Dimitrios Kouvelas

Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis

What is known and Objectives:  Fibromyalgia (FBM) is a common chronic pain disorder affecting up to 2% of the general population. Current treatment options are mostly symptom‐based and limited both in efficacy and number. Two promising alternatives are gabapentin (GP) and pregabalin (PB). We aimed to estimate the efficacy and safety/tolerability of the two compounds in FBM through a systematic review and a meta‐analysis of relevant randomized double‐blind placebo‐controlled (RCT) were performed.

Effect of Early Compared With Delayed Enteral Nutrition on Endocrine Function in Patients With Traumatic Brain Injury An Open-Labeled Randomized Trial

BACKGROUND Traumatic brain injury (TBI) results in a hypermetabolic and hypercatabolic status in which adequate nutrition support is essential to improve clinical outcome. The endocrine system of a patient with TBI is also affected and may play a critical role in either the metabolic or the immunologic response to the trauma. In the present study, the effect of standard, delayed enteral feeding (DEF), compared with early (within 24-48 hours) enteral feeding (EEF), on the endocrine function of patients with TBI was investigated. METHODS This comparative, prospective, open-labeled, randomized study included TBI patients admitted to the intensive care unit (ICU). Injury severity was assessed by the Glasgow Coma Scale and predicted mortality by the Acute Physiology and Chronic Health Evaluation II. Twenty-five patients received DEF and 34 patients received EEF. The effect of the onset of nutrition on pituitary, thyroidal, gonadal, and adrenal function was investigated on days 6 and 12 after admission to the hospital. RESULTS Levels of thyroid-stimulating hormone, free triiodothyronine, free thyroxine, and testosterone (in males) of DEF patients declined in comparison to levels of the day of admission to the ICU. The decrease of hormonal values was less pronounced in the EEF group. Cortisol concentrations rose in the DEF group; a lesser hormonal change was found in the EEF group. Deaths during the study for the DEF group and EEF group were 2 and 3, respectively. CONCLUSIONS EEF may exert beneficial effects on the hormonal profile of TBI patients, possibly contributing to a better clinical outcome in this patient group.

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.

PDE5 Inhibitors: In Vitro and In Vivo Pharmacological Profile

PDE5 inhibitors have been clearly established as first-line therapy for the treatment of erectile dysfunction (ED). Three PDE5 inhibitors--sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis)--are currently approved by the FDA and the EMEA for use in ED, whereas sildenafil is also marketed under a different proprietary name (Revatio) for the treatment of pulmonary arterial hypertension (PAH). A forth PDE5 inhibitor, udenafil (Zydena), is currently marketed. In the present review the molecular basis and the mechanism of action of PDE5 inhibitors is discussed. In addition experimental and clinical data concerning their effects on different tissues, organs and systems is systematically reviewed and their possible beneficial action in numerous disorders is presented.

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.

Nandrolone abuse decreases anxiety and impairs memory in rats via central androgenic receptors

Anabolic androgenic steroids (AASs) affect areas of the central nervous system, which are involved in emotional and cognitive responses such as sexuality, anxiety, and memory. In the present study we imitated the abuse of AASs by administering high doses of the AAS nandrolone decanoate (ND) to rats. Thereafter rats were exposed to an elevated plus-maze and an olfactory social memory test to evaluate their anxiety-like and cognitive behaviour. To reveal whether these emotional and cognitive changes evoked by ND were caused via direct activation of androgenic receptors (ARs) in the brain, the AR antagonist flutamide (FL) was administered intracerebroventricularly (i.c.v.). Male rats were randomly divided in four groups, one group received 15 mg/kg ND subcutaneously, once daily for 6 wk (ND group). In the second group, in addition to ND, a daily dose of 5 microg FL was injected i.c.v. also for 6 wk (ND+FL group). The third group of rats received only FL and in the control group the vehicle was injected. The ND group clearly spent more time investigating the open arms in the maze test and recognizing the juvenile during the olfactory social memory test in comparison to the control group. In the ND+FL group rats showed similar emotional behaviour and cognitive ability to that of the control group. Injection of FL alone did not affect either anxiety or memory. These results indicate that repeated, high-dose administration of ND decreases anxiety and impairs memory in rats via direct activation of central ARs.

Topical tacrolimus and pimecrolimus in the treatment of cutaneous lupus erythematosus: an evidence-based evaluation.

BackgroundLesions of cutaneous lupus erythematosus (CLE) are refractory to a wide range of topical or systemic therapies. The pathogenesis of CLE is multifactorial and polygenic, and many of its details remain unclear. However, immunologic evidence suggests the possible therapeutic use of tacrolimus and pimecrolimus. CLE is one of the most common dermatological autoimmune disorders worldwide, which includes systemic lupus erythematosus (SLE) with malar rash, subacute cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE).ObjectiveOur aim was to determine the efficacy of topical pimecrolimus and tacrolimus in the treatment of cutaneous lupus erythematosus.MethodsThe literature was systematically reviewed. Medline, Embase, and the Cochrane Database were searched for systemic reviews, randomised controlled trials and nonrandomised clinical trials using the search terms “pimecrolimus”, “Elidel”, “SDZ ASM 981”, “tacrolimus”, “Protopic”, “FK506” and “cutaneous lupus erythematosus”. Studies were assessed independently by two authors.ResultsFive studies were eligible for inclusion in this review. Only one of them was a randomised controlled trial (RCT). There was no significant difference between tacrolimus and clobetasol; however, evidence indicates the highest tolerability of tacrolimus compared with corticosteroids. This review indicates the efficacy of tacrolimus and pimecrolimus in, at least initial, cutaneous lesions of SLE. However, in SCLE and DLE lesions, the efficacy appears to be lower, perhaps due to the chronicity of those lesions.ConclusionThe lack of RCTs is characteristic. Future studies should focus on efficacy, short- and long-term effects and cost-effectiveness. However, tacrolimus and pimecrolimus show efficacy, and such effort is worthwhile.

Release of glutamate and GABA in the amygdala of conscious rats by acute stress and baroreceptor activation: differences between SHR and WKY rats

To reveal the functional importance of amino acid neurotransmission in the amygdala (AMY) of conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, the in vivo release of glutamate (GLU) and GABA in this brain structure was studied using the push-pull superfusion technique. Basal GLU and GABA release rates in the AMY were comparable in SHR and WKY rats, although arterial blood pressure (BP) in SHR (152+/-6 mmHg) was higher than in WKY rats (102+/-4 mmHg). Neuronal depolarization by superfusion with veratridine enhanced the release of GLU and GABA to a similar extent in both rat strains. On the other hand, exposure to noise stress (95 dB) for 3 min led to a tetrodotoxin-sensitive increase in GLU release in the AMY of SHR, but not WKY rats. The concurrent pressor response to noise was enhanced in SHR as compared to WKY rats. A rise in BP induced by intravenous infusion of phenylephrine for 9 min had no effect on amino acid release in the AMY of both strains. The data suggest an exaggerated stress response of glutamatergic neurons in the AMY of SHR as compared with WKY rats, which might be of significance for the strain differences in the cardiovascular and behavioural responses to stress. The results also show that, in both rat strains, glutamatergic and GABAergic neurons in the AMY are not modulated by baroreceptor activation. Moreover, hypertension in adult SHR does not seem to be linked to a disturbed synaptic regulation of glutamatergic or GABAergic transmission in the AMY.

Efficacy, safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta-analysis.

Background  External anogenital warts (EGWs) are non‐malignant skin tumours caused by human papillomavirus. They are one of the fastest growing sexually transmitted diseases. Current treatments are unsatisfactory. Green tea sinecatechin Polyphenon E ointment is a botanical extract from green tea leaves exhibiting anti‐oxidant, anti‐viral and anti‐tumour properties.

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.