.e., papaverine) magnifies the GSH depletion.

[Bencyclane in stage II arterial occlusive disease. Results of a controlled study]. / Bencyclan bei arterieller Verschlusskrankheit im Stadium II. Ergebnisse einer kontrollierten Studie.

In a single-center, double-blind, randomized study, 19 patients with peripheral arterial occlusive disease stage II Fontaine were treated with bencyclan, and a further 19 patients with buflomedil for 10 weeks after a wash-out phase of 2 weeks. Both groups showed a significant increase in painfree and total walking distances. No significant difference was found between the two groups.