Changes of ocular higher order aberration in on- and off-eye of rigid gas permeable contact lenses.

PURPOSE: To investigate ocular higher order aberration (HOA) changes caused by rigid gas permeable (RGP) contact lens (CL) wear. METHODS: Twenty-two eyes of 22 myopic patients and 14 eyes of 14 keratoconic patients who were fitted with an RGP CL were enrolled to examine ocular HOAs using a Hartmann-Shack wavefront sensor before and after RGP wear. Root mean square (RMS) values and Zernike coefficients in RGP-on and RGP-off eyes were compared for both myopic and keratoconic eyes, or between patient groups divided according to their prefitted total HOA value (RMS<0.33 microm or>or=0.33 microm in myopic eyes and RMS<0.46 microm or>or=0.46 microm in keratoconic eyes). All HOA values were recomputed for a 4-mm pupil for comparison purposes. RESULTS: In keratoconic eyes, RGP CL changed the direction of vertical coma from -0.185 to 0.134 microm (p=0.024). In the low HOA myopic group, total HOA increased from 0.23 to 0.35 microm (p=0.006) by RGP CL wear, mainly due to increased coma aberration from 0.0951 to 0.2146 microm (p=0.006). The direction of vertical coma changed from the inferior to superior cornea in the low HOA group (p=0.020). In the high HOA keratoconic group, total HOA decreased from 0.54 to 0.36 microm (p=0.049), and the direction of the vertical coma changed from the inferior to superior cornea (p=0.049). CONCLUSIONS: RGP CL wear may enhance or reduce HOA based on original existing ocular aberration mainly through directional changes in vertical coma.     

Chronic Administration of Ketamine Elicits Antidepressant‐Like Effects in Rats without Affecting Hippocampal Brain‐Derived Neurotrophic Factor Protein Levels

Abstract: A growing body of evidence has pointed to the blockade of the N‐methyl‐d ‐aspartate (NMDA) receptor signaling as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with ketamine and imipramine in rats. To this aim, rats were 14 days treated once a day with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open‐field tests. Ketamine and imipramine, at the all doses tested, reduced immobility time, and increased both climbing and swimming time of rats compared to the saline group, without affecting spontaneous locomotor activity. Brain‐derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine‐ and ketamine‐treated rats by ELISA sandwich assay. Chronic administration of both drugs, ketamine and imipramine, did not modify BDNF protein levels in the rat hippocampus. In conclusion, our findings demonstrate for the first time that chronic administration of acute inactive doses of ketamine (5 mg/kg) becomes active after chronic treatment, while no signs of tolerance to the behavioural effects of ketamine were observed after chronic administration of acute active doses (10 and 15 mg/kg). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of mood disorders.     

Thiram and ziram stimulate non-selective cation channel and induce apoptosis in PC12 cells

The neurotoxicity of dithiocarbamates has been previously reported, however, the detailed mechanism underlying the neurotoxicity is still not fully understood. Among the dithiocarbamates, we investigated thiram and ziram in a neuronal-like pheochromocytoma (PC12) cells. Thiram and ziram strongly induced cell death in both dose- and time-dependent manners with the LC(50) of 0.3 and 2 microM, respectively. The cell death showed typical apoptotic features, such as DNA fragmentation and an increase of subdiploidy nuclei. Interestingly, both thiram and ziram induced rapid and sustained increases of intracellular Ca(2+) in PC12 cells, which were almost completely blocked by flufenamic acid (FFA), an inhibitor of non-selective cation channel. BAPTA-AM, an intracellular Ca(2+) chelator, inhibited the thiram- and ziram-induced apoptotic cell death. These results suggest that thiram and ziram induce apoptotic neuronal cell death by Ca(2+) influx through non-selective cation channels. The present study may provide a clue for understanding the mechanism of neurotoxicity of thiram and ziram.     

Bereavement-related cognitive impairment in an oldest-old community-dwelling Brazilian sample

As it is already known that depression can cause a demonstrable impact on cognition in elderly subjects, the objective of this study was to determine whether also the mourning process is associated with any cognitive impairment in this age range. A random and representative sample (a sample with 77 subjects/total county population of oldest-old with 219 subjects = 35%) aged 80 years or more was selected from the county of Veranópolis in the Brazilian rural southern region. Of this group, the cognitive function of subjects without grief and of subjects with the presence of grief were compared. Five neuropsychological tests (the Buschke-Fuld Selective Reminding Test, the word-list from the CERAD battery, the Verbal Fluency Test, and two subtests of the Wechsler memory scale), the Mini-Mental State Examination (MMSE) and two self-perceived memory impairment questionnaires were used. Presence of depressive symptomatology was identified by the Yesavage Geriatric Depression Scale (GDS). The prevalence rates of some psychiatric diagnoses (syndromic general anxiety disorder, major and minor depression) were compared between the bereaved group and the control group. There was not a statistically significant difference between the scores of controls and subjects with grief in the GDS. The frequency of affective disorders in both groups did not differ. However, the recently bereaved elderly subjects presented a mild cognitive impairment when evaluated with the MMSE, with the digit span test and with Word-list neuropsychological memory test. Likewise these bereaved octogenarian subjects presented more frequently a diagnosis of 'aging-associated cognitive decline' when compared with non-bereaved oldest-old. These results suggest that the normal sadness and/or the chronic stress of the grieving process, even without the presence of an identifiable syndromal-level depression, are associated with memory and cognitive differences among the bereaved oldest-old. Cause-effect relationships, however, cannot be established from this cross-sectional correlational study: Grief may influence cognitive functioning in the elderly, but mildly cognitively compromised elderly persons may be more likely to experience strong grief reactions after loss.     

Relapsed and late-onset Nipah encephalitis

An outbreak of infection with the Nipah virus, a novel paramyxovirus, occurred among pig farmers between September 1998 and June 1999 in Malaysia, involving 265 patients with 105 fatalities. This is a follow-up study 24 months after the outbreak. Twelve survivors (7.5%) of acute encephalitis had recurrent neurological disease (relapsed encephalitis). Of those who initially had acute nonencephalitic or asymptomatic infection, 10 patients (3.4%) had late-onset encephalitis. The mean interval between the first neurological episode and the time of initial infection was 8.4 months. Three patients had a second neurological episode. The onset of the relapsed or late-onset encephalitis was usually acute. Common clinical features were fever, headache, seizures, and focal neurological signs. Four of the 22 relapsed and late-onset encephalitis patients (18%) died. Magnetic resonance imaging typically showed patchy areas of confluent cortical lesions. Serial single-photon emission computed tomography showed the evolution of focal hyperperfusion to hypoperfusion in the corresponding areas. Necropsy of 2 patients showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigens but no evidence of perivenous demyelination. We concluded that a unique relapsing and remitting encephalitis or late-onset encephalitis may result as a complication of persistent Nipah virus infection in the central nervous system.     

Ceramide induces mitochondrial activation and apoptosis via a Bax-dependent pathway in human carcinoma cells

The intracellular pathways leading to mitochondrial activation and subsequent cell death in the ceramide-mediated stress response have been intensively studied in recent years. Experimental evidence has been provided that ceramide-induced apoptosis is inhibited by overexpression of antiapoptotic proteins of the Bcl-2 family. However, the direct effect of proapoptotic gene products, e.g. Bax, on ceramide-induced death signalling has not yet been studied in detail. In the present work, we show by measurement of mitochondrial permeability transition, cytochrome c release, activation of caspase-3 and DNA fragmentation that ceramide-induced apoptosis is marginal in Bax-negative DU 145 cells. Reconstitution of Bax by generation of DU 145 cells stably expressing this proapoptotic factor, clearly enhanced ceramide-induced apoptosis at all levels of the mitochondrial signalling cascade. Using the broad-range caspase inhibitor zVAD-fmk and zDEVD-fmk, an inhibitor of caspase-3-like activities, we demonstrate that the ceramide-induced mitochondrial activation in Bax-transfected DU 145 cells is caspase-independent. On the other hand, apoptotic events located downstream of the mitochondria, e.g. DNA fragmentation, were shown to be caspase-dependent. This influence of Bax on ceramide-induced apoptosis was confirmed in another cellular system: whereas Bax-positive HCT116 wild type cells were very sensitive towards induction of cell death by C(2)-ceramide, sensitivity of Bax knock-out HCT116 cells was significantly reduced. Thus, we conclude that Bax is a key activator of ceramide-mediated death pathways.     

Oral transmission of Chagas disease: importance of Trypanosoma cruzi biodeme in the intragastric experimental infection

Oral transmission of Trypanosoma cruzi has been suspected when epidemic episodes of acute infection were observed in areas devoid of domiciled insect vectors. Considering that the distribution of T. cruzi biodemes differs in sylvatic and domestic cycles, results of studies on biodemes can be of interest regarding oral transmission. The infectivity of T. cruzi strains of different biodemes was tested in mice subjected to infection by the digestive route (gavage). Swiss mice were infected either with the Peruvian strain (Biodeme Type I, Z2b) or the Colombian strain (Biodeme Type III, Z1, or T. cruzi I); for control, intraperitoneal inoculation was performed in a group of mice. The Colombian strain revealed a similar high infectivity and pathogenicity when either route of infection was used. However, the Peruvian strain showed contrasting levels of infectivity and pathogenicity, being high by intraperitoneal inoculation and low when the gastric route was used. The higher infectivity of the Colombian strain (Biodeme Type III) by gastric inoculation is in keeping with its role in the epidemic episodes of acute Chagas disease registered in the literature, since strains belonging to Biodeme III are most often found in sylvatic hosts.