Comparison of the antinociceptive effect of acute morphine in female and male Sprague-Dawley rats using the long-lasting mu-antagonist methocinnamox

Male rats are more sensitive than female rats to the antinociceptive action of morphine. The present study used age-matched (9-10 weeks old) male and female Sprague-Dawley rats to investigate whether this difference is due to variation in mu-opioid receptor binding and G protein activation. In the warm-water tail-withdrawal assay at both 50 degrees C and 55 degrees C, morphine was 2-3 times more potent in males than females. In contrast, mu-opioid receptor number and the binding affinity of the mu-opioid agonists morphine and DAMGO in membranes from whole brain, cortex, thalamus, and spinal cord were not different between males and females. Similarly, morphine and DAMGO stimulation of G protein, determined using GTPase and [(35)S]GTPgammaS binding assays, did not show a difference between the sexes. The long-lasting mu-opioid receptor antagonist methocinnamox (0.32 mg/kg), given 24 h prior to morphine, reduced mu-opioid receptor number by approximately 50% in thalamic and spinal cord tissue from female and male rats and reduced the antinociceptive potency of morphine. Pretreatment of male rats with 0.32 mg/kg methocinnamox reduced the antinociceptive potency of morphine to that observed in female rats expressing a full complement of mu-opioid receptors. However, with increasing pretreatment doses of methocinnamox, the maximal antinociceptive effect of morphine was decreased in females but not males. The results suggest that pathways downstream of the mu-opioid receptor and G protein are more efficient in male rats than in female rats such that there is a larger receptor reserve for morphine-mediated antinociception.     

Differences in transplant-related complications between hematologic malignancies and solid tumors receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation

Multiple factors contribute to transplant-related complications after high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation, including conditioning regimens, number of infused stem cells and clinical characteristics of patient at transplant. We compared the transplant-related complications of 141 patients affected with hematological malignancies with those of 109 patients with solid tumors. The total number of peripheral blood stem cell transplantations performed was 339. High-dose chemotherapy mainly consisted of melphalan-, busulphan- or thiotepa-based regimens. Despite the equal number of infused CD34+ cells, patients with a hematological malignancy showed a slower absolute neutrophil count (days to neutrophils > 0.5 x 10(9)/L, 10.6 +/- 3.6 for hematological malignancies versus 9.1 +/- 1.2 for solid tumors, P < 0.0001) and platelet recovery (days to platelets > 20 x 10(9)/L, 16.4 +/- 9.8 for hematological malignancies versus 12.3 +/- 4.1 for solid tumors, P < 0.0001) than patients with a solid tumor. A significantly higher requirement of red blood cell (3.3 +/- 4.1 versus 2.0 +/- 1.9, P < 0.0029) and platelet units (7.5 +/- 10.4 versus 4.2 +/- 3.4, P < 0.0001) was observed for hematological malignancies than for solid tumors. Five graft failures were documented exclusively in patients with a hematological malignancy. Moreover, such patients displayed a longer duration of mucositis (P < 0.0028) and hospital stay (P < 0.0001), but no difference was observed in terms of febrile episodes. Transplant-related mortality was similar between the two groups. In conclusion, patients with a hematological malignancy overall have more complications than those with a solid tumor.     

Panax notoginseng (Burk.) effects on fibrinogen and lipid plasma level in rats fed on a high-fat diet

Several studies have shown that notoginsenoides improve diastolic function in hypertensive subjects, induce the fibrinolytic system in in vitro models and act as antiproliferative agents on vessel leiomyocytes. Our aim was to evaluate their effect on fibrinogen and lipid plasma levels compared with a well-known HMGCoA reductase inhibitor. Seventy Wistar male adult rats on a fat-enriched diet were treated orally with P. notoginseng pulverized root (43 mg/kg/day or 86 mg/kg/day; 20 animals per group), fluvastatin (3 mg/kg/day; 20 animals) or physiological saline (5 mL/kg/day; 10 animals). The ten rats on a normocaloric diet were also treated with 5 mL/kg/day of physiological saline. After a 28-day treatment, the rats were killed and their blood analysed with standard procedures. Treatment with 43 mg/kg/day of P. notoginseng or 3 mg/kg/day of fluvastatin showed similar activity in decreasing total cholesterol (-23.70%, -19.29%, respectively) and triglycerides (-21.59%, -18.55%). The most evident effect of P. notoginseng was the reduction of fibrinogenaemia in treated rats compared with the control values (-38.10%; p < 0.001), no dose-relationship being shown in this effect. Moreover, no significant variation in HDL cholesterol and glucose levels was observed nor did relevant behavioural changes occur in association with the root intake. Besides a moderate, non dose-related decrease in the plasma lipid levels, P. notoginseng appeared to induce a significant reduction in the rat fibrinogenaemia.     

Health profile of a population as a predictor of health resources utilization: results of the implementation of an epidemiologic model for needs analysis

The integration of the scientific researches in the assistance process is one of the most important challenges that is currently set to the health operators. In this paper a model for the health needs-assessment will be applied to verify if and how the prevalence of some classical risk factors for cardiovascular disease foretells mortality and hospitalisation episodes at 3 years, and if it could express the health need of that population. The "sanitary history" of 1704 subjects, enrolled in 1996 during the Brisighella Study, has been followed. We know the health profile of these subjects at 1996 and data about their hospitalizations, mortality, and general assistance from 1996 to 1999. In this population the risk of cardiovascular disease is inferior to that esteemed by the hospitalisation rate, attributable mostly to a little group of subjects with well-defined characteristics of exposure. The resources spent on a hospitalization do not adequately describe either the sanitary need nor the relief load and the "cost" associated to the disease. The methodology used allows to explore in detail the relative weight of the different subjects involved in the sanitary assistance in order to better reach the objective of producing the maximum quantity of benefits for the patient at the smallest possible quantity of risk.     

Double-blind controlled clinical study of the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel compared with diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel in patients with peri and extraarticular inflammatory diseases

To evaluate the efficacy and tolerability of the new diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel (DHEP lecithin gel, with 1.3% DHEP and 2.4% lecithin) compared with the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel (DHEP gel) in peri and extraarticular inflammatory states, a controlled, randomized, double-blind clinical study was conducted. Two groups of 50 patients each were enrolled and were given one of the two different formulations with a slight massage on the painful area three times a day for 10 consecutive days. Patients received a self-evaluation notebook in which to record daily assessment of spontaneous pain (Huskisson's visual analogue scale). On days 0, 3 and 10, the patients were visited by the investigator. All patients completed the study. The assessment of spontaneous pain showed that although pain decreased in both groups, the decrease was more marked in patients taking DEHP lecithin gel and that it reached a statistically significant difference at days 5, 6, 7 and 8. This decrease was also confirmed by assessments on the ordinal scale. Although periarticular swelling disappeared in both groups, swelling severity decreased sooner in patients taking DHEP lecithin gel. The efficacy and safety of both treatments was judged to be good or excellent by 70% of the patients in each group. The efficacy of the active principle, pyrrolidine salt, is confirmed. Moreover, the formulation containing lecithin passes through the skin lipid barrier more easily than the formulation without lecithin and is as valid as the other in the therapy of rheumatic disorders. Finally, DHEP lecithin gel preparation has a quicker therapeutic action on symptoms, such as spontaneous pain and local swelling, than DHEP gel.     

Expression of cadherins and CD44 isoforms in ovarian endometrial cysts

We evaluated the immunohistochemical expression of cadherins and CD44 variants in 20 endometriomas, 20 cystadenomas, 20 borderline ovarian tumours as well as 20 ovarian carcinomas, and the serological and cystic fluid concentrations of soluble E-cadherin and soluble CD44 standard (sCD44sdt) in 20 endometriomas, 20 cystadenomas, six borderline and 11 carcinomas of the ovary. In endometriomas, immunostaining of E- and N-cadherin was negative (20 and 30% respectively). CD44 H, v3 and v6 immunostaining were detected in 63, 10 and 40% respectively. A difference in immunostaining for E-cadherin was found between endometriomas and cystadenomas (P < 0.001) and for N- cadherin between endometriomas and carcinomas (P < 0.001). A difference in CD44H immunostaining was observed between endometriomas and cystadenomas (P < 0.035) but not with borderline ovarian tumours and carcinomas. No difference in serum concentrations of soluble E- cadherins and CD44 standard was found between the four groups of tumours. Cystic fluid concentrations of E-cadherin were lower in endometriomas than in borderline tumours and ovarian carcinomas (P < 0.001). High concentrations of soluble CD44 standard cystic fluid were found in endometriomas than in other ovarian cysts. Endometriomas and borderline tumours share alterations of cadherins and CD44 isoforms which may help in the understanding of the aggressive and invasive potentials of endometriotic cells.      

Combined lipoxygenase/cyclo-oxygenase inhibition in the elderly: the example of licofelone

One of the categories of drugs most frequently used by the elderly, and probably the most commonly self-prescribed class of drug in this age group, is NSAIDs. However, NSAIDs are one of the primary causes of adverse drug reactions and are notorious for their gastric toxicity. They also inhibit renal function and reduce the efficacy of diuretics and ACE inhibitors, drugs that are commonly used by elderly patients. Recent studies have shown that cyclo-oxygenase (COX)-2 is important in renal physiology. This means that selective COX-2 inhibitors, while undoubtedly safer than NSAIDs in terms of gastric toxicity, are not devoid of renal toxicity (in addition to their now clearly established adverse effects on coronary heart disease risk). Both the gastric and renal toxicities induced by traditional NSAIDs and selective COX-2 inhibitors seem to be related to inhibition of prostaglandin, but not leukotriene, synthesis. Maintaining the correct balance between prostaglandins and leukotrienes is essential for continuing good health, but both classes of mediators also play an important role in the pathogenesis of several diseases.Recently, a new class of anti-inflammatory drugs, the lipoxygenase (LOX)/COX inhibitors, has been developed as a means of simultaneously inhibiting the synthesis of prostaglandins, thromboxanes and leukotrienes. Inhibition of leukotriene synthesis increases anti-inflammatory efficacy, particularly in rheumatic diseases, while reducing the risk of gastric damage. The LOX/COX inhibitor licofelone, which is currently in phase III trials, is the first of this new class and in the most advanced stage of development. Preliminary data with this drug seem promising, but further well designed clinical trials of this agent in the elderly will be necessary before a final evaluation is possible.     

Matrix metalloproteinase-2, -9, and tissue inhibitor of metalloproteinase-1 in patients with hypertension.

There are conflicting data in the literature regarding the expression pattern of the vascular matrix metalloproteinase (MMP) system and their inhibitors (TIMPs) in human hypertension. The authors hypothesized that MMP-2, MMP-9, and TIMP-1 would be abnormal in hypertension, reflecting alterations in extracellular matrix (ECM) turnover. The authors measured plasma levels and activities of MMP-2, MMP-9, and TIMP-1 in 44 hypertensive patients and 44 controls. MMP-2 levels and activity were significantly higher in hypertensive group (p < .0001). Significant increase was also observed for MMP-9 level and activity (p < .0001) and for TIMP-1 (p < .0001) in hypertensive patients. Plasma levels and activities of MMP-2, MMP-9, and TIMP-1 are increased in hypertensive patients, which may reflect abnormal ECM metabolism.     

Metabolic effect of berberine–silymarin association: A meta‐analysis of randomized,double‐blind,placebo‐controlled clinical trials

The aim of this study is to assess the impact of a combination of berberine and silymarin on serum lipids and fasting plasma glucose (FPG) through a systematic review of literature and meta‐analysis of the available randomized, double‐blind, placebo‐controlled clinical trials (RCTs). A systematic literature search in SCOPUS, PubMed‐Medline, ISI Web of Science, and Google Scholar databases was conducted up to October 2, 2018, in order to identify RCTs assessing changes in plasma concentrations of total cholesterol (TC), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C) and FPG during treatment with berberine and silymarin in combination. Two review authors independently extracted data on study characteristics, methods, and outcomes. Quantitative data synthesis was performed using a random‐effects model. We identified five eligible RCTs, with 497 subjects overall included. Berberine and silymarin combination treatment exerted a positive effect on TC (mean difference [MD]: ?25.3, 95% CI [?39.2, ?11.4] mg/dl; p < 0.001), TG (MD: ?28, 95% CI [?35.3, ?20.6] mg/dl; p < 0.001), HDL‐C [MD: 6, 95% CI [3.2, 8.8] mg/dl; p < 0.001), LDL‐C (MD: ?29.1, 95% CI [?39.7, ?18.6] mg/dl; p < 0.001), and FPG (MD: ?7.5, 95% CI [?13, ?1.9] mg/dl; p = 0.008). The present findings suggest that the coadministration of berberine and silymarin is associated with an advantageous improvement in lipid and glucose profile, suggesting the possible use of this nutraceutical combination in order to promote the cardiometabolic health.