Early Effects Triggered by Larrea divaricata Cav. on Murine Macrophages at Apoptotic Concentrations

Decoction and infusion of Larrea divaricata were tested at apoptotic concentrations (1 and 4 mg/ml) on peritoneal murine macrophages. Consistent changes were observed after incubation with 4 mg/ml decoction. Phagocytosis of zymosan, lysosomal enzyme activity, nitric oxide production, TNF-α release, and expression of CD14, TLR4, and CR3 increased significantly. Decoction at 1 and 4 mg/ml increased the binding of LPS-FITC. Apoptosis triggered by L. divaricata decoction is consequence of cell activation. The effects are independent of nordihydroguaiaretic acid. This “activation and death” could be the mechanism of L. divaricata to exert the antituberculosis effect known in folk medicine.     

Cordoma condroide de localización atípica

Chondroid chordoma is an extremely rare tumour with an annual incidence of around 0.1 cases per 100,000 population. Involvement of the thoracic vertebrae may be present in 2-5% of cases.     

Diseño de una vía clínica para la atención a los pacientes con esclerosis múltiple

IntroductionClinical pathways are standard health care methods to coordinate clinical work, reduce inter-clinician variability, improve patient care and increase staff and patient satisfaction. The aim of this study is to develop a clinical pathway capable of organising and developing standard procedures for diagnosis, treatment and care in patients with multiple sclerosis and to coordinate all medical specialists involved in this disease.MethodsA multidisciplinary unit for the care of MS patients was developed. All of them and quality specialists analysed some international evidence-based studies, clinical guides, international guidelines and other clinical neurological pathways in several meetings and designed several documents for the clinical pathways.ResultsA clinical pathway was created consisting of a scientific-technical framework, which arranges the care in relation to the diagnosis and reatment. The framework is accompanied by various patient-information documents on the disease, an information sheet on diagnostic procedures and a map of the process. Quality standards were established to achieve continuous improvement in patient care.ConclusionsA clinical pathway for the care of MS patients in a multidisciplinary unit homogenises and organises the care which the MSpatient should receive from the initial symptoms to the progressive stages. This clinical pathway improves the quality of patient care, reduces the variability in work protocols and rationalises the use of the available health care resources.     

Hot flushes

Almost every woman and some men will encounter hot flushes during their lifetime. Despite the prevalence of the symptoms, the pathophysiology of hot flushes remains unknown. A decline in hormone concentrations might lead to alterations in brain neurotransmitters and to instability in the hypothalamic thermoregulatory setpoint. The most effective treatments for hot flushes include oestrogens and progestagens. However, many women and their physicians are reluctant to accept hormonal treatments. Women want non-pharmacological treatments but unfortunately such treatments are not very effective, and non-hormonal drugs are often associated with adverse effects. Results from recent studies showed that selective serotonin reuptake inhibitors and other similar compounds can safely reduce hot flushes. Moreover, the efficacy of these drugs provides new insight into the pathophysiology of hot flushes. In this critical review, we assess knowledge of the epidemiology, pathophysiology, and treatment of hot flushes.     

Tacrolimus as an Effective and Durable Second-Line Treatment for Chronic Autoimmune Hepatitis: A Multicentric Study

Digestive Diseases and Sciences - Autoimmune hepatitis (AIH) is a chronic liver disease able to progress to acute liver failure, cirrhosis, and liver cancer. A significant proportion of patients...     

Novel risk factors for peripheral arterial disease in young women

PURPOSE: To investigate traditional and novel risk factors (homocysteine and C-reactive protein levels, and exposure to infections) for peripheral arterial disease in young women. SUBJECTS AND METHODS: In a multicenter, population-based, case-control study, 212 young women (mean [+/- SD] age, 48.2 +/- 7.0 years) with peripheral arterial disease and 475 healthy control women (mean age, 45.5 +/- 8.1 years) completed a standardized questionnaire and provided blood samples. Peripheral arterial disease was angiographically confirmed if a stenotic lesion (more than 50% reduction of the lumen) was present in at least one major peripheral artery. Hyperhomocysteinemia was defined as a nonfasting plasma homocysteine level exceeding the 90th percentile of the control group. History of infectious diseases was determined by questionnaire. RESULTS: Elevated C-reactive protein levels were associated with an increased likelihood of peripheral arterial disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.8 to 8.5 for women in the third quartile; OR = 3.1; 95% CI: 1.4 to 6.8 for women in the fourth quartile; both comparisons with women in the first quartile). Hyperhomocysteinemia was not associated with a significantly increased risk of peripheral arterial disease (OR = 1.6; 95% CI: 0.9 to 3.0). A history of chickenpox, shingles, mumps, pneumonia, chronic bronchitis, peptic ulcer, or periodontitis was independently related to peripheral arterial disease, with adjusted odds ratios varying from 1.7 (95% CI: 1.0 to 3.1) for mumps to 3.4 (95% CI: 1.5 to 7.7) for peptic ulcer. The risk of peripheral arterial disease increased with the number of these infections; exposure to five or more infections increased the odds 3.7-fold (95% CI: 1.7 to 8.2). This association was not affected by the level of C-reactive protein. CONCLUSION: Our results do not support a strong relation between homocysteine and peripheral arterial disease in young women. However, an elevated C-reactive protein level and several types of symptomatic infection were associated with peripheral arterial disease.     

Risk of progression to AIDS and death in women infected with HIV-1 initiating highly active antiretroviral treatment at different stages of disease

BACKGROUND: The optimal virologic and immunologic stage at which to initiate antiretroviral therapy in individuals infected with human immunodeficiency virus type 1 (HIV-1) is undefined. METHODS: Among 1054 HIV-1-infected women in a prospective cohort study, we determined the time from initiation of highly active antiretroviral treatment (HAART) to acquired immunodeficiency syndrome (AIDS) and death. RESULTS: Median follow-up was 3.4 years. Of 553 women without AIDS at HAART initiation, 62 (11%) developed AIDS. Compared with women with CD4(+) cell counts greater than 350/microL at HAART initiation, women with cell counts of 200 to 350/microL and less than 200/microL had relative hazards (RHs) for progression to AIDS of 0.93 (95% confidence interval [CI], 0.46-1.86) and 2.48 (95% CI, 1.39-4.42), respectively. Compared with those with HIV-1 RNA values less than 5000 copies/mL, women with 5000 to 50,000 copies/mL and greater than 50,000 copies/mL had RHs of 1.39 (95% CI, 0.74-2.64) and 2.09 (95% CI, 1.09-3.99), respectively. Among women with AIDS at HAART initiation (n = 501), RHs of death were 1.97 (95% CI, 0.84-4.66) and 3.35 (95% CI, 1.59-7.08) with CD4(+) cell counts of 200 to 350/microL and less than 200/microL, respectively, relative to those with greater than 350/microL, and 1.90 (95% CI, 0.84-4.30) and 3.70 (95% CI, 1.81-7.54) for those with HIV-1 RNA values of 5000 to 50,000 and greater than 50,000 copies/mL, respectively, relative to those with less than 5000 copies/mL. CONCLUSIONS: Progression to AIDS and death was predicted by pre-HAART values of less than 200/microL for CD4(+) cells and greater than 50,000 HIV-1 RNA copies/mL, indicating that deferral of HAART until the CD4(+) cell count is between 350 and 200/microL is a valid strategy in the clinical management of HIV-1 infection.     

Trends in Medicare Part D Medication Therapy Management Eligibility Criteria

Background

To increase the enrollment rate of medication therapy management (MTM) programs in Medicare Part D plans, the US Centers for Medicare & Medicaid Services (CMS) lowered the allowable eligibility thresholds based on the number of chronic diseases and Part D drugs for Medicare Part D plans for 2010 and after. However, an increase in MTM enrollment rates has not been realized.

Objectives

To describe trends in MTM eligibility thresholds used by Medicare Part D plans and to identify patterns that may hinder enrollment in MTM programs.

Methods

This study analyzed data extracted from the Medicare Part D MTM Programs Fact Sheets (2008–2014). The annual percentages of utilizing each threshold value of the number of chronic diseases and Part D drugs, as well as other aspects of MTM enrollment practices, were analyzed among Medicare MTM programs that were established by Medicare Part D plans.

Results

For 2010 and after, increased proportions of Medicare Part D plans set their eligibility thresholds at the maximum numbers allowable. For example, in 2008, 48.7% of Medicare Part D plans (N = 347:712) opened MTM enrollment to Medicare beneficiaries with only 2 chronic disease states (specific diseases varied between plans), whereas the other half restricted enrollment to patients with a minimum of 3 to 5 chronic disease states. After 2010, only approximately 20% of plans opened their MTM enrollment to patients with 2 chronic disease states, with the remaining 80% restricting enrollment to patients with 3 or more chronic diseases.

Conclusion

The policy change by CMS for 2010 and after is associated with increased proportions of plans setting their MTM eligibility thresholds at the maximum numbers allowable. Changes to the eligibility thresholds by Medicare Part D plans might have acted as a barrier for increased MTM enrollment. Thus, CMS may need to identify alternative strategies to increase MTM enrollment in Medicare plans.     

FM19G11 reverses endothelial dysfunction in rat and human arteries through stimulation of the PI3K/Akt/eNOS pathway,independently of mTOR/HIF-1α activation

Background and Purpose

FM19G11 up-regulates mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α) and PI3K/Akt pathways, which are involved in endothelial function. We evaluated the effects of FM19G11 on defective endothelial vasodilatation in arteries from rats and humans and investigated the mechanisms involved.

Experimental Approach

Effects of chronic in vivo administration of FM19G11 on aortic endothelial vasodilatation were evaluated together with ex vivo treatment in aortic and mesenteric arteries from control and insulin-resistant rats (IRR). Its effects on vasodilator responses of penile arteries (HPRAs) and corpus cavernosum (HCC) from men with vasculogenic erectile dysfunction (ED) (model of human endothelial dysfunction) were also evaluated. Vascular expression of phosphorylated-endothelial NOS (p-eNOS), phosphorylated-Akt (p-Akt) and HIF-1α was determined by immunodetection and cGMP by elisa.

Key Results

Chronic administration of FM19G11 reversed the impaired endothelial vasodilatation in IRR. Ex vivo treatment with FM19G11 also significantly improved endothelium-dependent vasodilatation in aorta and mesenteric arteries from IRR. These effects were accompanied by the restoration of p-eNOS and cGMP levels in IRR aorta and were prevented by either NOS or PI3K inhibition. p-Akt and p-eNOS contents were increased by FM19G11 in aortic endothelium of IRR. FM19G11-induced restoration of endothelial vasodilatation was unaffected by mTOR/HIF-1α inhibitors. FM19G11 also restored endothelial vasodilatation in HPRA and HCC from ED patients.

Conclusions and Implications

Stimulation of the PI3K/Akt/eNOS pathway by FM19G11 alleviates impaired NO-mediated endothelial vasodilatation in rat and human arteries independently of mTOR/HIF-1α activation. This pharmacological strategy could be beneficial for managing pathological conditions associated with endothelial dysfunction, such as ED.     

Acute intermittent porphyria and chronic transaminase elevation

Acute intermittent porphyria is an autosomal dominant inherited disorder resulting from a deficiency of porphobilinogen deaminase activity, the third enzyme in the heme biosynthesis pathway. This disease is uncommon, although the prevalence is higher in asymptomatic heterozygotic carriers; however, this prevalence is difficult to establish because of the absence of symptoms. Although acute intermittent porphyria is a multisystemic disease, its most common form of presentation is abdominal pain and neurological or mental symptoms, which can sometimes be due to precipitating factors such as reduced energy intake, smoking, alcohol, some drugs, and stress. Diagnosis can be made by testing urinary porphobilinogen levels, with subsequent measurement of enzyme activity and DNA testing. Treatment is based on prevention of porphyria attacks by avoiding precipitating factors and early administration of intravenous glucose or hemin therapy. We present the case of a patient diagnosed with acute intermittent porphyria based on study of chronic mild alanine aminotransferase (ALT) elevation.