Activity of vasopressinergic neurones of the human supraoptic nucleus is age- and sex-dependent

In the human hypothalamus, arginine-vasopressin (AVP) is produced for a major part by the neurones of the supraoptic nucleus (SON). Since plasma AVP levels in men were reported to be higher than those of women and we did not find a sex difference in the neurone number, a higher vasopressinergic neurone activity was supposed to be present in the SON of men. Therefore we studied the size of the Golgi-apparatus (GA), which has been demonstrated previously to be a sensitive parameter for protein synthetic ability of neurones, in 15 men and 17 women ranging in age from 29 to 94 years. A polyclonal antibody against immunoaffinity purified MG-160, a sialoglycoprotein of the medial cisternae of the GA was applied on paraffin-embedded sections containing the dorsolateral SON (dl-SON) from which 90-95% of neurones are vasopressinergic. SON areas that contain oxytocin (OT) cells were excluded on the basis of adjacent sections stained with a monoclonal antibody against OT. By means of an image analysis system the size of the GA and the cellular profile area were determined in dl-SON neurones with a nucleolus. Our results showed indeed an age-dependent sex difference in the size of the GA that appeared to be twice as large in young men (< or = 50 years old) than in young women of the same age. The size of the GA increased with age in women but not in men. In addition, the mean cell profile area, another measure for neuronal activity, was significantly larger in young men than in young women and was in old women larger than in young women. In conclusion, these data show the presence of a sex-dependent age-difference in the activity of vasopressinergic neurones in dl-SON which may relate to differences in AVP and sex hormone levels and kidney AVP receptors.     

A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia

Rational

A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia.

Objective

The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia.

Methods

In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8.

Results

Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699)?=?37.366, p?<?0.001] as well as negative scores [F(2.439,92.675)?=?16.623, p?<?0.001] and general psychopathology [F(1.767,67.158)?=?4.602, p?=?0.017], but not positive subscale scores [F(1.348, 51.218)?=?0.048, p?=?0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized β?=??0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups.

Conclusion

Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.     

Effects and Clinical Significance of GII.4 Sydney Norovirus,United States, 2012–2013

During 2012, global detection of a new norovirus (NoV) strain, GII.4 Sydney, raised concerns about its potential effect in the United States. We analyzed data from NoV outbreaks in 5 states and emergency department visits for gastrointestinal illness in 1 state during the 2012–13 season and compared the data with those of previous seasons. During August 2012–April 2013, a total of 637 NoV outbreaks were reported compared with 536 and 432 in 2011–2012 and 2010–2011 during the same period. The proportion of outbreaks attributed to GII.4 Sydney increased from 8% in September 2012 to 82% in March 2013. The increase in emergency department visits for gastrointestinal illness during the 2012–13 season was similar to that of previous seasons. GII.4 Sydney has become the predominant US NoV outbreak strain during the 2012–13 season, but its emergence did not cause outbreak activity to substantially increase from that of previous seasons.     

Islet Transplantation for Brittle Type 1 Diabetes: The UIC Protocol

This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin-independence with lower islet mass. Ten C-peptide negative T1DM subjects with hypoglycemic unawareness received 1–3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulin- independent. Group 1 received a mean total number of islets (EIN) of 1460   080 ± 418   330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin- independent after 1 Tx (537   495 ± 190   968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow-up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 ± 0.6 at baseline to 5.6 ± 0.5 after 2–3 Tx in Group 1 vs. 7.8 ± 1.1 to 5.8 ± 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets .     

Serum zinc and copper levels in children with chronic renal failure

We evaluated changes in serum zinc (Zn) and copper (Cu) levels in two groups of children with chronic renal failure (CRF) – children with CRF who were on regular hemodialysis (Group 1, n=40) and children with CRF who were on conservative management (Group 2, n=31) – and in one group of healthy children (Group 3, n=30). All of the participants in the study were between 5–18 years old, and the composition of the three groups was almost identical with respect to age and sex. The length of time the children in Group 1 had been on hemodialysis varied between 3 and 52 months (mean: 20.97±14.8 months). To evaluate the impact of the duration of dialysis on serum levels of Zn, we further sub-divided Group 1 patients into two subgroups: Subgroup A patients (n=20) had been on hemodialysis therapy for less than 18 months (mean: 8.85±4.83 months); Subgroup B patients (n=20) had been on hemodialysis therapy for longer than 18 months (mean: 33.1±10.86 months). The PIXE (proton-induced X-ray emission) was used for measuring the trace elements. Results: The mean serum level of Zn was lower in the Group 1 (hemodialysis group) children than in the children of Group 2 (on conservative management) and group 3 (healthy children) (p<0.001), but the difference was not significant between Groups 2 and 3. No significant differences in serum levels of Cu were found among the three groups. The serum level of Zn was lower in Subgroup B than in Subgroup A (p<0.001). The correlation test showed that there was an inverse linear relation between the length of time the child was on the hemodialysis regimen and serum Zn levels. Conclusion: Chronic hemodialysis may lead to abnormalities in the serum levels of some trace elements in children with CRF that increase in severity with increasing duration of hemodialysis. Deficiencies of these trace elements – zinc in particular – may contribute to various conditions and symptoms in children undergoing chronic hemodialysis.     

Nutrient-related issues affecting successful experimental orthotopic small bowel transplantation

BACKGROUND: This study tested the effectiveness of a nutrient-rich preservation solution in a small animal model of orthotopic whole small bowel transplantation. METHODS: Lewis rats received syngeneic total orthotopic small bowel graft after cold storage for 6 h. Donor small bowel was flushed vascularly with University of Wisconsin (UW) solution and flushed luminally with UW solution or an amino acid-rich (AA) solution as follows: Group 1, no luminal flush; Group 2, UW solution; Group 3, AA solution. Biopsies were taken over 14 days posttransplant; energetics, oxidative stress, neutrophil recruitment and histologic injury were assessed. RESULTS: All animals in Groups 1 and 2 failed to survive 12 h posttransplant due to hemorrhagic shock and fluid loss. In contrast, all animals in Group 3 survived the operation; survival after 14 days was 80% (4/5). In Group 3, full recovery of tissue adenylates (ATP and energy charge) to freshly isolated tissue values occurred within 3 days. Oxidative stress as assessed by malondialdehyde (MDA) levels was low in Group 3 throughout 14 d; Groups 1 and 2 exhibited high oxidative stress over the initial 35 min reperfusion (P<0.05). Neutrophil recruitment (myeloperoxidase activity) was significantly reduced in Group 3 tissues, as was histologic injury (P<0.05 compared to Groups 1 and 2). By day 14, Group 3 exhibited complete mucosal restoration. CONCLUSIONS: The data presented in this communication supports the use of an intraluminal preservation solution that is tailored to the metabolic requirements of the small bowel.     

Abnormal left ventricular relaxation and symptoms of heart failure

Objectives

The purpose of our study was to assess the echocardiographic and angiographic parameters in patients with symptomatic heart failure (HF) and mild diastolic dysfunction (grade I).

Background

It remains uncertain why some patients with mild diastolic dysfunction exhibit HF symptoms and others are asymptomatic.

Methods

The study enrolled 80 hospitalized patients with impaired left ventricular (LV) relaxation. Patients were divided into two groups; one group had chronic functional class II to III dyspnea and the other group had no symptoms of HF. After admission, echocardiography and coronary angiography were performed for all patients and LV systolic and diastolic parameters were compared between the two groups.

Results

More patients in the asymptomatic group were hypertensive (p-value: 0.012). However, coronary artery disease was more prevalent in symptomatic patients (p-value: 0.022). The LV ejection fraction (EF) was significantly lower in symptomatic patients [median 54.33 %, 95 % confidence interval (53.76–54.87 %) in asymptomatic patients and median 49.43, 95 % confidence interval (47.23–50.91 %) in symptomatic patients, p-value <0.001]. Furthermore, the systolic LV internal dimension was significantly larger in this group (p-value: 0.037). The results of logistic regression identified that only the absolute level of the LVEF was the negative determinant of the occurrence of HF in patients with impaired LV relaxation.

Conclusion

Our study showed that LV systolic performance has an important role in occurrence of HF symptoms in patients with grade I diastolic dysfunction.

     

Unusual transmission route of Lymphogranuloma venereum; following sexual contact with a female donkey

Here, we present a 20-year-old man who presented with painful inguinal and femoral masses. He gave a history of sexual contact with a mare 14 days before his recent illness. He was diagnosed with lymphogranuloma venereum based on the histopathological findings and a high titre of IgG (1:1400).     

Toxic effects arising from selenium and deferasirox interaction in the biological system

This investigation was conducted to evaluate the effect of deferasirox on selenium toxicity in male rat organs. After 50 days of selenium administration, all the rats showed toxicity symptoms. After poisoning, deferasirox was given orally to rats during 10 days. The results show that toxicity symptoms were unexpectedly increased. The new symptoms of toxicity after deferasirox administration were including loss of body hairs, yellowish discoloration of hair, weakness, brown spot on their skin, enlargement of the spleen and shrinking of sex organs. Selenium and iron concentrations were determined by GFAAS and FAAS, respectively. The results indicate the poisoned rats with selenium that received deferasirox as a drug, shown serious symptoms such as exacerbate toxicity, reduction in iron concentration, anemia and even death after a few days of deferasirox administration.