The Complex Role of Botulinum Toxin in Enhancing Goal Achievement for Post-Stroke Patients.

INTRODUCTION: The rehabilitation medical team is responsible for the therapeutic management of post-stroke patients and, therefore, for the complex therapeutic approach of spasticity. Considering the generous arsenal at our disposal in terms of both pharmacological treatment, through the possibility of administering botulinum toxin to combat spasticity, and in terms of accurate assessment through developed functional scales such as the GAS (Goal Attainment Scale), one of our purposes is to monitor the parameters that influence the achievement of functional goals set by patients together with the medical team in order to render the patients as close as possible to achieving their proposed functional goals, thus enhancing their quality of life. By assessing and establishing statistical and clinical correlations between the GAS and quantifiable parameters related to the affected post-stroke upper limb, namely degree of spasticity, motor control, pain level and evolution of pain under treatment with BoNT-A (abobotulinum toxin A), and patients' overall response to BoNT-A treatment, we aim to quantify the improvement of the therapeutic management of post-stroke patients with spasticity and develop a more personalized and effective approach to their disability and impairment. RESULTS AND DISCUSSIONS: The analysis concluded that there were two independent predictors of the Achieved GAS-T score (the study's endpoint parameter) motor control at any level of the upper limb and number of prior BoNT-A injections. The number of prior BoNT-A injections was an independent predictor of Achieved GAS-T score improvement but had no significant influence over Baseline GAS-T score. Enhancement in proximal and intermediate motor control showed a GAS score improvement of 3.3 points and a 0.93-point GAS score improvement for wrist motor control progress. From a separate viewpoint, patients with motor deficit on the left side have shown significantly greater improvement in Changed GAS-T scores by 2.5 points compared to patients with deficits on the right side; however, we note as a study limitation the fact that there was no statistical analysis over the dominant cerebral hemisphere of each patient. CONCLUSIONS: Improvement in the Achieved GAS-T score means better achievement of patients' goals. Thus, after the BoNT- A intervention, at follow-up evaluation, GAS was found to be directly correlated with improvement in motor control of the affected upper limb. Mobility of the corresponding limb was enhanced by pain decrease during p-ROM (passive range of motion) and by amelioration of spasticity. MATERIALS AND METHODS: We conducted an observational, non-randomized clinical study on 52 stroke patients, a representative sample of patients with post-stroke spasticity and disability from our neurological rehabilitation clinic, who have been treated and undergone a specific rehabilitation program in our tertiary diagnostic and treatment medical center, including BoNT-A focal treatment for spasticity in the affected upper limb. The primary objective of the study was to assess the influence of abobotulinum toxin A treatment on the Goal Attainment Scale. Secondary objectives of the study included the assessment of BoNT-A treatment efficacy on spasticity with the MAS (Modified Ashworth Scale), pain with the NRS (Numerical Rating Scale), and joint passive range of motion (p-ROM), identifying demographic, clinical, and pharmacological factors that influence the response to BoNT-A treatment, as well as to conduct a descriptive and exploratory analysis of the studied variables.

Immune profile of patients­a new approach in management of sepsis and septic shock?

The present study was a prospective observational single center study, enrolling 102 patients with sepsis, admitted in the Intensive Care Unit of the County Emergency Clinical Hospital in Târgu Mureș (Mureș, Romania). The main goal of the present study was to compare the changes of the following parameters on day 1 compared with day 5, in sepsis compared with septic shock, as well as in survivors compared with non-survivors: Cell blood count parameters, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and systemic inflammation index, C reactive protein (CRP), ferritin, procalcitonin (PCT), CD 3+ T cells, CD4+ T cells, CD8+ T cells, CD16+CD56+/CD3-NK cells and CD19+ B cells. The relationship between the subcategories of lymphocytes with the inflammatory markers was evaluated. The serum concentration of CRP and PCT was significantly lower on day 5 compared with day 1 and serum ferritin was significantly higher in patients with septic shock. The percentage of cytotoxic T lymphocytes was significantly decreased and the percentage of NK lymphocytes was significantly increased in patients who developed septic shock. The results indicated a negative significant correlation between the proportion of T lymphocytes and PCT concentration and a positive significant correlation between the proportion of B lymphocytes and PCT concentration.

Is Carboxyhaemoglobin an Effective Bedside Prognostic Tool for Sepsis and Septic Shock Patients?

Introduction: Proper management of sepsis poses a challenge even today, with early diagnosis and targeted treatment being the most important steps. Easy, cost-effective bedside tools are needed in order to pinpoint towards the outcome of sepsis or septic shock. Aim of study: This study aims to find a correlation between Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) severity scores, the Neutrophil-Lymphocytes Ratio (NLR) and carboxyhaemoglobin (COHb) levels in septic or septic shock patients with the scope of establishing a bed side cost-effective prognostic tool. Materials and methods: A pilot, prospective, observational, and ongoing study was conducted on 61 patients admitted with sepsis or septic shock according to the SEPSIS 3 Consensus definition. We followed clinical and paraclinical parameters on day 1 (D1) and day 5 (D5) after meeting the inclusion criteria. Results: On D1 we found a statistically significant positive correlation between each severity score (p <0.0001), r = 0.7287 for SOFA vs. APACHE II with CI: 0.5841-0.8285, r = 0.6862 for SOFA vs. SAPS II with CI: 0.5251-0.7998 and r = 0.8534 for APACHE II vs. SAPS II with CI: 0.7663 to 0.9097. On D5 we observed similar results: a significant positive correlation between each severity score (p <0.0001), with r = 0.7877 for SOFA vs. APACHE II with CI: 0.6283 to 0.8836, r = 0.8210 for SOFA vs. SAPS II with CI: 0.6822 to 0.9027 and r = 0.8880 for APACHE II vs. SAPS II., CI: 0.7952 to 0.9401. Nil correlation was found between the severity scores, NLR and COHb on D1 and D5. Conclusion: Cost-effective bedside tools to pinpoint towards the outcome of sepsis are yet to be found, however the positive correlation between the severity scores point out to a combination of such tools for prognosis prediction of septic or septic shock patients.

Roflumilast 0.3% Cream: a Phosphodiesterase 4 Inhibitor for the Treatment of Chronic Plaque Psoriasis.

BACKGROUND: Plaque psoriasis is a chronic dermatologic autoimmune disease that affects adults and children. Roflumilast 0.3% cream is currently the only topical phosphodiesterase 4 inhibitor indicated for the treatment of plaque psoriasis in patients 12 years or older. PHARMACODYNAMICS AND PHARMACOKINETICS: Roflumilast inhibits phosphodiesterase 4 inhibitor enzyme leading to the accumulation of cyclic adenosine monophosphate, which suppresses the inflammatory mediators interferon-γ and tumor necrosis factor-α. Roflumilast, applied once daily, reaches steady state by day 15 and has a half life of approximately 4 days in adults. Roflumilast undergoes extensive hepatic metabolism by cytochrome P450 enzymes and conjugation. Roflumilast is 99% bound to plasma proteins. CLINICAL TRIALS: Roflumilast efficacy and safety were evaluated in the DERMIS-1 and DERMIS-2 clinical trials. These identically designed, double-blind, vehicle-controlled phase 3 trials randomized 881 patients to roflumilast 0.3% cream or vehicle, applied once daily for 8 weeks. In DERMIS-1, the Investigator Global Assessment success rate was 42.4% with roflumilast 0.3% cream compared with 6.1% with the vehicle (32.3%-46.9%; P <0.001). Similarly, in DERMIS-2, the Investigator Global Assessment success rate was 37.5% with roflumilast 0.3% cream compared with 6.9% with the vehicle (20.8%-36.9%; P <0.001). Of 881 participants, 1% discontinued treatment with roflumilast cream due to adverse reactions compared with 1.3% treated with vehicle. Urticaria at the application site (0.3%) was the most common adverse reaction that led to discontinuation of roflumilast. THERAPEUTIC ADVANCE: To date, topical corticosteroids are the most commonly used agents to treat mild plaque psoriasis. Sensitive areas are often challenging to treat with existing topical therapy, including corticosteroids. Topical roflumilast has shown to be effective in treating sensitive areas, including skin folds, and may be an alternative to systemic therapy for some patients. The Food and Drug Administration approved topical roflumilast for the treatment of plaque psoriasis, including intertriginous areas, for patients 12 years or older.

Antidiabetic Molecule Efficacy in Patients with Type 2 Diabetes Mellitus-A Real-Life Clinical Practice Study.

In this paper, we aim to evaluate the efficacy of antidiabetic cardioprotective molecules such as Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) and Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs) when used with other glucose-lowering drugs, lipid-lowering, and blood pressure (BP)-lowering drugs in a real-life setting. A retrospective, observational study on 477 patients admitted consecutively in 2019 to the outpatient clinic of a tertiary care unit for Diabetes Mellitus was conducted. Body mass index (BMI), blood pressure (BP) (both systolic and diastolic), and metabolic parameters, as well as A1c hemoglobin, fasting glycaemia and lipid profile, including total cholesterol (C), HDL-C, LDL-C and triglycerides), were evaluated at baseline and two follow-up visits were scheduled (6 months and 12 months) in order to assess the antidiabetic medication efficacy. Both SGLT-2i and GLP-1 RAs were efficient in terms of weight control reflected by BMI; metabolic control suggested by fasting glycaemia and A1c; and the diastolic component of BP control when comparing the data from the 6 and 12-month visits to the baseline, and when comparing the 12-month visit to the 6-month visit. Moreover, when comparing SGLT-2i and GLP-1 RAs with metformin, there are efficacy data for SGLT-2i at baseline in terms of BMI, fasting glycaemia, and HbA1c. In this retrospective study, both classes of cardioprotective molecules, when used in conjunction with other glucose-lowering, antihypertensive, and lipid-lowering medications, appeared to be efficient in a real-life setting for the management of T2DM.

Studies Regarding the Antimicrobial Behavior of Clotrimazole and Limonene.

The paper presents the results of the studies performed to establish the effect of the mixtures between limonene and clotrimazole against microbial pathogens involved in dermatological diseases, such as Candida albicans, Staphyloccocus aureus, and Escherichia coli. Preliminary data obtained from the studies performed in microplates revealed a possible synergism between the mixture of clotrimazole and limonene for Staphylococcus aureus. Studies performed "in silico" with programs such as CLC Drug Discovery Workbench and MOLEGRO Virtual Docker, gave favorable scores for docking each compound on a specific binding site for each microorganism. The tests performed for validation, with the clotrimazole (0.1%) and different sources of limonene (1.9% citrus essential oils), showed a synergistic effect on Staphylococcus aureus in the case of the mixtures between clotrimazole and the essential oils of Citrus reticulata or Citrus paradisi. The studies performed on Staphylococcus aureus MRSA showed a synergistic effect between clotrimazole and the essential oils obtained from Citrus bergamia, Citrus aurantium, or Citrus paradisi. In the case of Pseudomonas aeruginosa, essential oils and clotrimazole used alone did not exhibit antimicrobial activities, but the mixtures between clotrimazole and the essential oils of Citrus bergamia or Citrus sinensis exhibited a synergistic antimicrobial effect.

Non-Insulin Novel Antidiabetic Drugs Mechanisms in the Pathogenesis of COVID-19.

The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease.

Survey on Anxiety and Post-Traumatic Stress Disorder in Intensive Care Personnel during the COVID-19 Pandemic in a Medically Under-Resourced Country.

The COVID-19 pandemic has increased the need for intensive care personnel. Romania has a low number of physicians per inhabitant. The stress of pandemics upon an already weak medical health system triggered some psychological effects upon burnt-out personnel. The main objective is to provide an insight into the psychological status of Romanian ICU personnel by evaluating their level of anxiety. The secondary objectives aim to identify the level of post-traumatic stress disorder and anxiety in different groups and to identify the personnel most affected psychologically. This study enrolled adult responders from the ICU of Târgu Mureș Emergency Clinical County Hospital, Romania, participating voluntarily. The evaluation tests were the State-Trait Anxiety Inventory and Post-Traumatic Stress Test. Out of the 126 eligible participants, 87 adult employees were enrolled-with a 69% response rate. The study comprised three groups: doctors, nurses, and auxiliary personnel. All three groups scored for moderate anxiety symptoms. COVID-19-related anxiety was strongly correlated with age and number of working years in all groups. Increased PTSD scores were observed in doctors and nurses. All ICU personnel who dealt with COVID-19 patients presented with moderate anxiety and post-traumatic stress disorder symptoms. The years of ICU experience had a positive impact on anxiety symptoms.

Anti-Psoriasis Effect of Diclofenac and Celecoxib Using the Tail Model for Psoriasis.

Non-steroidal anti-inflammatory drugs (NSAIDs) showed effects in some hyperproliferative dermatologic pathologies. The aim of the study is the assessment of anti-psoriasis effect of diclofenac and celecoxib using a mice tail model. The topical application of substances on the proximal mice tails was performed for two weeks. The effects on the epidermal granular layer and mean epidermal thickness (excluding the stratum corneum) were evaluated using hematoxylin-eosin staining. Orthokeratosis degree and percentual drug activity were calculated. A positive control group treated with tretinoin and two negative controls (white soft paraffin and untreated mice) were used. Orthokeratosis degree significantly increased in all the NSAIDs groups (celecoxib 1%, 2% and diclofenac 1%, 2%) and in the tretinoin 0.05% group, versus negative controls. Celecoxib 1% and 2%, tretinoin 0.05% and white soft paraffin significantly increased mean epidermal thickness, versus untreated mice. The values obtained in the case of celecoxib 2% ointment regarding the orthokeratosis degree and percentual drug activity are providing premises for further investigations regarding this effect and the mechanisms of action involved. Celecoxib 2% had the greatest percentual drug activity and is a promising substance for the anti-psoriasis topical treatment. Along with the COX-2 inhibition, celecoxib might have an anti-psoriasis effect by other independent mechanisms.

Endogenous Carboxyhemoglobin Level Variation in COVID-19 and Bacterial Sepsis: A Novel Approach?

BACKGROUND: The increased production of carbon monoxide (CO) in sepsis has been proven, but the blood level variations of carboxyhemoglobin (COHb) as a potential evolutionary parameter of COVID-19 and sepsis/septic shock have yet to be determined. This study aims to evaluate the serum level variation of COHb as a potential evolutionary parameter in COVID-19 critically ill patients and in bacterial sepsis. MATERIALS AND METHOD: A prospective and observational study was conducted on two groups of patients: the bacterial sepsis group (n = 52) and the COVID-19 group (n = 52). We followed paraclinical parameters on Day 1 (D1) and Day 5 (D5) of sepsis/ICU admission for COVID-19 patients. RESULTS: D1 of sepsis: statistically significant positive correlations between: COHb values and serum lactate (p = 0.024, r = 0.316), and total bilirubin (p = 0.01, r = 0.359). In D5 of sepsis: a statistically significant positive correlations between: COHb values and procalcitonin (PCT) (p = 0.038, r = 0.402), and total bilirubin (p = 0.023, r = 0.319). D1 of COVID-19 group: COHb levels were statistically significantly positively correlated with C-reactive protein CRP values (p = 0.003, r = 0.407) and with PCT values (p = 0.022, r = 0.324) and statistically significantly negatively correlated with serum lactate values (p = 0.038, r = -0.285). CONCLUSION: COHb variation could provide rapid information about the outcome of bacterial sepsis/septic shock, having the advantages of a favorable cost-effectiveness ratio, and availability as a point-of-care test.

The Effect of Topical Celecoxib as an Anti-Psoriasis Agent.

Our previous research showed that, in a mice tail model for psoriasis, topical celecoxib might have an antipsoriatic effect in vivo by increasing granular layer development. The aim of the present study is to assess the effect of three celecoxib concentrations using a mice model for psoriasis. Topical application of celecoxib (2%, 4% and 8%), with two negative controls (untreated and white soft paraffin as ointment base) and one positive control (tretinoin 0.05%), was performed for two weeks. The effect on granular layer development and epidermal thickness was measured on hematoxylin-eosin staining. The morphometric assessment was made by using mean orthokeratosis degree and mean epidermal thickness as main parameters. All celecoxib concentrations have significantly increased the mean orthokeratosis degree as a marker of an anti-psoriatic effect. Celecoxib 8% and 4% lead to a statistically significant increase in orthokeratosis degree when compared with celecoxib 2% and tretinoin 0.05%. Along with cyclo-oxygenase inhibition, other mechanisms of action of celecoxib are discussed. This study offers valuable information for future clinical trials with celecoxib as a topical anti-psoriasis agent.

Experimental research in topical psoriasis therapy (Review).

Psoriasis, one of the most prevalent inflammatory diseases in dermatologic pathology, remains a challenge in regards to the therapeutic approach. Topical therapy for psoriasis is a current trending subject as it implies good compliance for the patient, few adverse systemic reactions and a targeted effect. Numerous substances are now being tested, from natural to synthetic compounds and already known substances in improved formulas such as vesicular systems. The aim of this article was to conduct a literature review regarding the topical therapy of psoriasis in animal models, between June, 27, 2019 and July 9, 2020. For this article, the authors conducted extensive research in PubMed with the following keywords: Psoriasis AND (topical OR local) and (therapy OR treatment) AND (mice OR rats). The main new studied substances included lycopene, sodium butyrate, salvianolic acid B, small interfering RNAs (siRNAs) in ionic liquids, albendazole, phosphodiesterase inhibitors, biomimetic reconstituted high-density lipoprotein nanocarrier gel containing microRNA (miRNA)-210 antisense, thymoquinone in ethosomal vesicle, Sea buckthorn oil (Hippophae rhamnoides), nitidine chloride, Melissa officinalis spp. Altissima extract and [1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol (CIM). New formulas of already known anti-psoriasis substances such as: Cyclosporine, methotrexate, calcipotriol, tazarotene, protein kinase p38 and integrin α5ß1 as a target, are also reviewed. Recent research in topical psoriasis underlines the importance of animal experimental research in dermatology, providing a starting point for developing new therapeutic approaches in one of the most frequently diagnosed chronic dermatologic diseases. Vesicular systems are now providing the best vehicle for topical therapy, thus easing the action of the active substances at their target sites.

Association between Liver Cirrhosis and Diabetes Mellitus: A Review on Hepatic Outcomes.

BACKGROUND: Liver cirrhosis (LC) is largely associated with diabetes mellitus (DM). More than 80% of patients with LC manifest glucose intolerance and about 30% have type 2 DM. A particular and yet unrecognized entity is hepatogenous diabetes (HD), defined as impaired glucose regulation caused by altered liver function following LC. Numerous studies have shown that DM could negatively influence liver-related outcomes. AIM: We aimed to investigate whether patients with LC and DM are at higher risk for hepatic encephalopathy (HE), variceal hemorrhage (VH), infections and hepatocellular carcinoma (HCC). The impact of DM on liver transplant (LT) outcomes was also addressed. METHODS: Literature search was performed in PubMed, Ovid, and Elsevier databases. Population-based observational studies reporting liver outcomes in patients with LC were included. RESULTS: Diabetics are at higher risk for HE, including post-transjugular intrahepatic portosystemic shunt HE. DM also increases the risk of VH and contributes to elevated portal pressure and variceal re-bleeding, while uncontrolled DM is associated with increased risk of bacterial infections. DM also increases the risk of HCC and contributes to adverse LT outcomes. CONCLUSIONS: Patients with DM and LC may benefit from close follow-up in order to reduce readmissions and mortality. Due to the heterogeneity of available research, prospective multicenter clinical trials are needed to further validate these findings.

Antimicrobial peptides as an argument for the involvement of innate immunity in psoriasis (Review).

Antimicrobial peptides (AMPs) are a group of oligopeptides found in most multicellular organisms with a capacity for rapid and nonspecific destruction of pathogens. The action of destroying pathogens is associated with a strong proinflammatory activity, stimulating the secretion of cytokines, chemokines, growth factors but also chemotaxis, the activation of dendritic cells and involving adaptive immunity also. The action of AMPs fits perfectly into the characteristics of innate immunity which makes these peptides candidates to be considered as an important element of this type of immunity. It has been shown that AMPs are involved in a number of cellular processes such as: differentiation, proliferation, maturation, thus widening the degree of involvement of these peptides in the pathogenesis of chronic inflammatory diseases. In psoriasis, AMPs act both as a pro-inflammatory and chemotaxis factor and through the cathelicidin (LL-37)/dc DNA complex as a possible autoantigen for T cells, triggering an autoimmune response, activating the Th17/IL23 axis and maintaining the inflammatory process. Thus, many arguments are accumulated to consider that innate immunity through AMPs is an important link in the pathogenesis of psoriasis. Moreover, the action of antimicrobial peptides in psoriasis is almost entirely characteristic for the general mode of action of innate immunity.

The Diagnostic and Prognostic Role of Vascular Endothelial Growth Factor C in Sepsis and Septic Shock.

INTRODUCTION: Variations in the expression of vascular endothelial growth factor (VEGF) could be used as a biomarker in critically ill patients with sepsis and septic shock. Inflammation potently upregulates VEGF-C expression via macrophages with an unpredictable response. This study aimed to assess one of the newer biomarkers (VEGF-C) in patients with sepsis or septic shock and its clinical value as a diagnostic and prognostic tool. MATERIAL AND METHODS: The study involved 142 persons divided into three groups. Group A consisted of fifty-eight patients with sepsis; Group B consisted of forty-nine patients diagnosed as having septic shock according to the Sepsis -3 criteria. A control group of thirty-five healthy volunteers comprised Group C. Severity scores, prognostic score and organ dysfunction score, were recorded at the time of enrolment in the study. The analysis included specificity and sensitivity of plasma VEGF-C for diagnosis of septic shock. Circulating plasma VEGF-C levels were correlated with the APACHE II, MODS and severity scores and mortality. RESULTS: The mean (SD) plasma VEGF-C levels in septic shock patients (1374(789) pg./m), on vasopressors at the time of admission to the ICU, were significantly higher 1374(789)pg./mL, compared the mean (SD) plasma VEGF-C levels in sepsis patients (934(468) pg./mL); (p = 0.0005, Student's t-test.) Plasma VEGF-C levels in groups A and B were shown to be significantly correlated with the APACHE II (r = 0.21, p = 0.02; r = 0.45, p = 0.0009) and MODS score (r = 0.29, p = 0.03; r = 0.4, p = 0.003). There was no association between plasma VEGF-C levels and mortality [p = 0.1]. The cut-off value for septic shock was 1010 pg./ml. CONCLUSIONS: VEGF-C may be used as a prognostic marker in sepsis and septic shock due to its correlation with APACHE II values and as an early marker to determine the likelihood of developing MODS. It could be used as an early biomarker for diagnosing patients with septic shock.

A Systematic Review of Clinical Studies on the Effect of Psychoactive Cannabinoids in Psychiatric Conditions in Alzheimer Dementia.

BACKGROUND: The systematic reviews and meta-analyses performed until now did not provide the adequate picture of actual knowledge in the field of neuropsychiatric symptoms treatment using psychotropic cannabinoids in patients with Alzheimer disease (AD). THE STUDY QUESTION: Which is the level of evidence, from quantitative and qualitative point of view, concerning the efficacy and safety of the treatment with psychotropic cannabinoids of neuropsychiatric symptoms in AD? STUDY DESIGN: PubMed, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar Data, and Clinicaltrials.gov were searched for randomized clinical trials with cannabinoids in Alzheimer dementia agitation and aggression. MEASURES AND OUTCOMES: The rationale, the objectives, and the methods used for searching the trials have been established according to PRISMA Criteria 2009. RESULTS: The total number of patients in the 9 publications evaluated in this study, which included data from 6 clinical trials, was 422 patients-treatments, where treatment was a psychoactive cannabinoid or placebo, some of them obtained by multiplying selected patients with the number of cannabinoid treatments in the crossover studies. There are multiple sources of bias in the analyzed studies; 2 elements have prevented conclusive results. One element was polypragmazia, a major role being played by the use of psychotropic drugs other than cannabinoids, in an effort to reduce agitation and aggressive behavior. The second one was the large number of concomitant symptoms, for example, pain (commonly causing anxiety and agitation). CONCLUSIONS: No clear conclusion can be drawn on the effectiveness of psychoactive cannabinoids in the treatment of psychiatric manifestations, in particular agitation and aggression, in AD. In the future, large randomized controlled trial with adequate designs, without crossover and for longer duration, adapted to cannabinoid pharmacokinetics, is required to establish the real efficacy and safety of these drugs in aggressive and/or agitated patients with AD.

Antidepressant effect of the interaction of fluoxetine with granisetron.

Selective serotonin reuptake inhibitors (SSRIs) may produce digestive side effects such as nausea and vomiting, diarrhoea and decreased appetite. These side effects are determined by the increase in serotonin availability at 5-HT3 receptors. Granisetron, a serotonin 5-HT3 receptor antagonist, is expected to antagonize the digestive adverse effects of serotonin reuptake inhibitors, but the question is to what extent granisetron influences the antidepressant effect of these substances. The aim of this study was to determine the dose of fluoxetine that has an antidepressant effect in the Porsolt test, and the interaction between fluoxetine and granisetron with respect to the antidepressant effect in this test. In experiment 1, fluoxetine was antidepressant only at 20 mg/kg body weight (bw). In experiment 2, granisetron 1 mg/kg bw had a statistically significant antidepressant effect vs. control. Fluoxetine 20 mg/kg bw associated with a small dose of granisetron (0.1 mg/kg bw) produced a significant antidepressant effect vs. control. This shows that low doses of granisetron associated to fluoxetine might produce a significant antidepressant effect, suggesting a potentiation between these two drugs used in sub-effective antidepressant doses. In conclusion, in our experimental conditions, we can assume that granisetron in low doses could be used to combat intestinal transit disorders produced by SSRI antidepressants. These low doses are preferred, because they increase the antidepressant effect of these SSRIs.

Dermatology facing autoinflammatory syndrome.

Cutaneous symptoms are characteristic for the autoinflammatory disorders (AIDs), both in the classical autoinflammatory phenotype and in most disorders included in this syndrome, but they are not specific and inconstant. Several skin disorders (pyoderma gangrenosum and pustular acne) may be encountered either isolate or associated with autoinflammatory symptoms, forming well-defined clinical entities within the autoinflammatory syndrome. The high prevalence of cutaneous manifestations is an important characteristic of AIDs. The presence of cutaneous symptoms in AIDs opens the perspective of understanding the contribution of innate immunity mechanisms involved in skin pathology. It is possible that many diseases present the alteration, in various degrees, of the innate immune mechanisms. Recently, dermatology faced two challenges connected to AIDs. The first involves the diagnosis of skin symptoms in a clinical autoinflammatory setting and the investigative approach to identify a disorder classified as AID. The second is to identify the altered mechanisms of inborn immunity among the pathogenetic mechanisms of known dermatological diseases (e.g., neutrophilic dermatoses). On the other hand, cutaneous symptoms are in certain cases regarded as a criterion to asses the efficacy of specific or non-specific therapies with monoclonal antibodies in disorders included in AIDs. Dermatology mostly benefits from the identification and knowledge of AIDs due to the role of innate immunity in skin pathogeny and also due to the large extent of clinical forms resulting from the association of skin symptoms with other disorders included in this group.

Correlation between corneal thickness and optic disc morphology in normal tension glaucoma using modern technical analysis.

The purpose of this study was to evaluate the relationship between central corneal thickness (CCT) and optic disc morphology in normal tension glaucoma (NTG). Patients with NTG underwent eye examination, optic disc imaging with Heildelberg Retina Tomograph II (HRT II) and ultrasound corneal pachymetry. The morphological parameters of the optic discs were used to classify the eyes into four groups: generalized enlargement (GE) type, myopic glaucomatous (MY) type, focal ischemic (FI) type and senile sclerotic (SS) type. A correlation between CCT and optic disc morphology obtained by HRT II was calculated. Multiple comparison and post hoc tests were performed in order to determine the significance of the differences between the four groups. The strongest correlation was between CCT and the parameters of optic disc imaging obtained at HRT II in the GE type of optic disc.

Axillary basal cell carcinoma--a rare form of a frequent kind of carcinoma.

Basal cell carcinoma (BCC) is the most common cutaneous cancer. It seems that the most important prognostic factor is exposure to ultraviolet radiation (solar and artificial), correlated with other factors as well. In this article, we aimed to review basal cell carcinoma located in the axilla, referring to cases from our hospital. Axillary location of BCC is rare, with a very low number of cases quoted in the literature, compared to the high prevalence of basal cell carcinoma in the general population. During a period of two years, we detected only four cases of axillary basal cell carcinoma out of a total number of 921 cases diagnosed as BCC. We were interested in identifying certain factors involved in causing BCC, post-excision clinical evolution, histological type and aggressiveness of axillary basal cell carcinoma. Therefore, we quantified objectively the tumor and stromal expression of some immunological markers like: metalloproteinases MMP1, 3, 11, Ber-EP4 and Ki67. Histological types of tumors investigated here belong to the category of non-aggressive BCC, namely as nodular and superficial, although Ki67 index is greater than the average reported in the literature for this type of tumor. MMPs exhibited increased expression in tumors and stromal compartments, especially at the tumor invasion front, and was not associated with tumor ulceration or surrounding tissue remodeling-related changes. Our results confirm the literature data concerning the involvement of MMPs in BCC progression, whatever the tumor location is.