Interplay between bone marrow adiposity and bone resorption in RANKL-mediated modelled osteoporosis.

Bone marrow adipose tissue (BMAT) accrues in osteoporosis, whereas its contribution to the progression of bone resorption remains insufficiently understood. To understand the mechanisms that promote BMAT expansion in osteoporosis, in the present study, we performed extensive analysis of the spatiotemporal pattern of BMAT expansion during the progression of bone resorption in TgRANKL transgenic mouse models of osteoporosis expressing human RANKL (receptor activator of nuclear factor-κB ligand). Our results showed that TgRANKL mice of both sexes developed dramatically increased BMAT expansion compared to wild-type (WT) littermates, that was analogous to the levels of RANKL expression and the severity of the bone loss phenotype. BMAT was formed at close proximity to areas undergoing active bone remodelling and bone resorption, whereas bone resorption preceded BMAT development. Expression analysis in bone fractions demonstrated that BMAT constitutes a major source for RANKL production. Ex vivo analysis of isolated bone marrow stromal cells from TgRANKL mice showed an increased adipogenic differentiation capacity compared to WT, while osteoclast supernatants further exaggerated adipogenesis, supporting a critical role of the osteoclast-derived secretome in the differentiation of bone marrow adipocytes. Furthermore, the effectiveness of an antiosteoporosis treatment in BMAT development was investigated upon treatment of TgRANKL models with the bisphosphonate alendronate. Notably, alendronate effectively improved bone mass and attenuated BMAT expansion, indicating a possible involvement of osteoclasts and bone resorption in BMAT development. On the contrary, inhibition of BMAT with PPARγ antagonists (GW9662 or BADGE) effectively ameliorated BMAT expansion but failed to reverse the osteoporotic phenotype of TgRANKL mice. Overall, our data demonstrate that TgRANKL mice constitute unique genetic mouse models for investigating the pathogenic mechanisms that regulate the development and expansion of BMAT in osteolytic diseases.

Dimethylarginines in acute myocardial infarction: Association with lifestyle, sociodemographic, and somatometric factors.

BACKGROUND: Recent findings associate asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) with the prognosis of acute myocardial infarction (AMI). The purpose of the current study was to associate patients' lifestyle, sociodemographic, and somatometric characteristics with the time course of ADMA and SDMA concentrations in the serum of AMI patients. PATIENTS AND METHODS: In the serum of 66 AMI patients, ADMA, SDMA, troponin T, and C-reactive protein (CRP) were measured upon hospital admission (<24 h) and on the 3rd day following. Lifestyle, sociodemographic, and somatometric characteristics were obtained through a questionnaire, filled on patient discharge. RESULTS: ADMA concentrations on the 1st day positively correlated with daily reported hours of sleep (+0.497, P < 0.001) and delivery or eating out frequency (+0.285, P = 0.02), whereas it negatively correlated with reported physical condition (-0.304, P = 0.013). A personal history of hypertension indicated higher 1st-day ADMA concentration (1.818 vs 1.568, P = 0.042). Age positively correlated with 1st-day SDMA (+0.320, P = 0.009). All of the biomarker concentrations were reduced on the 3rd day measurements (P < 0.001). Self-reported lifetime minimum BMI positively correlated with either absolute (r = +0.366, P = 0.009) or percentage (r = +0.262, P = 0.045) ADMA reduction. A daily sleep in 5-8-h range was inversely correlated with percentage (-0.410, P = 0.001) or absolute (r = -0.369, P = 0.002) SDMA reduction. CONCLUSIONS: Modifiable factors such as BMI, eating habits, physical condition, and sleep seem to affect the baseline levels or time course of ADMA and SDMA in AMI patients. Changes in these factors may affect AMI prognosis by altering dimethylarginine levels.

Increasing awareness of physicians against severe leptospirosis: A treatable but potentially fatal zoonotic infection.

Leptospirosis is a worldwide, often severe and potentially fatal zoonotic infection. Here, we present the case of a 35-year-old man with severe leptospirosis infection that was identified early and was treated effectively, with a quite impressive complete recovery. Delaying of early diagnosis and treatment is crucial for the development of an unfavorable clinical course and increases the risk of a lethal outcome.

Uncontrolled diabetes resulting in diabetic cardiomyopathy in a young male patient and eventually presenting with a stroke.

Diabetic cardiomyopathy (DCP) is defined as the cardiovascular damage present in diabetes patients, which is characterized by myocardial dilatation and hypertrophy, as well as a decrease in the systolic and diastolic function of the left ventricle, and its presence is independent of the coexistence of ischemic heart disease or hypertension. As in the case of the patient that we present here, DCP may be subclinical for a long time, before the appearance of serious clinical symptoms, signs and complications. DCP is poorly recognized by most physicians. Currently, there is no specific treatment for this pathologic entity. However, proper treatment of diabetes and its metabolic abnormalities in the primary care setting reduces the rates of this serious metabolic complication of diabetes. As this high-risk diabetic population is constantly rising, increasing the awareness of physicians for the serious metabolic complications of diabetes, especially in the primary care setting, will help in taking appropriate and early action towards the prevention of full -blown disease and decreasing disability and mortality.

The role of paroxetine in fatigue and depression of patients under chemotherapeutic treatment.

We evaluated paroxetine for the treatment of fatigue and depression in patients with solid tumors after chemotherapy, and we found that paroxetine is effective for the treatment of depression during chemotherapy but has no benefit for the treatment of fatigue.

A comparative study of intravenous ibandronate and pamindronate in patients with bone metastases from breast or lung cancer: effect on metastatic bone pain.

We compared the effects of ibandronate and pamindronate in patients with bone metastases from breast or lung cancer and we found that ibandronate is superior to pamindronate in alleviating pain, improving mobility and quality of life, and reducing bone resorption indices in patients with bone metastases from breast or lung cancer.

Autoantibodies in type 1 diabetes.

Type 1 diabetes is an autoimmune disease manifested by an autoimmune attack on the pancreatic beta-islet cells. It is also known that Type 1 diabetes is associated with other autoimmune diseases. The aim of the present study was to seek autoantibodies in the serum of people with Type 1 diabetes.

An atypical presentation of visceral leishmaniasis infection in a patient with rheumatoid arthritis treated with infliximab.

Tumor necrosis factor alpha (TNF-alpha) is a cytokine, implicated in the pathogenesis of many inflammatory diseases, as well as in the immune-mediated response to infection, especially against intracellular pathogens. TNF-alpha antagonists have represented a revolution in the management of connective tissue diseases, such as rheumatoid arthritis. However, the use of these agents has been implicated with the emergence of a growing number of opportunistic infections. Here we report the case of a visceral Leishmaniasis in a 77-year-old woman who had been previously treated for rheumatoid arthritis with infliximab. The atypical presentation of this patient, previously treated with an anti-TNF-alpha biologic agent, where no splenomegaly or hepatomegaly was identified, is emphasized.

Effect of combined treatment methods on quality of life in patients with pancreatic cancer.

We aimed to analyze the effect of combined treatment methods on quality of life (QoL) in patients diagnosed with pancreatic cancer. Therefore, we prospectively analyzed 30 patients with unresectable, without distant metastases, pancreatic cancer. Patients were randomized to 1 of 2 treatment arms: radiotherapy with 5-fluorouracil or radiotherapy with gemcitabine. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire in both treatment groups. QoL was evaluated before and after treatment. We found that that both concomitant chemoradiation methods have similar impact on QoL in patients with unresectable pancreatic cancer.

A clinical study of Sotos syndrome patients with review of the literature.

Sotos syndrome is characterized by tall stature, advanced bone age, typical facial abnormalities, and developmental delay. The associated gene is NSD1. The study involved 22 patients who fulfilled the clinical criteria. Phenotypic characteristics, central nervous system findings, and cardiovascular and urinary tract abnormalities were evaluated. Meta-analysis on the incidence of cardinal clinical manifestations from the literature was also performed. Macrocephaly was present in all patients. Advanced bone age was noted in 14 of 22 patients (63%), and its incidence presented significant statistical difference in the meta-analysis of previous studies. Some patients had serious clinical manifestations, such as congenital heart defects, dysplastic kidneys, psychosis, and leukemia. Clinical and laboratory examinations should be performed to prevent and manage any unusual medical aspect of the syndrome. Facial gestalt and macrocephaly, rather than advanced bone age, are the strongest indications for clinical diagnosis.

Efficacy and safety of capecitabine and oxaliplatin combination as second-line treatment in advanced colorectal cancer.

The aim of this study was to determine the efficacy and safety of administering a combination of capecitabine and oxaliplatin in patients with advanced colorectal cancer, resistant to leucovorin/5-fluorouracil and irinotecan. Fifty-four patients with advanced colorectal cancer were prospectively evaluated (mean age 63 years, male/female 2:1) who had been previously treated with schemes containing fluoropyrimidines and irinotecan. All patients received oxaliplatin (130 mg/m2 as 2-hour intravenous infusion) the first day of the cycle and capecitabine (1000 mg/m2) twice daily, days 1-14. Cycles were repeated every 21 days until either disease progression or unacceptable toxicity. Patients were evaluated regarding their response to treatment every 9 weeks (toxicity was evaluated every 3 weeks). Total response rate was 28.3%. Median total survival was 13.5 months, and median time to progression was 5.3 months in a follow up of 24 months. Major adverse events were neutropenia, nausea, diarrhea, hand/foot syndrome, and neurotoxicity. No treatment-related or grade 4 toxicity-related deaths were observed. Additionally, no dosage decrease was required, and only 4 cycles were withheld for 1 week because of neutropenia. The combination of oxaliplatin and capecitabine is efficient and safe for patients with advanced colorectal cancer who have been previously treated with other therapeutic schemes. Furthermore, this is a convenient and well-tolerated scheme.

Smoking among high school students.

INTRODUCTION: There are no recent data on smoking habits of high-school students in Greece. The primary objective of the study was to determine these epidemiological factors. METHODS: The smoking habits of 927 high-school students (471 boys and 456 girls), aged between 15-18 years, in four regions of a Greek area (the island of Cos), were examined. Study data were collected using a questionnaire. RESULTS: It was found that 32.48% of boys and 27.19% of girls are smokers; 43.3% had started smoking before the age of 14. The mean age for starting smoking was 14.4 +/- 1.9 years for the boys and 14.9 +/- 1.6 years for the girls. As many as 22.8% of the students smoke 6 to 10 cigarettes per day and 21.5% 16 to 20 cigarettes per day; 40.2% reported that they smoke out of spite. Students reported that their parents are aware that their offspring smoke in a proportion of 36.7%. Social standards and parental example were found to be the main determinants for starting smoking. The majority of the students (95.2%) stated that they are aware of the hazards associated with smoking. DISCUSSION: Our findings highlight the need for smoking control interventions aimed at young people. Smoking is a major, yet preventable cause of morbidity and mortality. For these reasons, we view that adolescents should be targeted with a well-planned integrated anti-smoking policy and not just an initiative for raising awareness of smoking hazards.

Acute effects of smoking on skeletal muscle microcirculation monitored by near-infrared spectroscopy.

BACKGROUND: Cigarette smoking predisposes to vascular disease. Our study aimed to assess the acute effects of cigarette smoking on peripheral microcirculation using near-infrared spectroscopy (NIRS) and to compare microcirculatory function of smokers with that of nonsmokers. METHODS: We examined 65 healthy volunteers: 25 smokers (14 men and 11 women; age range, 20 to 27 years) and 40 nonsmokers (31 men and 9 women; age range, 19 to 38 years). Smokers had refrained from smoking for 2 h prior to the examination. Tissue O(2) saturation (Sto(2)), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured with a probe placed on the thenar muscle. Sto(2) baseline values were recorded for 5 min. Subsequently, the brachial artery occlusion technique was applied to evaluate microcirculatory function before, during, and after smoking one cigarette. RESULTS: Sto(2) before smoking was 85 +/- 6% (mean +/- SD), not differing significantly between men and women (84.4 +/- 6.6% vs 85.6 +/- 5.8%, respectively; p = 0.721). Sto(2) did not change significantly during smoking. O(2) consumption rate was significantly greater in women (33.4 +/- 6.7 Sto(2) U/min vs 25.7 +/- 7.1 Sto(2) U/min, p = 0.032) at baseline and throughout the smoking session. O(2) consumption rate was reduced during smoking (p < 0.001) and at 5 min after the smoking session. Smoking had a significant effect on vascular reactivity (p = 0.015), with no significant differences between genders. Five minutes after smoking, vascular reactivity had returned to approximately normal levels. CONCLUSION: Smoking acutely affects microcirculatory function. NIRS is a noninvasive, operator-independent technique that can document these effects. It seems promising for the prospective evaluation of the effects of long-term exposure to cigarette smoke.