Experimental inflammation and tumor growth

Development and growth of primary (methylcholantrene or benzpyrene-induced) sarcomas in adjuvant arthritic rats were investigated and compared with the chemical carcinogenesis in normal healthy animals. When carcinogen and adjuvant were applied in the same time, tumor development and growth rate did not differ significantly from nonarthritic controls. When carcinogen was applied to rats with fully established arthritic disease, development and growth of tumors were significantly enhanced. In the latter case local and systemic adjuvant disease was more severe in tumor-bearing rats. Enhanced chemical carcinogenesis in arthritic rats can be explained by a defective immune responsiveness in the chronic stage of arthritis.     

Serum copper and zinc concentrations in patients with chronic hepatitis C

The aim of this study was to measure the alterations in serum trace elements, including zinc and copper in patients with chronic hepatitis C and to compare them with the results of healthy individuals. Seventeen patients with chronic hepatitis C and 17 healthy individuals were included in this study. Serum zinc and cooper concentrations were measured by using atomic absorption spectrophotometer of patients with chronic hepatitis C and the results were statistically compared with those of healthy individuals. Serum zinc concentrations were 105.6+/-22.8 microg/dl in patients with chronic hepatitis C and 94.41+/-19 microg/dl in healthy controls, respectively. Serum copper concentrations were 103.17+/-20.8 microg/dl in patients with chronic hepatitis C and 90.8+/-14.3 microg/dl in healthy subjects, respectively. Serum zinc and copper concentrations were not found statistically different in patients with chronic hepatitis C compared with those of healthy individuals (p>0.05). In conclusion, serum trace element concentrations did not show statistical alterations in patients with chronic hepatitis C compared to healthy subjects.     

Implementation of HIV early infant diagnosis and HIV type 1 RNA viral load determination on dried blood spots in Cameroon: challenges and propositions

The testing of dried blood spots (DBSs) for human immunodeficiency type 1 (HIV-1) proviral DNA by PCR is a technology that has proven to be particularly valuable in diagnosing exposed infants. We implemented this technology for HIV-1 early infant diagnosis (EID) and HIV-1 RNA viral load determination in infants born of HIV-1-seropositive mothers from remote areas in Cameroon. The samples were collected between December 2007 and September 2010. Fourteen thousand seven hundred and sixty-three (14,763) DBS samples from infants born of HIV-positive mothers in 108 sites nationwide were tested for HIV. Of these, 1452 were positive on first PCR analyses (PCR1), giving an overall infection rate of 12.30%. We received only 475 DBS specimen for a second PCR testing (PCR2); out of these, 145 were positive. The median HIV-1 RNA viral load for 169 infant DBS samples tested was 6.85 log copies/ml, with values ranging from 3.37 to 8 log copies/ml. The determination of the viral load on the same DBS as that used for PCR1 allowed us to bypass the PCR2. The viral load values were high and tend to decrease with age but with a weak slope. The high values of viral load among these infants call for early and effective administration of antiretroviral therapy (ART). The findings from this study indicate that the use of DBS provides a powerful tool for perinatal screening programs, improvement on the testing algorithm, and follow-up during treatment, and thus should be scaled up to the entire nation.     

The Hypotonic Environmental Changes Affect Liposomal Formulations for Nose-to-Brain Targeted Drug Delivery

Systemic administration of drugs is ineffective in the treatment of central nervous system disorders because of the blood-brain barrier. Nasal administration has been suggested as an alternative administration route as drugs absorbed in the olfactory epithelium bypass the blood-brain barrier and reach the brain within minutes. However, the nasal mucosa properties (e.g., tonicity, pH) are not constant because of physiological and environmental factors, and this might limit the therapeutic outcome of nanocarrier-based formulations. To shine light on the impact of environmental ionic strength on nanocarrier-based formulations, we have studied how liposomal formulations respond to the change of tonicity of the external environment. Large unilamellar vesicles loaded with 6 different drugs were exposed to different hypotonic environments, creating an osmotic gradient within the inner core and external environment of the liposomes up to 650 mOsm/kg. Both size and polydispersity of liposomes were significantly affected by tonicity changes. Moreover, the release kinetics of hydrophilic and lipophilic drugs were largely enhanced by hypotonic environments. These results clearly demonstrate that the environmental ionic strength has an impact on liposomal formulation stability and drug release kinetics and it should be considered when liposomal formulations for nose-to-brain targeted drug delivery are designed.     

Augenbefall und Systemerkrankung – periokuläre und intraokuläre Lymphome

Die Onkologie - Das okuläre Lymphom wird anhand seiner anatomischen Lokalisation in die intraokulären und periokulären Lymphome eingeteilt. Intraokulär kann die Uvea mit ihren...     

Hippocampal asymmetry in the behavioral responses to the 5-HT1A receptor agonist 8-OH-DPAT

The present study examined the behavioral responses of rats to unilateral and bilateral injections of the selective serotonin 1A (5-HT1A)-receptor agonist 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) 1 μg into the hippocampal CA1 area of male Wistar rats. 8-OH-DPAT increased locomotor activity, which was most pronounced with injections into the left hippocampus. The agonist impaired learning and memory (shuttle-☐), especially when injected into the right hippocampus. The elevated plus-maze experiments showed that neither left nor right nor bilateral hippocampal injections of 8-OH-DPAT produced any anxiogenic effect. However, with Vogel's conflict test, right injections of 8-OH-DPAT produced anxiety. The present study has revealed hippocampal asymmetry in the behavioral responses to the 5-HT1A-receptor agonist 8-OH-DPAT.     

The work profile of family caregivers of persons affected by HIV/AIDS

In Switzerland, HIV incidence has increased considerably during the past two years. This fact has raised concern both in the media and in the health care system. However family caregivers have not been considered in these debates, although their figures are increasing as well. In Switzerland, a few research studies were conducted focussing on the situation of family caregivers affected by HIV/AIDS. This particular qualitative research project focuses on the questions as to what kind of work these family caregivers are doing, under which conditions they are working, and which consequences arise from their work. Data were collected by conducting eleven semi-structured interviews, and data analysis was done through a content analysis. Results show that family caregivers provide a wide range and a large amount of family work. Not only are family caregivers working for the HIV-positive persons, but also for the benefit of other family members and friends as well as for themselves. Family caregivers achieve mainly stable life situations for their HIV-positive family member. The discussion focuses on the dynamics of family work which requires constant adaptations in daily life. In addition, ordinary family work needs to be noticed and appreciated in symbolic, social, and financial terms. Finally, implications for nursing practice are considered.     

Telomere instability detected in sporadic colon cancers, some showing mutations in a mismatch repair gene

Human telomeres are essential for genome stability and are composed of long simple tandem repeat arrays (STRs), comprising the consensus TTAGGG repeat interspersed, at the proximal end, with sequence-variant repeats. While the dynamics of telomere attrition through incomplete replication has been studied extensively, the effects on telomeres of error-prone DNA repair processes, known to affect other STRs, are poorly understood. We have compared the TTAGGG and sequence-variant interspersion patterns in the proximal 720 bp of telomeres in colon cancer and normal DNA samples. The frequency of telomere mutations was 5.8% per allele in a randomly collected panel of sporadic colon cancers, showing that telomere mutations occur in vivo. The mutation frequency rose to 18.6% per allele in sporadic tumours that exhibit instability at the polyA tract in the TGFbetaRII gene and to 35% per allele in tumours with somatic mutations in the hMSH2 gene. The majority of the characterized mutations resulted in the loss of one or a few repeats. If the mutation spectrum and frequency described here is reiterated in the rest of the array, there is the potential for extensive telomere destabilization especially in mismatch repair-defective cells. This may in turn lead to a greater requirement for telomere length maintenance earlier in tumourigenesis.     

Influence of moderate and profound hyperventilation on cerebral blood flow, oxygenation and metabolism

OBJECTIVE: The aim of the present study was to examine the impact of moderate and profound hyperventilation on regional cerebral blood flow (rCBF), oxygenation and metabolism. MATERIALS AND METHODS: Twelve anesthetized pigs were subjected to moderate (mHV) and profound (pHV) hyperventilation (target arterial pO(2): 30 and 20 mmHg, respectively) for 30 min each, after baseline normoventilation (BL) for 1 h. Local cerebral extracellular fluid (ECF) concentrations of glucose, lactate, pyruvate and glutamate as well as brain tissue oxygenation (p(ti)O(2)) were monitored using microdialysis and a Licox oxygen sensor, respectively. In nine pigs, regional cerebral blood flow (rCBF) was also continuously measured via a thermal diffusion system. RESULTS: Both moderate and profound hyperventilation resulted in a significant decrease in rCBF (BL: 37.9+/-4.3 ml/100 g/min; mHV: 29.4+/-3.6 ml/100 g/min; pHV: 23.6+/-4.7 ml/100 g/min; p<0.05) and p(ti)O(2) (BL: 22.7+/-4.1 mmHg; mHV: 18.9+/-4.9 mmHg; pHV: 13.0+/-2.2 mmHg; p<0.05). A p(ti)O(2) decrease below the critical threshold of 10 mmHg was induced in three animals by moderate hyperventilation and in five animals by profound hyperventilation. Furthermore, significant increases in lactate (BL: 1.06+/-0.18 mmol/l; mHV: 1.36+/-0.20 mmol/l; pHV: 1.67+/-0.17 mmol/l; p<0.005), pyruvate (BL: 46.4+/-7.8 micromol/l; mHV: 58.0+/-10.3 micromol/l; pHV: 66.1+/-12.7 micromol/l; p<0.05), and lactate/glucose ratio were observed during hyperventilation. (Data are presented as mean+/-S.E.M.) CONCLUSIONS: Both moderate and profound hyperventilation may result in insufficient regional oxygen supply and anaerobic metabolism, even in the uninjured brain. Therefore, the use of hyperventilation cannot be considered as a safe procedure and should either be avoided or used with extreme caution.