Chronic central leptin infusion differently modulates brain and liver insulin signaling

Recent studies reported the impact of leptin on peripheral insulin sensitivity and glucose utilization. However, little is known concerning the effect of central leptin on hypothalamic and hepatic insulin efficiency. This study aimed to determine the consequence of chronic intra-cerebroventricular (ICV) leptin or murine leptin antagonist (MLA) infusion on hypothalamic and hepatic insulin signaling pathways, in rats. A 2-week central leptin infusion enhanced insulin-dependent Akt phosphorylation in the liver without changing PTP-1B protein expression, associated to insulin receptor (IR) upregulation and reduced IRS-1 phosphorylation on Ser302 residue. In the hypothalamus, a chronic ICV leptin infusion induced PTP-1B associated with a specific decrease in insulin-dependent Akt phosphorylation. In contrast, a chronic MLA infusion did not alter IR and PTP-1B expressions in hypothalamus and liver. Our results underline a brain leptin-dependent increase in hepatic insulin efficiency as mirrored by IR up-regulation, increased insulin-dependent Akt phosphorylation and reduced IRS-1 phosphorylation on Ser302 residue.     

Neonatal handling and gender modulate brain monoamines and plasma corticosterone levels following repeated stressors in adulthood

Neonatal handling affects the response to repeated stress in a sexually dimorphic manner. In order to elucidate the mechanisms underlying these gender-dependent effects, we investigated the consequences of neonatal androgenization and handling on adult stress reactivity by determining: (a) immobility time during repeated forced swimming, (b) plasma corticosterone levels, and (c) brain serotonin and dopamine levels and turnover after either repeated forced swimming, or repeated forced swimming followed by repeated restraint stress. In neonatally androgenized females, immobility time was lower in the handled than in the non-handled rats, a pattern resembling that of the males, suggesting that the sexually dimorphic effect of handling on immobility time can be attributed to the organizational effects of testosterone. No differences were found between androgenized females and females injected neonatally with vehicle, indicating that the gender differences in circulating corticosterone are not due to the organizational effects of testosterone. The stress of a neonatal injection interacted with neonatal handling resulting in lower plasma corticosterone and hypothalamic dopamine and serotonin levels in the neonatally injected handled animals following repeated forced swimming. The serotonergic system appears to be sensitive to both the organizational actions of testosterone and the effects of handling, since handled androgenized females had higher serotonin levels and decreased turnover following repeated forced swimming stress, compared to those injected neonatally with vehicle. Handling resulted in increased hypothalamic and striatal serotonin levels in both males and females following repeated forced swimming. Our results reveal that handling has gender-dependent effects on adult hypothalamic-pituitary-adrenal axis and brain monoaminergic system reactivity to stress and that these effects can be attributed to both the organizational and activational effects of gonadal hormones.     

Epidemiology of ATTRV30M neuropathy in Cyprus and the modifier effect of complement C1q on the age of disease onset

Abstract

Background: ATTRV30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by amyloid deposition composed of aggregated misfolded TTR monomers with the V30M mutation. The age of onset in patients with ATTRV30M varies in different foci and the mechanism behind it is still unknown.

Methods: The tertiary neurology center following all ATTRV30M patients in Cyprus was used to collect demographic data to estimate; prevalence, incidence, penetrance, anticipation, time from disease onset to diagnosis and transplantation. Ocular, cardiac and leptomeningeal involvement in transplanted patients was explored. Correlation of C1q tagging SNPs with age of disease onset was carried out.

Results: Prevalence and incidence for ATTRV30M neuropathy in Cyprus are 5.4/100,000 and 0.3/100,000 respectively. Mean age of onset is 40.6 years and anticipation is 8.3?years. Penetrance reaches 51% and 75% by the ages of 50 and 80?years respectively. In liver transplanted patients rates of ocular, cardiac and leptomeningeal involvement were estimated to be 60%, 20% and 16%, respectively. C1q polymorphisms correlated with age of disease onset.

Conclusions: ATTRV30M neuropathy has a rising prevalence in Cyprus due to improved survival of patients. Late onset complications are becoming a major problem. Complement C1q appears to be a modifier in this disease.     

Treatment of stage III-A-1 and III-B-1 periprosthetic knee infection with two-stage exchange arthroplasty and articulating spacer

The incidence of periprosthetic knee infection is generally low, but the economic impact is great. Treatment should take into account the acuteness of the infection, the overall immune/medical status of the patient, and the local factors at the site of the infection. The aim of this study was to evaluate the two-phase exchange arthroplasty with the use of antibiotic-impregnated articulating spacer, as an alternative treatment of chronic periprosthetic knee infection in patients with minimum systemic and no local compromising factors. Staphylococcus aureus was the most common pathogen followed by Staphylococcus epidermidis and Pseudomonas aeruginosa. Twenty-four patients were treated with this regiment. All of them returned to normal everyday activity and no infection recurrence was noted over a 2- to 10-year follow-up. Excellent long-term results can be achieved for patients staged as III-A-1 and III-B-1 according to the Musculoskeletal Infection Society staging system, when treated with the aforementioned protocol and intravenous antibiotics.     

Screening for preparatory grief in advanced cancer patients

The present study aims to determine the use of Preparatory Grief in Advanced Cancer Patients (PGAC) Scale for screening preparatory grief according to independent criterion standards (ie, the Hospital Anxiety and Depression [HAD] Total scale and the HAD Depression and Anxiety subscales) and to establish an optimal cutoff point for discriminating between subjects with and without preparatory grief. One hundred advanced cancer patients treated in a Pain Relief and Palliative Care Unit completed the PGAC and HAD Scales, while researchers recorded data on demographic characteristics, disease status, and treatment regimen. Optimal balance between sensitivity and specificity for the PGAC Scale as a screening instrument was achieved at a cutoff score of 40+ for all the criterion standards (ie, HAD Total, HAD Anxiety, and HAD Depression), giving a sensitivity range between 84% and 92%, and specificity between 70% and 86%. The area under the receiver operating characteristic curve ranged between 0.867 and 0.968. The PGAC Scale had a favorable sensitivity and specificity in identifying cases of preparatory grief. The receiver operating characteristic analyses demonstrated that the scale is a useful screening instrument in advanced cancer patients.     

Acute uncomplicated cystitis: from surveillance data to a rationale for empirical treatment

The objectives of this study were to explore the epidemiological features and resistance rates in uropathogens isolated from cases of acute uncomplicated cystitis (AUC) in Greece, and subsequently to guide empirical treatment. Urine samples from outpatients aged >16 years were cultured and for each uropathogen isolated non-susceptibility to orally administered antimicrobial agents was defined. Demographic and clinical data were provided in questionnaire form. From January 2005 to March 2006 a total of 1936 non-duplicate positive urinary cultures were collected and 889 AUC cases were evaluated. Escherichia coli was the main aetiological agent (83%). In the AUC group, non-susceptibility rates for E. coli isolates were as follows: amoxicillin 25.8%; co-trimoxazole 19.2%; cefalothin 14.9%; nitrofurantoin 10.7%; amoxicillin/clavulanic acid 5.2%; nalidixic acid 6%; mecillinam 3.4%; ciprofloxacin 2.2%; cefuroxime 1.7%, and fosfomycin 1.6%. Amoxicillin and/or co-trimoxazole use in the previous 3 months was significantly associated with isolation of a co-trimoxazole-resistant E. coli isolate. The same applied for previous use of a fluoroquinolone agent and isolation of a ciprofloxacin-resistant E. coli isolate. In conclusion, increased co-trimoxazole non-susceptibility rates undermine its use as a first-line agent in empirical treatment, especially in cases of recent use of co-trimoxazole and/or amoxicillin. Fluoroquinolones display potent in vitro activity against community uropathogens, but prudent use is warranted for uncomplicated infections. Mecillinam and nitrofurantoin could serve as effective front-line agents in an effort to design fluoroquinolones-sparing regimens.     

Depression, hopelessness, and sleep in cancer patients' desire for death

OBJECTIVE: The aim of this study was to evaluate the prevalence of clinical characteristics and risk factors for hastened death in advanced cancer patients. METHODS: Patients completed the Greek version of Schedule of Attitudes toward Hastened Death (G-SAHD), a sleep quality measure, the Pittsburgh Sleep Quality Index (PSQI), a Greek version of a depression inventory, the Beck Depression Inventory (BDI), a hopelessness scale, the Beck Hopelessness Scale (BHS), and a Visual Analogue Scale (VAS) for the assessment of pain. PATIENTS: The final sample consisted of 102 terminally ill cancer patients attending a Palliative Care Unit. RESULTS: Statistically significant associations were found between G-SAHD and patients performance status (ECOG) (chi2 = 8.62, p = 0.003). Strongest associations were observed between desire for death, depression, and hopelessness (r = 0.468, p < 0.0005, r = 0.678, p < 0.0005, respectively). In the prediction of G-SHAD the contribution of "hopelessness" (p < 0.0005), "depression" (p < 0.0005), "use of sleeping medication" (p < 0.0005), and "sleep quality" (p = 0.001) was high (59% of variance). CONCLUSION: Depression, hopelessness, and sleep quality appeared to have a statistically significant relationship with desire for hastened death. Health care professionals finding desire for death in advanced cancer patients should not only consider depression and hopelessness, but also other factors such as poor sleep quality in their diagnostic formulations in order to provide the appropriate treatment.     

Brief cognitive assessment of cancer patients: evaluation of the Mini-Mental State Examination (MMSE) psychometric properties

AIM: The aim of the present study was to validate the Greek version of the MMSE in advanced-cancer patients attending a palliative care unit. METHODS: The sample consisted of 103 advanced-cancer patients. The questionnaire was completed at baseline and three days later. Together with the MMSE, the patients also completed the EORTC QLQ-C30 Cognitive functioning scale, while researchers recorded data on demographic characteristics, disease status and treatment regimen. RESULTS: MMSE had overall Cronbach alpha 0.890. Validity as performed using known-group analysis showed good results. MMSE discriminated well between subgroups of patients differing in disease severity as defined by ECOG performance status. Comparison between the MMSE and the EORTC Cognitive functioning scale was statistically significant (p<0.05). CONCLUSION: These psychometric properties of the Greek version of the MMSE confirm it as a valid and reliable measure when administered to patients with advanced cancer.