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1.

Introduction

Dental caries is the most prevalent disease in humans and its incidence is particularly high during childhood. The use of medicinal plants is a common practice in Brazil.

Objective

To evaluate the optimal antimicrobial concentration of Copaifera langsdorffii (copaiba) oil-resin, in the form of dental varnish, against Streptococcus mutans (S. mutans) in children.

Methods

Twenty-four children, caries-free, aged until 6?years old, were selected to participate in this study. The varnish was applied to the occlusal surfaces of all deciduous molars. The antimicrobial activity was analyzed in saliva, whose collection was conducted in two phases: before applying the copaiba varnish and after use to verify the instantaneous effectiveness of Copaifera langsdorffii dental varnish in the reduction of S. mutans. The microbiological analysis was repeated twice, establishing dilutions of 1:10?mL and 1:100?mL.

Results

Comparisons between different times within the same dilution were carried out by repeated measures analysis of variance (ANOVA) associated with Tukey’s multiple comparisons test. Comparisons of conditions prior to and after treatment were performed using the t test for paired samples and it indicated that the 1% formulation promoted a more significant decrease in the number of S. mutans colonies (p?=?0,0026).

Conclusion

Copaiba oil-resin, in the form of dental varnish, has antimicrobial activity against S. mutans in all the concentrations studied. Further studies to identify the long-term activity and anticaries effect of this varnish are required to establish its use in caries prevention.  相似文献   

2.

Background

Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of liver disease worldwide. There is growing evidence on pathogenesis and pathophysiology of NAFLD. However, there is still no universally accepted pharmacotherapy protocol.

Methods

The study was conducted on 42 patients with NAFLD. They were randomized to dietary treatment alone (n?=?21) or to diet and metformin therapy (n?=?21). Liver ultrasonography, controlled attenuation parameter (CAP), liver stiffness (LS), complete blood count, anthropometric and biochemical parameters were obtained before treatment (baseline), and after 3 and 5 months of the therapy.

Results

Patients treated with diet and metformin exhibited significantly decreased CAP values at 3 and 5 months of the therapy compared to baseline (319?dB/m vs. 285?dB/m; p < 0.05; 319?dB/m vs. 295?dB/m; p < 0.05 respectively). Five months of diet and the metformin therapy resulted in significant reduction of LS value (6.2?kPa vs. 5.2?kPa; p?<? 0.05), while patients treated with diet alone had no significant changes in liver CAP and LS measurements.

Conclusions

Metformin therapy combined with dietary treatment seems to be effective for the reduction of hepatic steatosis and fibrosis. However, considering limitations of the study and inconsistent results of previous investigations in this area, there is a need for further research on metformin efficacy in this group of patients.  相似文献   

3.

Background

Diabetes self-management (DSM) is a key element in the overall management of type-2 diabetes (T2DM). Identifying barriers and facilitators to DSM and addressing them is a critical step in achieving improved health outcomes in this population.

Objective

To assess patient reported barriers and facilitators to self-management of T2DM in a primary care setting.

Methods

This cross sectional study combined patient survey data with electronic medical record (EMR) data. Patients (age≥18 years) with a recorded diagnosis of T2DM (ICD-9 code: 250. xx) and having ≥2 physician visits were identified from a physician group's EMR database. Patients were grouped based on their A1C levels: <7, 7–9, and >9. Information on demographics, knowledge of diabetes, attitudes, health beliefs, and level of self-management was collected through survey administration. Survey responses were linked to the EMR data, and additional patient information was extracted.

Results

A total of 2100 surveys were administered (700 in each A1C category) of which 210 responses were received (10% response rate). Mean age was 63.7 years ( ±11.79), 108 (51.4%) were males, and 197 (93.8%) were Caucasian. Age (X2?=?15.73, p?<?0.01), insurance status (X2?=?12.03, p?<?0.05), referral to an endocrinologist (X2?=?6.17, p?<?0.05), level of self-management (X2?=?12.01, p?<?0.05) and willingness to use insulin (X2?=?9.8, p?<?0.01) were associated with glycemic variability. Level of self-management (X2?=?33.04, p?<?0.01) and referral to an endocrinologist (X2?=?11.11, p?<?0.01) were associated with readiness to change DSM behavior. Better self-management, older age, lower willingness to use insulin, and ‘less than graduate level’ education were significant predictors of glycemic stability.

Conclusions

Self-management behavior of patients with T2DM is strongly associated with glycemic stability. Interventions directed towards improving self-management in this population may result in improved clinical outcomes.  相似文献   

4.

Background

Drug-induced ototoxicity is still a main clinical problem in otolaryngology. It is widely known that aminoglycoside antibiotics combined with loop diuretics significantly contribute to permanent ototoxicity. The aim of this study was to find out whether ascorbic acid (vitamin C) is able to reverse or alleviate ototoxicity evoked by systemic (ip) administration of combination of amikacin and furosemide in experimental male albino Swiss mice.

Methods

Ototoxic combination of amikacin and furosemide was isobolographically evaluated based on the hearing threshold decreasing doses by 20% and 50% (TDD20 and TDD50), respectively. Linear regression analysis was used to determine the TDD20 and TDD50 values for amikacin, furosemide, vitamin C administered alone and in combination (at the fixed-ratio of 1:1).

Results

Vitamin C (in a dose of 500?mg/kg, ip) alleviated the impairment in hearing threshold evoked by combined ip administration of amikacin and furosemide (at the fixed-ratio of 1:1) in mice by reducing TDD50 values from 49.82 to 21.56 (p?<? 0.01). In contrast, vitamin C (500?mg/kg, ip) had no significant effect on TDD20 values for the combination of amikacin and furosemide at the fixed-ratio of 1:1.

Conclusions

Vitamin C administered together with ototoxic drug combination of amikacin and furosemide reduced ototoxicity evoked by this two-drug combination in the experimental mice.  相似文献   

5.
6.

Background

Food allergy (FA) is a worldwide health problem, affecting nearly 10% of all populations, with no prophylactic options or regulatory treatment available until now. Fisetin, a biologically active flavonoid, and telmisartan, the highly selective competitive AT1 receptor antagonist, recently exhibited potent anti-inflammatory and immunomodulatory activities. In the present study, we have evaluated the possible anti-inflammatory and immunomodulatory activities of fisetin and telmisartan each alone or in low-dose combination in a mouse model of FA.

Methods

For induction of FA, eight-week-old BALB/c mice, sensitized by two ip injection of 50 μg ovalbumin (OVA) and 1?mg alum at day 0 and 7. Then, each mouse challenged with 10 mg OVA at days 14, 16, 18, and 21. On the 28th day, the fifth challenge carried out by oral administration of 50?mg OVA. Either fisetin (1 or 3?mg/kg/d), telmisartan (1 or 3?mg/kg/d) or a combination of fisetin 1?mg/kg/d and telmisartan 1?mg/kg/d received orally from the 13th day till 28th day. In challenge days, the treatments received one-hour before the challenge.

Results

Our data showed that fisetin and telmisartan each alone or in low-dose combination attenuated the anaphylactic manifestation, decreased blood eosinophilic count, serum OVA-specific IgE, and IL-4 levels, the intestinal total and degranulated mast cells count, and CD4+ immunohistochemical expression. Furthermore, they enhanced the serum IFN-γ level and abrogated the intestinal histopathological changes induced by OVA in mice.

Conclusion

Either fisetin, telmisartan or their low-dose combination could be promising in the management of FA.  相似文献   

7.

Background

Multidose drug dispensing (MDD) is used to help patients take their medicines appropriately. Little is known about drug regimen changes within these MDD systems and how they are effectuated by the community pharmacist. Manual immediate adjustments of the MDD system could introduce dispensing errors. MDD guidelines therefore recommend to effectuate drug regimen changes at the start of a new MDD system.

Objective

The aim of this study was to investigate the frequency, type, procedure followed, immediate necessity, and time taken to make MDD adjustments.

Methods

This was a cross-sectional study in eight community pharmacies in the Netherlands. All adjustments to MDD systems were systematically documented for 3 weeks by the community pharmacist.

Results

Overall, 261 MDD adjustments involving 364 drug changes were documented for 250 patients: 127 (35%) drug changes involved the addition of a new drug, 124 (34%) a change in dosage, and 95 (26%) drug discontinuation. Of the MDD adjustments, 135 (52%) were effectuated immediately: 81 (31%) by adjusting the MDD system manually, 49 (19%) by temporarily dispensing the drug separately from the MDD system, and 5 (2%) by ordering a new MDD system. Pharmacists considered that 36 (27%) of the immediate MDD adjustments could have been deferred until the next MDD system was produced. Immediate adjustment took significantly longer than deferred adjustment (p?<?0.001).

Conclusions

This study shows that in patients using MDD systems, over half of the drug regimen changes are adjusted immediately. The necessity of these immediate changes should be critically evaluated.  相似文献   

8.

Background

Due to anti-inflammatory and anti-thrombotic functions, statins and antiplatelets are widely used for patients with cardiovascular-related or coronary artery diseases. Patients with systemic or complex diseases are commonly prescribed multiple targeted medications; thus, a proper combination of two or more drugs for beneficial efficacy is considered in clinical therapy. Recent studies have suggested that combinational therapy with statins and other medications accelerates their single effect to suppress inflammatory responses. However, the therapeutic efficacy and underlying mechanism of combination treatment with rosuvastatin and cilostazol have been poorly studied.

Methods

Mice were administered rosuvastatin alone, cilostazol alone or rosuvastatin and cilostazol in combination, and then injected with LPS or TNF to induce acute inflammation. The serum TNF level, macrophage infiltration of the lesioned aortas and mice mortality were observed in the acute inflammation model. The phosphorylation of MAPK was analyzed in TNF-stimulated HeLa cells.

Results

Compared to the treatment with cilostazol alone, the combination treatment with rosuvastatin and cilostazol significantly reduced not only the levels of TNF in the sera but also macrophage infiltration in aortic lesions. In addition, the combination therapy decreased TNF-mediated phosphorylation of the MAPK signaling pathway and improved the survival rate in the TNF-driven inflammatory mice model.

Conclusion

Rosuvastatin combined with cilostazol therapy can greatly improve the anti-inflammatory effect of monotherapies, resulting in reduced mortality of mice; thus, we propose the potential of use of this combination therapy as anti-TNF agent.  相似文献   

9.
10.

Background

Individuals who suffer from major cardiovascular events every year have one or more risk factors. Cardiovascular disease (CVD) risk assessment is an important strategy for the early identification of modifiable risk factors and their management. There is substantial evidence that shifting the focus from treatment to primary prevention reduces the burden of CVD.

Objectives

To evaluate the preparedness of community pharmacists in Qatar for the provision of CVD risk assessment and management services; and to explore the pharmacists' views on the provision of these services.

Methods

A cross-sectional study using simulated-client methodology. Using standardized scenarios, community pharmacists were approached for consultation on two medicines (Aspirin® and Crestor®) used for managing specific CVD risk factors. Pharmacists' competency to assess CVD risk was the primary outcome evaluated. Scores for each outcome were obtained based on the number of predefined statements addressed during the consultation.

Results

The mean cumulative score for all the competency outcomes assessed was 11.7 (SD 3.7) out of a possible score of 31. There were no differences for the majority of the competencies tested between the two scenarios used. Significantly more pharmacists exposed to the Aspirin® scenario than to the Crestor® scenario addressed hypertension as one of the risk factors needed to assess CVD risk (22% versus 11%, p?=?0.03); whereas significantly more pharmacists in the Crestor® scenario compared to the Aspirin® scenario, addressed dyslipidemia as one of the risk factors needed to assess CVD risk (30% versus 7%, p?=?0.02). Significantly more pharmacists exposed to the Aspirin® scenario provided explanation about CVD risk than those exposed to the Crestor® scenario 36% versus 8%, p?<?0.01).

Conclusion

The results suggest that many community pharmacists in Qatar are not displaying competencies that are necessary for the provision of CVD prevention services.  相似文献   

11.

Background

Menopause is associated with increased oxidative stress and memory impairment. Based on the antioxidant property of ascorbic acid (AA), It’s effect on cognitive function, the serum level of the brain-derived neurotrophic factor (BDNF) and the activity of antioxidant enzymes within the brain in ovariectomized (OVX) mice was investigated.

Methods

AA (100, 300 and 500?mg/kg), was orally administrated per day in OVX mice for 30 days. Tactile learning and working memory were evaluated by the novel object recognition task and T-maze continuous alternation task, respectively. The levels of serum BDNF were measured and animals’ brains were analyzed for the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity.

Results

AA prevented from the deleterious effects of ovariectomy on learning memory (300 and 500?mg/kg) and working memory (100 and 500?mg/kg). The serum BDNF level was also increased in OVX animals treated with AA (100 and 500?mg/kg). Furthermore, AA (500?mg/kg) increased the SOD and GPx activity in the brain of OVX animals.

Conclusions

Collectively, the results of the present study suggest that AA might be an appropriate choice in loss or reduction of estradiol for the amelioration of cognitive impairment.  相似文献   

12.

Background

Diabetes mellitus is a deadly disorder in human which induce chronic complications. The streptozotocin (STZ)-induced diabetes in rat is the most common animal model of human diabetes. The present study investigated the effects of novel indolizine derivatives (1–16) on plasma blood glucose concentrations in STZ-diabetic rats.

Methods

In vitro experiments were performed on 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide free radicals, α-glucosidase enzyme and in vivo studies on normal, oral glucose loaded and STZ-induced diabetic rats.

Results

Among all synthetic derivatives, compound 12 showed good inhibitory profile against DPPH, superoxide free radicals and α-glucosidase enzyme with half maximal inhibitory concentration (IC50) values of 56.2, 33.5 and 26.5?μg/mL, respectively. The lethal dosage of indolizine derivatives was found to be above 1000?mg/kg body weight (b.w.). From the in vivo studies, it can be determined that the compound 12 depicted pronounced protective hypoglycemic effects in normal, glucose-loaded and STZ-induced diabetic rats with respect to the standard. Furthermore, 21 days of successive treatment with compound 12 in diabetic rats exhibited better recovery of body weight and considerable variations in biochemical parameters as that of the standard drug. Moreover, the histopathological section of pancreas and testes justifies the rehabilitation and regeneration of islets, acini and Sertoli cells in animals treated with compound 12.

Conclusion

Our data suggest that the indolizine derivatives can be a benchmarks for designing potent oral antidiabetic agents.  相似文献   

13.
14.

Background

The central amygdaloid nucleus (CeA) is involved in processing and descending regulation of pain. Amygdaloid mechanisms underlying pain processing and control are poorly known. Here we tested the hypothesis that perioperative CeA administration of tetrapentylammonium (TPA), a non-selective THIK-1 channel blocker and thereby inhibitor of microglia, attenuates development of chronic neuropathic pain and comorbid anxiety-like behavior.

Methods

Rats with a spared nerve injury (SNI) model of neuropathy or sham operation had a chronic cannula for drug microinjections into the CeA or a control injection site. Monofilament test was used to evaluate pain, and light-dark box (LDB) to assess anxiety.

Results

Perioperative CeA treatment with TPA (30?μg/day up to the third postoperative day, D3) significantly attenuated the development of pain and anxiety-like behavior. In the late phase (> D14), CeA administration of TPA (3–30?μg) failed to influence pain. Perioperative minocycline (microglia inhibitor; 25?μg), MK-801 (an N-Methyl-D-aspartate receptor antagonist; 0.1?μg), vehicle or TPA in a control injection site failed to attenuate pain development.

Conclusions

Perioperative treatment of the CeA with TPA delayed development of neuropathic pain and comorbid anxiety-like behavior, while TPA treatment failed to influence maintenance of established neuropathic pain. The failures to attenuate pain development with CeA administrations of minocycline or MK-801 do not support the hypothesis that the TPA-induced prophylactic effect was due to inhibition of amygdaloid microglia or N-methyl-D-aspartate receptors. While TPA in the CeA proved to have a prophylactic effect on SNI-induced pain behavior, the underlying mechanism still remains to be studied.  相似文献   

15.

Background

Origin, synthesis and activity of quinaldic acid (QA), proposed derivative of kynurenic acid, have been poorly studied to date. Previously, we have demonstrated the antiproliferative effect of QA in a colon cancer model in vitro. The goal of present study was to verify QA activity to modify the expression of p53 tumor suppressor in colon cancer cells, and to relate it to its cancer cell growth inhibiting activity in vitro.

Methods

LS180 colon cancer cells possessing the wild type form of p53 were used in the study. Real-time PCR and immunobloting techniques were used to test the expression of p53 at gene and protein level, respectively. Next, immunocytochemistry was used to visualize the localization of p53 protein within the cells. Furthermore, the antiproliferative activity of QA was retested in cells with siRNA silenced P53 gene.

Results

The activity of QA to modify both the expression and phosphorylation of p53 protein as well as the level of P53 gene is shown. Concomitantly, the nuclear and cytoplasmic localization of phospho-p53 protein upon QA treatment is also presented. Moreover, reduced activity of QA in colon cancer cells with silenced p53 expression is observed.

Conclusion

QA affects the expression of p53 tumor suppressor, both at gene and protein level. The prominent contribution of p53 to the antiproliferative effect of QA in LS180 colon cancer cells can be suggested.  相似文献   

16.

Background

Sodium dichloroacetate (DCA) is an agent with anticancer properties against solid tumors. DCA also seems to have antileukemic activity. In order to affirm it we investigate the effect of DCA on cell viability and apoptotic gene expression profiles in leukemia cell lines: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2.

Methods

Cell viability was assessed by trypan blue staining. The expression of 93 genes involved in the process of apoptosis was determined by real-time PCR method using Taqman Low Density Array (TLDA).

Results

CEM/C1, CCRF/CEM, HL-60, HL-60/MX2 cells were exposed to DCA for 24?h. The sensitivity of each cell line to DCA is different and depends on the concentration. CEM/C1 was the most sensitive with an half-maximal inhibitory concentration (IC50) value of 30?mM, while HL-60/MX2 was the most resistant with an IC50 value of 75?mM. Exposure of leukemia cells to DCA causes differences in gene expression profiles which cannot indicate that any particular pathway of apoptosis is initiated. However, the presence of 388 statistically significant correlations between expression pattern of gens was determined.

Conclusion

We showed that DCA causes a decrease in viability of leukemia cells. The decline depends on DCA concentration. The induction of any particular apoptosis pathway is not shown in cells after DCA treatment. For that reason, studies on the molecular mechanism of cell death after exposure to DCA should be continued.  相似文献   

17.

Background

Elevated prolactin levels are associated with increased cardiometabolic risk. No previous study has compared the effect of hypolipidemic therapy on plasma levels of lipids and other cardiometabolic risk factors in patients with and without hyperprolactinemia.

Methods

The study included three age-, weight-, blood pressure- and lipid-matched groups of premenopausal women: 18 women with untreated hyperprolactinemia, 19 women with bromocriptine-treated hyperprolactinemia and 20 drug-naïve women with normal prolactin levels. Because of concomitant atherogenic dyslipidemia, all patients were treated with fenofibrate (200?mg daily) for 12 weeks. Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were assessed at baseline and at the end of hypolipidemic treatment.

Results

Unlike similar baseline lipid levels, plasma concentrations of the remaining investigated cardiometabolic risk factors were higher in women with elevated prolactin levels than in patients with normal prolactin levels. The impact of fenofibrate on total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels, as well as on uric acid, hsCRP, homocysteine, and fibrinogen was less pronounced in women with untreated hyperprolactinemia than in women with bromocriptine-treated hyperprolactinemia and drug-naïve women with normal prolactin levels.

Conclusions

The results of our study indicate that cardiometabolic effects of fenofibrate depend on plasma prolactin levels.  相似文献   

18.

Objective

To understand rural patient opinions regarding their willingness to participate in pharmacist-provided chronic condition management.

Design

Qualitative semi-structured key informant interview using The Concept of Access as a theoretical framework.

Setting

Three community pharmacies serving patients in rural Washington State from November 2016 to November 2017.

Participants

Current patients from 3 rural independent community pharmacies.

Main Outcome Measures

Qualitative analysis of patient attitudes, acceptance, perceptions, and preferences regarding pharmacist-provided chronic condition management services in a community pharmacy.

Results

Eighteen key informant interviews were conducted between November 2016 and November 2017. Five themes were identified: trust between the pharmacist, patient, and physician is key; patients already value pharmacists’ knowledge about chronic condition medications; participants identified the pharmacist as the first point of contact with regard to understanding appropriate use of medications to treat medical conditions; implementing clinical services in the community pharmacy setting may reduce the need for doctors’ visits and improve timely patient care; and creating designated clinical space, appointment options, and efficient service may increase patient accommodation.

Conclusion

Management of chronic conditions continues to be one of the largest health care expenditures in the United States. One promising method of addressing this public health concern is through sustainable clinical pharmacy services. The themes identified in this study provide insight into factors that community pharmacists might consider as medical provider status continues to gain momentum and the use of clinical pharmacy services becomes more prominent.  相似文献   

19.

Background

The increased in?ux of free fatty acids (FFAs) into the kidney is a risk factor for diabetes nephropathy (DN). In the present study we investigated the effects of astragaloside IV (AS-IV) on FFA-induced lipid accumulation, oxidative stress, and activation of TGF-β1 signaling in human glomerular mesangial cells (HMCs).

Methods

A DN model was induced in Sprague Dawley rats by the administration of a high-fat diet and streptozocin, and HMCs were stimulated with palmitate. Lipid accumulation and FFA uptake were detected using Oil Red O and BODIPY? FL C16 staining, respectively. The expression levels of TGF-β1, p-Smad2/3, FN, Col4?A1, NOX4, p22phox, and CD36 were evaluated by western blotting or immunofluorescence/immunohistochemistry. The level of reactive oxygen species (ROS) was detected using 2′,7′-dichlorofluorescein diacetate and dihydroethidium.

Results

Exposure to palmitate induced marked lipid accumulation in HMCs, whereas co-treatment with AS-IV significantly attenuated this phenomenon. Moreover, AS-IV suppressed palmitate-induced expression of TGF-β1, p-Smad2/3, FN, Col4?A1, NOX4, and p22phox, in addition to ROS production. Notably, AS-IV reduced the palmitate-induced expression of CD36 in HMCs and DN rats. Treatment of HMCs with the CD36 inhibitor, sulfo-N-succinimidyl oleate (SSO), significantly attenuated FFA uptake, oxidative stress, and fibrosis. Nevertheless, the combined use of SSO and AS-IV did not enhance the efficacy.

Conclusion

AS-IV inhibited palmitate-induced HMCs oxidative stress and fibrosis via the downregulation of CD36 expression, mediating FFA uptake and lipid accumulation.  相似文献   

20.
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