Role of Memantine in Limiting Cochleotoxicity in Rats.

Οur aim was to test whether amikacin's well-known cochleotoxic effects could be suppressed, depending on whether an NMDA-antagonist (memantine) was administered simultaneously with or after amikacin treatment. Forty Wistar rats were used in this experiment. Ten rats acted as controls and received no medication (group A). Amikacin (200 mg/kg) was administered intraperitoneally (i.p.) once daily for 14 days to 10 animals in group B; amikacin (200 mg/kg) was administered concurrently with memantine (10 mg/kg, i.p., once daily) to the same 10 animals in group C. Group D was given intraperitoneal memantine (10 mg/kg, once daily) for 14 days following a 2-week amikacin treatment. The cochlear activity of the right ear was tested using DPOAE in conscious animals. All animals were sacrificed at the conclusion of the experiment and both cochleae were collected for histological and immunohistochemical analysis. All groups treated with amikacin showed decreased cochlear activity, as testified by decreased DPOAE-amplitudes compared to the pre-treatment state. In the rats of group B, the DPOAE reduction was more pronounced. On histologic exam, the cochlear structures of group C rats and, although to a lesser extent, group D rats showed less severe cochlea damage. Memantine plays a protective role, resulting in restoring partially cochlear structures when administered either simultaneously with or after completion of amikacin i.p. treatment in rats.

Salicylate- and Noise-induced Tinnitus. Different Mechanisms Producing the same Result? An Experimental Model.

PURPOSE: Tinnitus, the generation of phantom sounds, can be the result of noise exposure, however, understanding of its underlying mechanisms is limited. Purpose of the study was is to determine whether different concentrations of salicylate can cause tinnitus of different intensity. METHODS: For the purposes of this study 50 male Wistar rats were used. The animals were divided into 5 groups (10 rats in each group). The animals that did not receive any substance were allocated to the control group (Group A). The second group (Group B) of rats received salicylate (Sigma Aldrich) intraperitoneally for 7 days (300 mg/Kg/day). The 3rd group (Group C) received salicylate intraperitoneally for 7 days, but at twice the concentration of the animals in the second group (600 mg/kg/d). The 4th group (Group D) simultaneously received salicylate (300 mg/Kg/day) and pure Memantine (Sigma Aldrich, 10 mg/kg/d) intraperitoneally for 7 days. The 5th group (Group E) did not receive any substance but was exposed for 168 consecutive hours (7 days) to sound to induce tinnitus. Cochlear activity was evaluated with the use of Distortion Product Otoacoustic Emissions (DPOAEs). At the end of the experimental period, the animals were sacrificed, and the right cochlea was removed and prepared for further histological and immunohistochemical studies. RESULTS: The DPOAEs of animals treated either with salicylate as monotherapy or salicylate combined with memantine were indistinguishable from the noise floor, did not differ significantly compared to the animals of the control group or those expose to constant noise. The cochlear structures of Group E remained anatomically and functionally unaffected from the exposure to constant noise. Memantine does not seem to offer substantial protection to the cochlear structures, according to histological examination and hearing tests, however, the rats receiving it exhibited better results in behavioral tests. CONCLUSIONS: The administration of memantine does not contribute significantly to the reduction of tinnitus.

Efficacy and safety of parenteral and local application of tramadol in mandibular third molar extraction: a qualitative systematic review of current evidence.

PURPOSE: To assess the efficacy and safety of perioperative parenteral administration or submucosal infiltration of tramadol for perioperative pain control on the basis of pain intensity or analgesics consumption and perioperative outcomes in mandibular third molar surgery. MATERIAL-METHODS: An electronic database search was conducted up to 10 November 2022 to retrieve all randomized controlled trials (RCTs), assessing the analgesic efficacy of parenteral use of tramadol implemented as an adjunct to local anesthesia or intraoperative sedation/general anesthesia, in surgical extraction of mandibular third molars. Modified Jadad scale and Cochrane bias tool were used for the qualitative appraisal. RESULTS: Nineteen RCTs were selected for qualitative analysis. Nine studies involved intravenous, and 5 intramuscular administration of tramadol, while 5 evaluated submucosal infiltration with tramadol. Intravenous or intramuscular tramadol provided a weaker analgesic effect compared with non-steroidal anti-inflammatory drugs (NSAIDs), while intravenous tramadol induced an enhanced analgesic effect than oral tramadol. Parenteral administration of tramadol improved the quality of postoperative analgesia versus placebo. No notable adverse effects were recorded. CONCLUSIONS: Parenteral or submucosal infiltration of tramadol constitutes an effective and safe alternative analgesic approach in surgical extraction of mandibular third molars, yet the nociceptive effect of this analgesic modality could not supersede that of NSAIDs. TRIAL REGISTRATION: PROSPERO No CRD42021227574.

The inhibitory effect of tocilizumab on systemic bone loss and tendon inflammation in a juvenile Collagen-Induced arthritis rat model.

PURPOSE OF THE STUDY: Reduced Bone Mineral Density (BMD) is a prevalent comorbidity in Juvenile Idiopathic Arthritis (JIA). Enthesitis and other tendon abnormalities, such as tenosynovitis, tendinitis and tendon ruptures are, also, common extra-articular manifestations of the disease. The aim of the present study was to investigate the effect of tocilizumab, an antibody that binds the Interleukin-6 (IL-6) Receptor, on inflammation-related bone loss and tendon inflammation in an animal model of JIA. MATERIALS AND METHODS: The Collagen-Induced Arthritis (CIA) model was induced in male rats followed by intraperitoneal administration of tocilizumab for 8 weeks. Methotrexate, the most widely used Disease-Modifying Antirheumatic Drug in the management of JIA, was, also, administered, either as a monotherapy or as an add-on therapy to tocilizumab. BMD was evaluated with Micro-Computed Tomography (Micro-CT) and histopathological examination. Tendon damage was, also, assessed histologically. Finally, two pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-23 (IL-23) were quantified in tendon tissues by ELISA analysis. RESULTS: Tocilizumab-treated animals exhibited a significantly improved trabecular microarchitecture on micro-CT analysis and histological examination. Tendon morphology was also improved. Anti-IL-6 treatment led to a significant decrease in TNF-a and IL-23 expression in tendon tissue. CONCLUSIONS: The results of the present study provide evidence that tocilizumab reduces inflammation-related bone loss and suppresses tendon inflammation in a juvenile CIA rat model. These findings offer perspectives for the management of osteoporosis and enthesitis in JIA.

Prevalence of post-menopausal depression and associated factors: A web-based cross-sectional study in Greece.

OBJECTIVES: The impact of depression on post-menopausal women is an important public health issue but remains largely unknown. The purpose of this study was to identify the prevalence of post-menopausal depression in Greece and outline the profile of the women it affects. STUDY DESIGN: A sample of post-menopausal women completed an anonymous, self-administered, web-based survey which included the Beck Depression Inventory-ΙΙ (BDI-II) and questions regarding socio-demographic data. MAIN OUTCOME MEASURES: The dependent variable of interest was a BDI-II score ≥ 20 (the cut-off for moderate depression according to the BDI). RESULTS: Overall, 502 post-menopausal women participated in the study. The median BDI-II score was 13 (range 0-50); 136 (27.1%) of the women scored ≥ 20 and were considered screen-positive for depression. According to the multivariate logistic regression model, age< 55 years (OR: 1.621; 95% CI: 1.036-2.535), not working (OR: 1.580; 95% CI: 1.013-2.465), smoking (OR: 1.656; 95% CI: 1.081-2.536) and history of depression (OR: 1.650; 95% CI: 1.045-2.604) were independently associated with post-menopausal depression. Subgroup analyses revealed that current smokers (OR: 2.514; 95% CI: 1.485-4.256) had higher odds of moderate depression, while obesity (OR: 2.455; 95% CI: 1.206-4.996), absence of healthcare insurance (OR: 4.413; 95% CI: 1.970-9.887) and a history of depression (OR: 2.253; 95% CI: 1.212-4.190) were identified as independent risk factors for severe post-menopausal depression. CONCLUSIONS: More than one out of four post-menopausal women were screen-positive for symptoms indicative of depression, while a personal history of depression, age < 55 years, smoking and current working status were independent predictors of its emergence.

Effects of long-term infliximab and tocilizumab treatment on anxiety-like behavior and cognitive function in naive rats.

BACKGROUND: Circulating cytokines have been proposed to be implicated in the development of mood disorders and cognitive impairment. This study aims to examine the effect of chronic treatment with infliximab, a tumor necrosis factor-alpha (TNF-alpha) inhibitor, and tocilizumab, an antibody against interleukin-6 (IL-6) receptor on anxiety-like behavior and cognitive function. METHODS: Twenty-eight male, Wistar rats were randomly allocated into negative control, vehicle, infliximab and tocilizumab groups. After 8 weeks of intraperitoneal drug administration, rats performed the elevated-plus maze, the elevated-zero maze, the olfactory social memory and the passive avoidance tests. Brain sections at the level of the hippocampus, the amygdala and the prefrontal cortex were histologically examined. Finally, hippocampal and amygdaloid brain-derived neurotrophic factor (BDNF) expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Infliximab group exhibited a significantly higher number of entries and time spent into the open arms of the mazes, showing a lower level of anxiety. In the olfactory social memory test, tocilizumab significantly increased the ratio of interaction. Both infliximab- and tocilizumab-treated animals had a significantly lower latency time in the passive avoidance test that suggests an improved memory. Histological examination revealed similar morphology and neuronal density between groups. BDNF expression levels were significantly increased in the groups receiving anti-cytokine treatment. CONCLUSIONS: Our findings suggest that long-term peripheral TNF-alpha and IL-6 inhibition improves anxiety and cognitive function in rats and leads to an increased BDNF expression in the brain.

Infliximab and tocilizumab reduce anxiety-like behavior, improve cognitive performance and reverse neuropathological alterations in juvenile rats with severe autoimmune arthritis.

Several studies have demonstrated that rheumatic diseases, including Juvenile Idiopathic Arthritis (JIA), are associated with anxiety-like behavior and a cognitive decline. Infliximab, a Tumor Necrosis Factor-alpha (TNF-a) inhibitor, and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, are commonly used in the treatment of JIA. Here, we aimed to evaluate the effects of infliximab and tocilizumab on anxiety symptoms and cognitive function in a juvenile model of severe autoimmune arthritis. We found that both infliximab and tocilizumab improved anxiety-like behavior in the elevated-plus and elevated-zero maze tests. Tocilizumab, also, improved cognitive performance in the passive avoidance and olfactory social memory tests. Histological examination showed that anti-cytokine treatment reversed the histopathological alterations in the brain induced by arthritis. Further, infliximab and tocilizumab treatment increased Brain-Derived Neurotrophic Factor (BDNF) expression in the hippocampal and amygdaloid area of rat brain. In summary, our findings provide evidence that infliximab and tocilizumab have a beneficial effect on anxiety-like behavior and cognitive function and alleviate neuropathological alterations in a juvenile rat model of severe arthritis, suggesting that inhibition of TNF-a and IL-6 in the periphery, may be associated with a mood and memory enhancement in JIA patients.

Effects of Long-Term Methotrexate, Infliximab, and Tocilizumab Administration on Bone Microarchitecture and Tendon Morphology in Healthy Wistar Rats.

Objective Rheumatic diseases are associated with bone loss, both systemic and periarticular, and tendon abnormalities. The aim of this study is to examine the effect of three antiarthritic drugs, methotrexate, an anti-folate metabolite; infliximab, a Tumor Necrosis Factor-alpha (TNF-α) inhibitor; and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, on bone microarchitecture and tendon morphology in the absence of an inflammatory state. Materials and methods Thirty-five, 8- to 9-week-old, male, Wistar rats were randomly allocated into five groups: negative control (CTRL), vehicle (VEH), methotrexate (MTX), infliximab (INFX), and tocilizumab (TCZ). After 8 weeks of antiarthritic drug intraperitoneal administration, animals were euthanized and rat tibiae and patellar tendons were histologically examined. Results All sections exhibited normal bone microarchitecture. Histological scores in all groups corresponded to normal bone mineral density. No no apparent differences in tenocyte morphology and architecture of collagen fibers were observed. Conclusions The results of this study indicate that long-term administration of methotrexate, infliximab, and tocilizumab had no effect on bone microarchitecture and tendon morphology in rats in the absence of an inflammatory condition.

Exposure to the drug company marketing in Greece: Interactions and attitudes in a non-regulated environment for medical students.

BACKGROUND: Medical students are targeted by the pharmaceutical industry and are exposed to their marketing strategies even in the preclinical years of study. The marketing strategies used by pharmaceutical companies with physicians are also applied to students, affecting their future prescribing behaviour, and include low-cost non-educational gifts, travel expenses and conferences registration fees. In Greece, there are no national or institutional regulations and guidelines concerning drug company-medical student interactions. This study is the first time this estimate has been made in Greece and assessed a) the interactions between pharmaceutical companies and medical students, and b) students' attitudes towards pharmaceutical marketing. METHODS: A sampling of undergraduate medical students completed an anonymous, self-administered, web-based survey. The first part of the survey investigated the interaction between the students and pharmaceutical companies; the possible answers were the binomial variables 'yes' or 'no'. The second part assessed the students' opinions of pharmaceutical company marketing and the answer options were 'agree', 'don't know/don't answer' and 'disagree'. RESULTS: The survey was completed by 412 undergraduate medical students (mean age 22 ± 2.2 years, 52.7% were women); the overall response rate was 58.9%. Although the majority did not consider accepting gifts and meals from drug companies as ethical, most of them (59%) had accepted meals and low-cost non-educational gifts, especially the clinical-level students. Further, 52,6% of the students did not believe that accepting gifts from pharmaceutical companies would affect their own prescription behaviour, whereas surprisingly they held the opposite opinion of their classmates. The vast majority (85.9%) agreed that sponsored lectures were biased in favour of a company's products; however, 47.6% agreed that promotional material is useful for learning about new medications and 34.5% believed that medical schools should allow drug company representatives to interact with students. CONCLUSION: Our results suggest that medical students in Greece are notably exposed to pharmaceutical industry marketing and their conflicting answers demonstrate that they are inadequately prepared for this interaction. Interventions are needed so that students are prepared and able to manage these interactions critically.

Furosemide modifies heart hypertrophy and glycosaminoglycan myocardium content in a rat model of neurogenic hypertension.

Hypertension is a major risk factor for atherogenesis and heart hypertrophy, both of which are associated with specific morphological and functional changes of the myocardium. Glycosaminoglycans (GAGs) are complex molecules involved both in tissue morphology and function. In the present study, we investigated the effects of neurogenic hypertension and subsequent antihypertensive treatment with furosemide, on heart hypertrophy and the content of GAGs in the myocardium. Neurogenic hypertension was achieved in male Wistar rats by bilateral aortic denervation (bAD). At days 2, 7 and 15 after surgery, animals were sacrificed and the hearts were dissected away, weighted, and homogenized. Total GAGs were assessed by measuring the uronic acid content colorimetrically and individual GAGs were isolated and characterized by enzymatic treatment, with GAG-degrading enzymes, using electrophoresis on polyacrylamide gradient gels and cellulose acetate membranes. In bAD-animals blood pressure, blood pressure lability, heart rate and heart weight were significantly increased 15 days postoperatively. These effects were prevented by treatment with furosemide. Major GAGs identified in the heart were chondroitin sulphates, heparin (H), heparan sulphate (HS) and hyaluronic acid. The content of uronic and the relative content of H and HS in the heart in bAD animals significantly decreased from day 2 to day 15 postoperatively. Furosemide prevented the bAD induced decrease in GAG content. Considering that H and HS are potent inhibitors of cardiomyocyte hypertrophy, our results indicate that heart hypertrophy induced by neurogenic hypertension may be associated with decreases in the relative content of heparin and heparan sulphate in the heart.

Efficacy and safety of prophylactic levetiracetam in supratentorial brain tumour surgery: a systematic review and meta-analysis.

AIMS: The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients. METHOD: A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects. RESULTS: The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta-analysis. The combined results from the meta-analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03-0.42]: χ(2) = 1.76: I(2) = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14-2.99]: χ(2) = 8.79: I(2) = 77%). CONCLUSIONS: The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.

Memantine's action against aminoglycoside-induced ototoxicity.

The objectives of this study were (1) to assess the protective role of NMDA antagonists against the ototoxic effects of aminoglycosides, (2) to provide any possible evidence between ototoxicity due to aminoglycosides and excitotoxicity. An animal experiment was conducted. Twenty-eight, 3-month-old female New Zealand rabbits, weighing 1,000-1,500 g, were studied prospectively for 28 days after intramuscular administration of amikacin (15 mg/kg/day divided into two equal doses) for 14 days. Twenty-one rabbits were categorized into three equal treatment groups and seven animals received no medication and served as the control group. The animals of A, B and C groups were injected, intramuscularly, with amikacin 15 mg/kg/day, divided into two equal doses every day for 14 days. Animals of group A received in parallel memantine (per os) and those of group B received p.o. the same volume of placebo solution. The rabbits of the third group (group C) received on the 15th day and every 2 days for the next 2 weeks, until the day 28, memantine of the same quantity as the members of group A. Differences in DPOAE amplitudes, and therefore in cochlear activity, between group A and group B were revealed. DPOAE amplitudes of group B were further reduced compared to the respective amplitudes in rabbits of group A. No improvement was observed in DPOAE measurements performed after the discontinuation of injections. The findings in group C should be examined separately. The measurements showed apparent reversal ototoxic effects in four of the animals. The development of aminoglycoside otoprotective strategies is a primary goal in ototoxicity research. The administration of NMDA antagonists has been shown to prevent, at least to some extent, toxic damage to hair cells in guinea pigs, treated with aminoglycoside antibiotics.

Pregabalin abuse after past substance-seeking behavior.

Pregabalin is a prescription drug, structurally related to the neurotransmitter GABA. Following the rapidly increasing use of pregabalin, data signaling its abuse liability have been published recently. We report a case of a 19-year-old man with a history of cannabis and alcohol-seeking behavior that showed similar drug-seeking behavior with pregabalin. This report highlights the potential for abuse of pregabalin in patients with a history of substance-seeking behavior. Considering that the drug has recently been proposed as a treatment for alcohol- and benzodiazepine-dependence a better clarification of its abuse potential is essential.

An evidence-based review of risk-reductive strategies for osteonecrosis of the jaws among cancer patients.

PURPOSE: Bone antiresorptive treatment is associated with osteonecrosis of the jaws. Interventions used to treat this complication are diverse, controversial, and largely empirical but certain risk factors could help in its avoidance. The aim of this evidence-based review is to elucidate any interventions that are effective in reducing the risk for development of ONJ in cancer patients receiving bone antiresorptive therapy and to quantify the effectiveness of such interventions. MATERIALS & METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and other trial registries through January 2012. We selected randomized controlled trials (RCTs). Cohort studies were included only as long as there are no RCTs on the same modality. RESULTS: Twelve studies were included in the systematic review while nine studies contributed to the various comparisons. Prescribing denosumab (DSB) instead of zoledronic acid (ZA) may not be expected to reduce risk ONJ (RR:0.71 [99% CI: 0.41-1.24], I2=0%). Prescribing clodronate (RR:10.15 [99% CI: 2.43-42.35], I2=0%) or pamidronate (RR:4.41 [99% CI: 1.90-10.24], I2=16%) instead of ZA may reduce risk for ONJ. Dental extractions remain the most potent risk factor for ONJ (RR:14.04, [99% CI: 10.36-19.03], I2=0%) and their avoidance can be considered an effective risk-reductive intervention. ONJ risk can be reduced by dental prophylactic measures (RR:0.45, [99% CI: 0.23-0.85], I2=7%). CONCLUSIONS: DSB and ZA might cause ONJ more frequently compared with chlodornate or pamidronate. Prescription pamidronate and clodronate helps avoid the complication. Reducing the administered dose for denosumab and zoledronic acid might reduce risk for ONJ as well. More randomized clinical trials comparing reduced doses of these regimens against those currently approved are needed.

Effect of non-steroidal anti-inflammatory drugs on bone turnover: an evidence-based review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for acute and chronic pain control and treatment of inflammation, osteoarthritis and rheumatoid arthritis. NSAIDs have been shown to inhibit bone healing in animal studies due to the inhibition of prostaglandin synthesis. However, little evidence exists regarding the effect of NSAID exposure on human bone metabolism. This systematic review summarizes the current literature of randomized controlled trials (RCTs) investigating NSAIDs with bone remodeling-related outcomes in humans. After performing computerized searches in the most widely indexed databases, study selection, data abstraction and risk of bias assessment were conducted in duplicate. The results were controversial regarding the association of NSAID with bone formation or resorption. Increased bone mineral density following NSAID exposure was reported by some studies. Based on the levels of biochemical markers, no effect was seen on bone formation, while some evidence was found for a decreased rate of bone resorption in NSAID patients. Trials investigating the effects of NSAID treatment on bone metabolism outcomes of human patients are limited. Further research is required to confirm or refute the findings of this systematic review.

Evaluation of dietary habits and assessment of cardiovascular disease risk factors among Greek university students.

The aim of this study was the evaluation of dietary habits in regard to cardiovascular risk status in university students in Northern Greece. 215 students (101 males) (age 21.5±2.3 years) participated in the study. Dietary intake was determined by using 3-day food record (1 weekend day). Recorded energy and nutrient intakes were compared to RDA and recommendations given by the American Heart Association (AHA). Students' smoking status and familial chronic diseases were recorded. A percentage of 55.8% (males) and 45.7% (females) were physically moderately active. When compared to AHA guidelines, the students had averagely significantly higher intake of total fat, saturated fat, sodium and dietary cholesterol and lower intake of polyunsaturated fat, monounsaturated fat, folate, vitamin E and fiber. 95% of them failed to meet all AHA dietary recommendations, with polyunsaturated to saturated fat ratio and the percentage of total fat being the top two failed parameters and sodium (10.2%) being the one less problematic. Dietary habits of Greek university students differ from what is considered as health promoting and, in the case that it they are not altered, may have an adverse effect on their CV health, despite the fact that their mean body weight is only moderately high.

Eating habits, health attitudes and obesity indices among medical students in northern Greece.

Medical students represent not only the final but also the most crucial opportunity for education in the field of healthy lifestyles and nutritional habits. Eating habits and obesity indices among medical students in southern Greece were described almost a decade ago. However, there is a lack of current, relevant data concerning students living in northern Greece. The purpose of the present study was to evaluate the body mass index distribution and nutritional and health-related behavior among medical students in northern Greece. The participants, 187 males (21.5 ± 1.9 years) and 203 females (21.3 ± 2.2 years), filled out a self-report questionnaire. Height and weight measurements were obtained. Dietary practices of fast food consumption (more frequent for males) and regular consumption of fruits and vegetables (more frequent for females) were reported. Females seemed to adopt different practices than males when trying to lose weight and were significantly better informed about the nutrient value of the food consumed. Although the prevalence of overweight (males: 32.1%, females: 8.4%) and obesity (males: 5.9%, females: 1.5%) in the present sample is lower compared to previous data, it remains high according to what would be health promoting. The above findings suggest a need for further improvement in strategies promoting healthier nutrition habits.

Gabapentin for the treatment of hot flashes in women with natural or tamoxifen-induced menopause: a systematic review and meta-analysis.

BACKGROUND: Various nonhormonal agents have been used for the treatment of hot flashes in women with natural or tamoxifen-induced menopause. Some studies have reported that gabapentin appears to be an effective and well-tolerated treatment modality. OBJECTIVE: To investigate the efficacy and tolerability of gabapentin for the treatment of menopausal hot flashes, we performed a systematic review of all trials reporting on the efficacy and tolerability of gabapentin in women with hot flashes and a meta-analysis of the randomized controlled trials (RCTs) conducted in this patient population. METHODS: For the systematic review, a literature search was conducted through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for articles published in English from inception of the databases through November 2008. The reference sections of retrieved articles were searched, and a manual search of key journals and abstracts from major meetings in clinical pharmacology was conducted. To be included in the meta-analysis, RCTs had to compare gabapentin with placebo in the treatment of hot flashes in women with natural or tamoxifen-induced menopause, regardless of the sample size, dosage used, duration of treatment, or frequency of the episodes. Uncontrolled and openlabel trials were reviewed but excluded from the meta-analysis. The percent reduction in hot flash frequency (relative to baseline) and the composite score (summation of the number of hot flashes in each severity category multiplied by the severity score) were used as primary outcome measures. Dropout rates and the incidences of frequently reported adverse events (eg, dizziness/unsteadiness, fatigue/somnolence) were also investigated. RESULTS: The systematic review included 7 trials conducted in 901 patients between 2002 and 2008. Study sizes ranged from 22 to 420 patients, total daily doses of gabapentin ranged from 900 to 2400 mg, and titration periods lasted 3 to 12 days. All of the trials were conducted in North America (6 in the United States and 1 in Canada); 4 of the trials enrolled subjects with a history of breast cancer, whereas the remaining 3 trials only enrolled postmenopausal women. Four RCTs were included in the meta-analysis. Data were expressed as weighted mean difference (WMD) or relative risk (RR), with the associated 95% CI. Women assigned to gabapentin reported a significantly greater percent reduction in both the frequency of hot flashes (WMD = 23.72 [95% CI, 16.46-30.97]; P < 0.001) and the composite score (WMD = 27.26 [95% CI, 21.24-33.29]; P < 0.001), with significant between-study heterogeneity (I(2) = 97.8% and 95.6%, respectively). Dropouts due to adverse events were more frequent in women randomized to gabapentin than in controls (RR = 2.09 [95% CI, 1.13-3.85]; P = 0.02; I(2) = 0%). The risk of symptom clustering also was significantly higher in the treatment group than in the controls (dizziness/unsteadiness: RR = 6.94 [95% CI, 3.19-15.13]; P < 0.001; I(2) = 63.1%; and fatigue/somnolence: RR = 4.78 [95% CI, 2.23-10.25]; P < 0.001; I(2) = 0%). CONCLUSIONS: Comparisons of gabapentin and placebo revealed reductions of 20% to 30% in the frequency and severity of hot flashes with gabapentin, although data across the studies were too heterogeneous to provide a reliable summary effect. Clusterings of dizziness/unsteadiness and fatigue/somnolence were the most frequently reported adverse events associated with gabapentin and resulted in a higher dropout rate due to adverse events in the gabapentin-treated patients than in the controls. More studies are needed to consolidate the outcomes and elucidate useful details regarding this treatment.

Baroreceptors discharge due to bilateral aortic denervation evokes acute neuronal damage in rat brain.

Deep hypothermic circulatory arrest in cardiothoracic surgery evokes severe brain damages. On the other hand, blood pressure stimuli discontinuation to the brain has been found to induce alterations in neurotransmitter release, including glutamate, in numerous brain regions. Furthermore, it is well established that excessive glutamate release can induce neuronal injury, a process called excitotoxicity. Aim of the present study was the evaluation of possible acute neuronal damage after bilateral aortic denervation (bAD), imitating the baroreceptors discharge during circulatory arrest. Male, Wistar rats underwent either bAD or Sham operation under continuous hemodynamic monitoring. Two hours after completion of the procedure, rats were sacrificed and the brains were dissected and cut in specific levels corresponding to selective brain regions, based on either their participation in neuronal circuits, regulating blood pressure, or their vulnerability, after deep hypothermic circulatory arrest. Slices were stained and examined under light microscope using morphometric techniques. Increased number of necrotic neurons were found among bAD rats in amygdaloid complex (p=0.005), motor cortex (p=0.001), CA1 and CA3 (p=0.02 and 0.015) but not in posterior hypothalamic nucleus and Purkinje cell. Higher ratios of necrotic neurons were found in amygdaloid complex (p=0.002), motor layer (p=0.003 and p=0.000) and the hippocampal CA1 region (p=0.027) of bAD rats. The present study shows that baroreceptors discharge due to bAD may induce acute neuronal loss in brain regions involved in blood pressure regulation. Neuronal loss might be attributed to excitotoxic phenomena and it is following the same topographic distribution seen in deep hypothermic circulatory arrest, revealing a concurrent to hypoxia/ischemia mechanism of brain damage.